A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
Phase: PHASE1
Conditions: Urothelial Carcinoma
Sponsor: Janssen Research & Development, LLC

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Approved, Date: 11 July 2022
Janssen Research & Development *
Clinical Protocol
A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and 
Pharmacodynamics of Various Regimens of Erdafitinib in Subjects with Metastatic or 
Locally Advanced Urothelial Cancer
Protocol 42756493BLC2002; Phase 1b-2
AMENDMENT 5
JNJ-42756493 (erdafitinib) and JNJ-63723283 (cetrelimab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen Pharmaceutica NV; Janssen, Inc; Janssen
Sciences Ireland UC; 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: 2017-001980-19
Status:
Approved
Date:
11 July 2022
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-ERI-148605285, 8.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT03473743

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MAIN TABLE OF CONTENTS
MAIN TABLE OF CONTENTS ..................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF APPENDICES................................................................................................................................ 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
PROTOCOL AMENDMENTS....................................................................................................................... 7
SYNOPSIS.................................................................................................................................................. 42
TIME AND EVENTS SCHEDULE .............................................................................................................. 48
ABBREVIATIONS ...................................................................................................................................... 49
1.
INTRODUCTION................................................................................................................................ 52
1.1.
Urothelial Bladder Cancer.............................................................................................................. 52
1.2.
FGFR Signaling.............................................................................................................................. 53
1.3.
Erdafitinib ....................................................................................................................................... 54
1.4.
PD-1/PD-L1 Signaling.................................................................................................................... 57
1.5.
Cetrelimab...................................................................................................................................... 57
1.5.1.
Summary of Nonclinical Data ..................................................................................................... 57
1.5.2.
Summary of Clinical Data ........................................................................................................... 58
1.6.
Platinum Chemotherapy in Metastatic Urothelial Cancer .............................................................. 62
1.7.
Overall Rationale for the Study...................................................................................................... 63
1.8.
Anticipated Benefits and Risks ...................................................................................................... 67
1.8.1.
Anticipated Benefits and Risks for Erdafitinib and Cetrelimab ................................................... 67
1.8.2.
Anticipated Benefits and Risks for Platinum Chemotherapy...................................................... 69
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 70
2.1.
Objectives and Endpoints .............................................................................................................. 70
2.2.
Hypotheses .................................................................................................................................... 71
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 71
3.1.
Overview of Study Design.............................................................................................................. 71
3.1.1.
Phase 1b..................................................................................................................................... 73
3.1.2.
Phase 2....................................................................................................................................... 75
3.1.3.
Schedule of Activities for All Ongoing Subjects After the End of Study Data Collection 
Timepoint (Protocol Amendment 5)............................................................................................ 75
3.2.
Study Design and Starting Dose Rationale.................................................................................... 75
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D..................................................... 78
3.3.1.
Definition of Dose-Limiting Toxicity for Phase 1b (Dose Escalation) ......................................... 78
3.3.2.
Determination of the Phase 1b RP2D Regimen and Alternative Dosing Schedules ................. 79
3.4.
Study Evaluation Team.................................................................................................................. 79
4.
SUBJECT POPULATION.................................................................................................................. 79
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 80
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 80
6.1.
Dose Combination Cohorts/Arms .................................................................................................. 80
6.2.
Administration of Erdafitinib ........................................................................................................... 80
6.2.1.
Dose Up-titration Guidelines....................................................................................................... 81
6.2.2.
Dose Modification, Dose Delays, and Retreatment Criteria for Erdafitinib................................. 81
6.2.3.
Guidance for Specific Erdafitinib Toxicities ................................................................................ 83
6.2.3.1.
Grading of Hyperphosphatemia and Nail Disorders................................................................ 83

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6.2.3.2.
Guidelines for the Management of Elevated Phosphate Levels ............................................. 83
6.2.3.3.
Guidelines for the Management of Dry Mouth and Stomatitis................................................. 85
6.2.3.4.
Guidelines for the Management of Dry Skin and Skin Toxicity ............................................... 87
6.2.3.5.
Guidelines for Management of Nail Toxicity (Onycholysis, Onychodystrophy, and 
Paronychia).............................................................................................................................. 87
6.2.3.6.
Guidelines for Eye Toxicity Associated With Vision Changes................................................. 89
6.2.3.7.
Guidelines for the Management of Dry Eye ............................................................................ 91
6.3.
Administration of Cetrelimab.......................................................................................................... 91
6.3.1.
Retreatment Criteria for Cetrelimab............................................................................................ 92
6.3.2.
Dose Delay for Cetrelimab.......................................................................................................... 93
6.3.3.
Cetrelimab Associated Toxicities Leading to Discontinuation of Study Treatment .................... 93
6.3.4.
Guidelines for Management of Immune-Related Adverse Events and Adverse Events 
of Clinical Interest ....................................................................................................................... 94
6.3.4.1.
Gastrointestinal Adverse Events ............................................................................................. 95
6.3.4.2.
Hepatic Adverse Events .......................................................................................................... 95
6.3.4.3.
Endocrinopathies..................................................................................................................... 96
6.3.4.4.
Rash ........................................................................................................................................ 97
6.3.4.5.
Renal Adverse Events ............................................................................................................. 98
6.3.4.6.
Neurological Adverse Events .................................................................................................. 98
6.3.4.7.
Pulmonary Adverse Events ..................................................................................................... 99
6.3.4.8.
Uveitis and Visual Complaints................................................................................................. 99
6.3.4.9.
Lipase/Amylase Elevations.................................................................................................... 100
6.3.4.10.
Infection ................................................................................................................................. 100
6.3.4.11.
Treatment of Anti-PD-1 Infusion-related Reactions............................................................... 100
6.3.4.12.
Monitoring During and After Study Drug Administration ....................................................... 101
6.4.
Administration of Platinum Chemotherapy (Cisplatin or Carboplatin) ......................................... 101
6.5.
Toxicity Due to One Study Drug and Continuation of Treatment ................................................ 101
7.
TREATMENT COMPLIANCE.......................................................................................................... 101
8.
CONCOMITANT THERAPY............................................................................................................ 102
8.1.
Permitted Medications.................................................................................................................. 102
8.2.
Prohibited Medications and Therapy ........................................................................................... 103
8.3.
Precautions for Concomitant Medications, Food, and Surgical Intervention............................... 104
9.
STUDY EVALUATIONS .................................................................................................................. 105
9.1.
Study Procedures......................................................................................................................... 105
9.1.1.
Overview................................................................................................................................... 105
9.1.2.
Screening Phase ...................................................................................................................... 105
9.1.3.
Treatment Phase ...................................................................................................................... 107
9.1.4.
Follow-Up Phase ...................................................................................................................... 108
9.2.
Efficacy Evaluations..................................................................................................................... 108
9.2.1.
Efficacy Endpoints .................................................................................................................... 109
9.2.2.
Treatment After Initial Disease Progression............................................................................. 109
9.3.
Pharmacokinetics and Immunogenicity ....................................................................................... 110
9.4.
Pharmacodynamic Evaluations.................................................................................................... 111
9.5.
Predictive and Exploratory Biomarkers........................................................................................ 111
9.6.
Safety Evaluations ....................................................................................................................... 113
9.6.1.
Adverse Events......................................................................................................................... 113
9.6.2.
Clinical Laboratory Tests .......................................................................................................... 114
9.6.3.
Renal Toxicity Evaluation ......................................................................................................... 115
9.6.4.
Urine or Serum Beta-hCG Pregnancy Test.............................................................................. 115
9.6.5.
Electrocardiogram..................................................................................................................... 115
9.6.6.
Echocardiography or MUGA Scan ........................................................................................... 115
9.6.7.
Ophthalmic Examination........................................................................................................... 115
9.6.8.
Vital Signs................................................................................................................................. 116
9.6.9.
Physical Examination................................................................................................................ 116
9.6.10.
ECOG Performance Status ...................................................................................................... 116

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9.6.11.
Documentation of Hearing Loss ............................................................................................... 116
9.7.
Sample Collection and Handling.................................................................................................. 117
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ......................................................................................................................... 117
10.1.
Completion ................................................................................................................................... 117
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study ................................................. 117
10.3.
Withdrawal From the Use of Research Samples......................................................................... 118
11.
STATISTICAL METHODS............................................................................................................... 118
11.1.
Sample Size Determination ......................................................................................................... 119
11.1.1.
Sample Size - Phase 1b ........................................................................................................... 119
11.1.2.
Sample Size - Phase 2 ............................................................................................................. 119
11.2.
Dose Escalation (Phase 1b) ........................................................................................................ 120
11.3.
Analysis Populations.................................................................................................................... 120
11.4.
Efficacy Analyses (Phase 2 Only)................................................................................................ 120
11.5.
Pharmacokinetic Analyses........................................................................................................... 121
11.6.
Immunogenicity Analyses ............................................................................................................ 121
11.7.
Pharmacodynamic Analyses, and Biomarker Analyses .............................................................. 121
11.8.
Pharmacokinetic/Pharmacodynamic Analyses............................................................................ 122
11.9.
Safety Analyses ........................................................................................................................... 122
11.10.
Data Review Committee .............................................................................................................. 123
12.
ADVERSE EVENT REPORTING .................................................................................................... 123
12.1.
Definitions .................................................................................................................................... 124
12.1.1.
Adverse Event Definitions and Classifications ......................................................................... 124
12.1.2.
Attribution Definitions................................................................................................................ 125
12.1.3.
Severity Criteria ........................................................................................................................ 125
12.2.
Special Reporting Situations........................................................................................................ 126
12.3.
Procedures................................................................................................................................... 126
12.3.1.
All Adverse Events.................................................................................................................... 126
12.3.2.
Serious Adverse Events ........................................................................................................... 128
12.3.3.
Disease-related Events or Outcomes Not Qualifying as Adverse Events or Serious 
Adverse Events......................................................................................................................... 129
12.3.4.
Pregnancy................................................................................................................................. 129
12.4.
Contacting Sponsor Regarding Safety......................................................................................... 130
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 130
13.1.
Procedures................................................................................................................................... 130
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 130
14.
STUDY DRUG INFORMATION....................................................................................................... 130
14.1.
Physical Description of Study Drug(s) ......................................................................................... 130
14.2.
Packaging .................................................................................................................................... 131
14.3.
Labeling........................................................................................................................................ 132
14.4.
Preparation, Handling, and Storage............................................................................................. 132
14.5.
Drug Accountability ...................................................................................................................... 132
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 133
16.
ETHICAL ASPECTS ....................................................................................................................... 133
16.1.
Study-Specific Design Considerations......................................................................................... 133
16.2.
Regulatory Ethics Compliance..................................................................................................... 134
16.2.1.
Investigator Responsibilities ..................................................................................................... 134
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 134
16.2.3.
Informed Consent ..................................................................................................................... 136
16.2.4.
Privacy of Personal Data .......................................................................................................... 137
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 137

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16.2.6.
Country Selection ..................................................................................................................... 137
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 138
17.1.
Protocol Amendments.................................................................................................................. 138
17.2.
Regulatory Documentation .......................................................................................................... 138
17.2.1.
Regulatory Approval/Notification .............................................................................................. 138
17.2.2.
Required Prestudy Documentation........................................................................................... 138
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 139
17.4.
Source Documentation................................................................................................................. 139
17.5.
Case Report Form Completion .................................................................................................... 140
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 141
17.7.
Record Retention ......................................................................................................................... 141
17.8.
Monitoring .................................................................................................................................... 142
17.9.
Study Completion/Termination..................................................................................................... 142
17.9.1.
Study Completion/End of Study................................................................................................ 142
17.9.2.
Study Termination..................................................................................................................... 143
17.10.
On-Site Audits .............................................................................................................................. 143
17.11.
Use of Information and Publication.............................................................................................. 144
REFERENCES WITHIN MAIN BODY OF THE PROTOCOL .................................................................. 146
INVESTIGATOR AGREEMENT ............................................................................................................... 249
LIST OF ATTACHMENTS
Attachment 1:
mTPI-2 Dose-finding Design........................................................................................ 149
Attachment 2:
Hepatitis B Virus Screening ......................................................................................... 150
Attachment 3:
Eastern Cooperative Oncology Group Performance Status Grade............................. 151
Attachment 4:
Drugs Classified as Strong CYP3A4 Inhibitors, Moderate to Strong CYP3A4 
Inducers, Moderate CYP2C9 Inhibitors, and Moderate CYP2C9 Inducers............................ 152
Attachment 5:
Amsler Grid .................................................................................................................. 153
Attachment 6:
The Stages of Heart Failure – New York Heart Association (NYHA) 
Classification........................................................................................................................... 154
Attachment 7:
Anticipated Events ....................................................................................................... 155
Attachment 8:
Cockcroft-Gault Formula for Estimated Creatinine Clearance (CrCl).......................... 157
Attachment 9:
RECIST GUIDELINES................................................................................................. 158
Attachment 10:
Guidance on Study Conduct During a National Disaster for Enrolled Subjects .......... 162
LIST OF APPENDICES
APPENDIX 1:
PHASE 1B ERDAFITINIB + CETRELIMAB................................................................. 164
APPENDIX 2:
PHASE 1B ERDAFITINIB+ CETRELIMAB + PLATINUM (CISPLATIN OR 
CARBOPLATIN) CHEMOTHERAPY...................................................................................... 190
APPENDIX 3:
PHASE 2 ERDAFITINIB +/ -CETRELIMAB COHORT ................................................ 222
APPENDIX 4: 
SUGGESTED SCHEDULE OF ACTIVITIES FOR PHASE 1B AND PHASE 2 
COHORTS FOLLOWING AMENDMENT 5............................................................................ 247

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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Best Overall Response – Investigator Assessment (8 mg QD) (Study 42756493-
BLC2001).................................................................................................................................. 55
Table 2:
Overall Summary of Treatment Emergent Adverse Events (TEAEs); Treated Subjects 
(Study 42756493-BLC2001) ..................................................................................................... 56
Table 3:
Potential Risks and Mitigation Strategies Associated With Erdafitinib and Cetrelimab............ 69
Table 4:
Molecular Eligibility Based Upon the Following FGFR Alterations a, b ...................................... 71
Table 5:
Erdafitinib Dose Modification Rules Based on Toxicity a .......................................................... 82
Table 6:
Dose Schedule and Dose Reductions for Erdafitinib................................................................ 83
Table 7:
Grading of Hyperphosphatemia and Nails Adverse Events ..................................................... 83
Table 8:
Guidelines for Management of Serum Phosphate Elevation.................................................... 84
Table 9:
Guidelines for the Management of Dry Mouth (Xerostomia) .................................................... 85
Table 10:
General Prophylaxis and Guidelines for the Management of Oral Mucositis........................... 86
Table 11:
Guidelines for Management of Dry Skin................................................................................... 87
Table 12:
General Prophylaxis & Guidelines for Management of Nail Discoloration/Loss/Ridging 
(Onycholysis/Onychodystrophy) ............................................................................................... 88
Table 13:
Guidelines for Management of Paronychia .............................................................................. 89
Table 14:
Guidelines for Management of Eye Toxicity ............................................................................. 90
Table 15:
Retreatment Criteria for Cetrelimab.......................................................................................... 92
Table 16:
Management of Immune-Related Gastrointestinal Adverse Events......................................... 95
Table 17:
Management of Immune-Related Hepatic Adverse Events...................................................... 96
Table 18:
Management of Immune-Related Endocrinopathies ................................................................ 96
Table 19:
Management of Rash................................................................................................................ 97
Table 20:
Management of Renal Adverse Events .................................................................................... 98
Table 21:
Management of Neurological Adverse Events ......................................................................... 98
Table 22:
Management of Pulmonary Adverse Events ............................................................................ 99
Table 23:
Management of Uveitis and Visual Complaints ........................................................................ 99
Table 24:
Management of Infusion-Related Reactions .......................................................................... 100
Table 25: Prohibited Concomitant Medications and Therapies4............................................................. 103
Table 26:
Concomitant Medications and Surgical Interventions to be Avoided or to be Used With 
Caution.................................................................................................................................... 104
FIGURES
Figure 1: Overview of the Phase 1b: Erdafitinib + Cetrelimab Cohort........................................................ 73
Figure 2: Overview of the Phase 1b: Erdafitinib + Cetrelimab + Platinum Chemotherapy Cohort............. 74
Figure 3: Overview of the Phase 2: Erdafitinib +/- Cetrelimab Cohort........................................................ 75

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PROTOCOL AMENDMENTS
Protocol Version 
Issue Date
Original Protocol
08 Dec 2017
Amendment 1
22 Jan 2018
Amendment 2
30 May 2019
Amendment 3
26 Jun 2020
Amendment 4
Amendment 5
08 Apr 2021
06 July 2022
Amendments below are listed beginning with the most recent amendment.
Amendment 5 (06 July 2022)
Overall Rationale for the Amendment: The overall reason for the amendment is to transfer all remaining subjects 
on study treatment to a new visit schedule with reduced data collection (Appendix 4) once the end of study data 
collection timepoint has been achieved. In addition, specifications for the primary efficacy analysis have been updated 
to align with the statistical analysis plan, and the priorities of the erdafitinib clinical development program.  
Section Number
and Name
Description of Change
Brief Rationale
Synopsis
Time and Events Schedule
3.1.3 Schedule of Activities for All 
Ongoing Subjects After the End of 
Study Data Collection Timepoint 
(Protocol Amendment 5),
Appendix 4 Table 1
12.3.1 All Adverse Events
A schedule of activities for all ongoing subjects 
after the end of study data collection timepoint has 
been added for subjects in Phase 1b and Phase 2.
To reduce the 
burden of study 
procedures not 
deemed 
necessary on 
remaining 
subjects after the 
end of study data 
collection.
6.2.3.6. Guidelines for Eye Toxicity 
Associated with Vision Changes
6.3.3. Cetrelimab Associated Toxicity 
Leading to Discontinuation of Study 
Treatment
8.CONCOMITANT THERAPY
9. STUDY EVALUATIONS 
9.1.3. Treatment Phase
9.1.4. Follow-up Phase
9.2 Efficacy Evaluations
9.3 Pharmacokinetics and 
Immunogenicity
9.6 Safety Evaluations
10. SUBJECT 
COMPLETION/DISCONTINUATION 
OF STUDY 
TREATMENT/WITHDRAWAL 
FROM STUDY
12.3.1. Adverse Events
17.9.1 Study Completion/End of Study
Following approval of Amendment 5, the eCRF 
and clinical database will be closed. All SAE 
reporting and concomitant therapies associated 
with an SAE will occur through the Company 
Safety Repository. No Pk samples will be 
collected. An ad-hoc sample for immunogenicity 
may be collected if required.
To reduce the 
burden of study 
procedures not 
deemed 
necessary on 
remaining 
subjects after the 
end of study data 
collection.
Synopsis,
11.4 Efficacy Analyses (Phase 2 Only)
The primary efficacy analysis will occur within ~6 
months of follow-up from last patient enrolled or 
sooner (if last patient discontinued prior to the 6-
month follow-up). This will be the final analysis 
for the study.
Alignment with 
the Statistical 
Analysis Plan, 
which allows for 
longer follow-up 
for a more robust 

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Section Number
and Name
Description of Change
Brief Rationale
The IRRC review has been removed.
assessment of 
efficacy. 
6.3.1 Retreatment Criteria for 
Cetrelimab
6.3.2. Dose Delay for Cetrelimab
6.3.3. Cetrelimab Associated Toxicities 
Leading to Discontinuation of Study 
Treatment
Added Grade ≤2 Hypothyroidism in the 
retreatment criteria of Table 15. Clarified Grade 
and definition of endocrinopathies leading to delay 
or discontinuation of cetrelimab.
To remove 
discrepancy of 
the definition 
between 
retreatment, 
delay and 
discontinuation 
of cetrelimab 
with respect to 
endocrinopathies.
6.3.4.2 Hepatic Adverse Events
The following text has been added:
Subjects who have a predominant cholestatic 
pattern of liver injury (dominant increase in ALP 
relative to ALT /AST) should be further evaluated 
to exclude a diagnosis of treatment emergent 
sclerosing cholangitis. An evaluation may include 
ultrasound of liver, cholangiography and referral 
to gastroenterologist and/or a hepatologist.
Belgian health 
authority 
requirement for 
sclerosing 
cholangitis.
9.6.2. Clinical Laboratory Tests
Updated the footnote about fasting glucose results 
to:
If fasting glucose results are available and meet the 
retreatment criteria, the HbA1c result does not need 
to be reviewed prior to dosing but should still be 
collected.
To clarify the 
meaning of the 
footnote.
Appendix 1 Table 1, Appendix 2 Table 
1,
Appendix 3 Table 1
The following changes are in reference to patients 
ongoing tumor assessment until Amendment 5 is 
approved:
Disease evaluations have been changed so that
after week 48 (± 3 days), then every 12 to 24 
weeks (± 14 days) until disease progression.
Labs prior to the D15 cetrelimab dose can be 
obtained up to 2 days prior. 
To reduce the 
amount of study 
procedures for 
subjects who are 
on study for 
longer than 1 
year. 
10.1 Completion
12.3.1. All Adverse Events
17.9.1. Study Completion/End of Study
Definition of subject completion and end of study 
has been updated.
To reduce the 
burden of study 
procedures and 
data collection 
once the primary 
efficacy analysis 
data cutoff is 
achieved.
Throughout protocol
Minor corrections for clarification.
Clarifications

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Amendment 4 (08 April 2021)
Overall Rationale for the Amendment: The overall reason for the amendment is to allow local prospective FGFR 
testing in addition to local historical testing (archived sample) to facilitate more rapid determination of molecular 
eligibility. Furthermore, the requirement for paired biopsies was removed. An adjustment to eligibility criteria relating 
to creatinine clearance (CrCl) was made to align Phase 1b and Phase 2 of the study for cisplatin-ineligibility and 
eligibility. In addition, other corrections and clarifications were made as detailed in the table below.
Section 
Number
and Name
Description of Change
Brief Rationale
9.1.2. 
Screening 
Phase, 
Appendix 1 
Table 1, 
Appendix 2 
Table 1, 
Appendix 3 
Table 1
Removal of reference to historical testing:
Local historical test results
Clarification 
that 
local 
prospective FGFR testing 
as well as local historical 
testing is permitted and 
that biopsy samples may 
be archival or fresh tissue 
samples
Subjects enrolling based on local historical testing must submit 
archival or fresh tumor tissue
Update relating to paired biopsies (for tables, text in Footnote “g”):
Paired biopsies at Screening and C2D1 are optional. The biopsy 
upon PD is also optional for all subjects. For subjects enrolling in the 
Phase 1b DL2B and Phase 2 Arm A cohorts, paired biopsies will be 
required (where local regulations permit and if the tumor is accessible) 
at Screening and C2D1 prior to erdafitinib administration (biopsy 
cohort). High-risk areas of metastases such as brain, pancreas, and lung 
should not be considered as an accessible site for biopsy. Biopsies will 
be collected to aim to have a minimum of 15 evaluable biopsy pairs 
(total from Phase 1b DL2B and Phase 2 Arm A cohorts). Exceptions 
may apply upon discussion between the investigator and medical 
monitor.
Removal of requirement of 
paired 
biopsies 
and 
clarification 
that, 
for 
cohorts other than Phase 
1b DL2B cohort (which is 
now fully enrolled), paired 
biopsies are optional.
Synopsis 
(Subject 
population), 
3.1. Overview 
of Study 
Design, 11.1.1. 
Sample Size -
Phase 1b, 
Appendix 2 
Section 3.1.1
Three wild type subjects (either wild-type or with select FGFR gene 
alterations) will be enrolled in the initial erdafitinib + cetrelimab + 
cisplatin dose level (50 mg/m2). If the starting dose is safe, 3
6 additional wild type subjects and 3 additional subjects with select 
FGFR gene alterations will be enrolled into the escalated dose of 
cisplatin (60 mg/m2). Out of 6 subjects, up to 3 subjects can be wild-
type and the other subjects should be with select FGFR gene 
alterations. Approximately 10 additional subjects with select FGFR 
gene alterations will be enrolled at the maximum tolerated dose (MTD) 
for erdafitinib + cetrelimab + cisplatin.
Three wild type subjects (either wild-type or with select FGFR gene 
alterations) will be enrolled in the initial erdafitinib + cetrelimab + 
carboplatin dose level (AUC4 mg/mL/min). If the starting dose is safe, 
3 6 additional wild type subjects and 3 additional subjects with select 
FGFR gene alterations will be enrolled into the escalated dose of 
carboplatin (AUC5 mg/mL/min). Out of 6 subjects, up to 3 subjects 
can be wild-type and the other subjects should be with select FGFR 
gene alterations. Approximately 10 additional subjects with select 
FGFR gene alterations will be enrolled at the MTD for erdafitinib + 
cetrelimab + carboplatin.
Clarification 
on 
FGFR 
status of subjects enrolled 
into 
the 
chemotherapy 
cohorts.
Appendix 1, 
Section 4.1, 
Appendix 2 
Section 4.1, 
Exception for Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort: approximately 6 up to 3 subjects in each 
erdafitinib + cetrelimab + chemotherapy cohort at each dose level will 
be wild-type.

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and Name
Description of Change
Brief Rationale
Tables 8, 9, 
10, 13, and 14
In Table 8 (Guidelines for Management of Serum Phosphate 
Elevation), Grade 3 begin at 9.00 mg/dL (not >9.00 mg/dL). 
In Table 9 (Guidelines for the Management of Dry Mouth 
[Xerostomia]), Grade 3 management begins with “Hold study drug (for 
up to 28 days)” (removed the end phrase “discontinue if longer”). 
Added “orally” to medical management. 
In Table 10 (General Prophylaxis and Guidelines for the Management 
of Oral Mucositis), Grade 2 fifth bullet states “. . . then restart at 1 dose 
level below” (“below” was added). For symptom management, the last 
bullet now reads, “. . . and recommend appropriate anti-fungal or anti-
viral agents” (“recommend” added). Abbreviations added to footnotes.
In Table 13 (Guidelines for Management of Paronychia), in accordance 
with the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) Version 4.03, removed Grade 4. Also 
removed the definitions and column subheader now “Grade”. 
In Table 14 (Guidelines for Management of Eye Toxicity), Grade 2, 
fourth management paragraph now reads, “If toxicity is [removed 
“Grade 2 and” here] reversible . . .”. For Grade 3, first management 
sentence states, “ . . . report an SAE and withhold erdafitinib.” 
(Previously, stated “permanently discontinue erdafitinib”.)
Updated guidance for 
specific toxicities 
associated with 
erdafitinib  
6.3.1. 
Retreatment 
Criteria for 
Cetrelimab
Addition of footnote to Table 15:
If fasting glucose results are available and meet the retreatment 
criteria, the HbA1c result does not need to be reviewed prior to 
dosing, but should still be collected.
Clarification for fasting 
glucose requirements
9.1.2. 
Screening 
Phase
The following text added:
If a biopsy is required to perform FGFR analysis, the patient
subject must consent to this procedure utilizing the main study 
consent form.
To provide clarification 
on consent for biopsy
9.1.2. 
Screening 
Phase
The following text was updated:
Local historical test results (from tissue or blood) or the Qiagen 
Therascreen FGFR RGQ RT-PCR test (from tissue) performed at a 
CLIA-certified or regional equivalent laboratory using the following 
methods may be used to meet molecular eligibility.: local, direct digital 
counting methods, or the Qiagen Therascreen FGFR RGQ RT PCR 
test. A de identified copy of the test report documenting the FGFR 
result must be included in the participant subject records and a de-
identified copy must also be submitted to the sponsor for 
confirmation of eligibility.
To provide clarification 
on recording of local 
FGFR test results
9.1.2. 
Screening 
Phase
The following text added:
Concordance between local and central testing, where applicable, 
will be reviewed periodically by the sponsor.
Added clarification that 
concordance 
between 
local and central testing 
will be reviewed.
9.2. Efficacy 
Evaluations
Rewording as follows:
The site will send all radiographic scans for all patients subjects 
randomized to Phase 2 to a central vendor for possible future 
independent assessment to confirm the response, if needed.
Clarified this text refers 
to subjects randomized 
to Phase 2.
9.3. Pharmaco-
kinetics and 
Immuno-
genicity
The following text added:
Post-dose blood samples should be drawn after both the drug 
infusion and the post-infusion flush have been completed.
To 
ensure 
correct 
timing of post-infusion 
PK blood sample
9.5. Predictive 
and 
Exploratory 
Biomarkers
The following sentence was amended:
Adjustments in the timing of biomarker collections may be made or 
collections may be stopped during the study based on emerging data.
To 
clarify 
that 
biomarker 
collection 
may be stopped once 

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Description of Change
Brief Rationale
sufficient biopsies have 
been obtained.
9.6.2. Clinical 
Laboratory 
Tests
Alkaline phosphatase, fasting glucose, and HbA1c testing (additional 
explanation and detail was added for the glucose and HbA1c tests) were 
added to the Serum Chemistry Panel. “Total” was removed from 
amylase. 
Addition of alkaline 
phosphatase, 
fasting 
glucose 
and 
HbA1c 
testing (at screening and 
as clinically indicated)
12.3.1. All 
Adverse 
Events
Update of language regarding AE collection:
All AEs and special reporting situations, whether serious or non-
serious, will be reported starting from the time a signed and dated Full-
Study ICF is obtained until 10030 days after the last dose of study drug
erdafitinib, and 100 days after the last dose of cetrelimab 
(whichever is longer). If the subject starts a subsequent systemic 
anticancer therapy, AE data collection will be limited to only Grade 2 
immune-related AEs (for patients subjects who received cetrelimab)
and all SAEs from the date the new anticancer therapy is initiated until 
30 days after the last dose of erdafitinib or 100 days after the last 
dose of cetrelimab, whichever is longer (see table below). The chart 
in this section was updated accordingly.
Clarification 
around 
timing of AE collection.
Appendix 1 
Table 1, 
Appendix 2 
Table 1, 
Appendix 3 
Table 1
Addition of the following for PO4, PTH, TSH, T3 and FT4:
May be obtained up to 2 days prior to Day 1 of each cycle: for exact 
assessments, see Section 9.6.2.
Aligning with wording 
for 
chemistry 
parameters
Appendix 1, 
Section 4.1, 
Appendix 2 
Section 4.1, 
Appendix 3 
Section 4.1
Thyroid panel: TSH, T3 or Free T3 (FT3) and Free thyroxine (FT4)
TSH previously omitted 
from heading in error
Appendix 1 
Table 2, 
Appendix 3 
Table 2
Update to footnote:
Pre-dose PK sample for erdafitinib and Pre-infusion PK and 
immunogenicity samples for cetrelimab may be collected up to 
1 hour30 minutes before dosing, respectively.
To ensure consistency 
with Section 9.3.
Appendix 1 
Table 2
Addition of footnote:
Cetrelimab PK is not required for alternative cohorts (alternative 
cohorts start cetrelimab on C2D1, e.g. DL2B).
To provide clarification 
that cetrelimab PK is 
not 
required 
for 
alternative cohorts 
Appendix 2 
Table 2
Addition of Cetrelimab PK and Cetrelimab Immunogenicity 
assessments at End-of-Treatment and Follow-up timepoints
Corrections made to 
PK, immunogenicity 
and biomarker sample 
timings
Appendix 2 
Table 2
Optional Tumor Biopsy for Biomarker Research assessments included 
in table for Full-study screening period, Treatment Cycle 2 Day 1, and 
End-of Treatment timepoint.
Appendix 3, 
Table 2
Addition of Cetrelimab PK assessment at Treatment Cycle 1, Day 15
Appendix 1 
Table 1, 
Appendix 2 
Table 1
CrCl is to be performed only at Screening and is calculated by the 
Cockcroft-Gault formula
Clarifications regarding 
timings of assessments
Appendix 2 
Table 2
Clarifications for Cetrelimab PK for Treatment Cycle 1, Days 8 and 15 
timepoints:

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Description of Change
Brief Rationale
X Any time during visit
Appendix 3, 
Table 1
Clarification that vital signs monitored pre-dose only for Arm A
Appendix 2 
Table 1
Addition of footnote:
Post-dose ECGs for subjects receiving platinum chemotherapy 
should be recorded as soon as possible upon completion of infusion 
on C2D1 and C4D1
11.1.2. Sample 
Size - Phase 2, 
11.4. Efficacy 
Analyses 
(Phase 2 Only)
Added the following clarification:
approximately 45 subjects results in a 95%
Text reworded for 
clarity
Synopsis 
(Statistical 
Methods), 
11.4. Efficacy 
Analyses 
(Phase 2 Only)
Added the following clarification:
approximately 90 response-evaluable subjects
6.2.3.3. 
Guidelines for 
the 
Management 
of Dry Mouth 
and Stomatitis 
Table 9
Rewording as follows:
Saline peroxide salt
9.14. Follow-
Up Phase
Rewording as follows:
All subjects who enter the Follow-up Phase will have a follow-up visit 
every 12 weeks (± 7 days) after the last dose of study treatment to 
assess survival status and assess start of alternate anticancer therapy 
data until death, the subject withdraws consent, or the end of study, 
whichever occurs first as outlined in the cohort-specific Time and 
Events Schedule.
Appendix 1 
Section 6.1
Rewording as follows:
Both study drugs should be held for If a AEs ≥Grade 3 AE is that are
not attributable to study treatment (erdafitinib or cetrelimab, or 
chemotherapy), or the disease under study (eg. immune related, 
hyperphosphatemia, nail toxicity, stomatitis, CSR), then all both
study drugs should be held.
Appendix 2, 
Section 6.4.3
Addition of text:
Routine primary prophylaxis to treat immunosuppression is not 
permitted for subjects
Appendix 1, 
Section 4.1, 
Appendix 2 
Section 4.1 
and Appendix 
3 Section 4.1
Rewording as follows:
Within normal institutional limits Below institutional ULN within 
14 days of treatment and prior to C1D1 (medical management allowed)
Appendix 2, 
Table 1
Treatment Cycle 3 g
Day 1 (±2)
Day 8 (±2)
Day 15 (±2)
Removal of columns as 
no study assessments 
performed at these 
timepoints
Appendix 1 
Table 2, 
Visit windows added to table header.
To add clarification on 
visit windows and to 

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Description of Change
Brief Rationale
Appendix 2 
Table 2, 
Appendix 3 
Table 2
align with Table 1 in 
each appendix.
Appendix 2, 
Section 3.1.1
Correction of cohorts:
Erdafitinib + cetrelimab + cisplatin (DL2C, or DL2C1, or DL2C2)
Typographical errors 
corrected
Amendment 3 
summary of 
changes
2.1. Objectives and Endpoints for Phase1b Phase 2
Note that in the Summary of Changes for Amendment 3, this was 
incorrectly noted in the subtitle for Section 2.1 Appendix 3 as Phase 1b 
rather than Phase 2. However, the subtitle in the body of the protocol 
is correct.
Amendment 3 
summary of 
changes
there are 110 approximately 90 response-evaluable subjects.
Note that in the Summary of Changes for Amendment 3, this was 
incorrectly noted as 110 rather than 90. However, the number in the 
body of the protocol is correct.
Throughout 
protocol
Minor corrections to spelling and cross references, addition of new 
references to reference list, and removal of reference numbering.
Amendment 3  26 Jun 2020
Overall Rationale for the Amendment: The overall reason for the amendment is to add a new cohort 
(erdafitinib + cetrelimab + platinum [cisplatin or carboplatin] chemotherapy) to the Phase 1b (Dose 
escalation) part of the study. As a result of adding this new cohort, the study title was revised and the layout 
of the protocol was reorganized to clarify inclusion/exclusion criteria, the Time and Events Schedule, 
toxicity management, and administrative changes for each cohort in respective appendices.
Section Number
and Name
Description of Change
Brief Rationale
Protocol Title page; 
Synopsis (Title)
The title of the protocol was updated to “A Phase 
1b-2 Study to Evaluate Safety, Efficacy, 
Pharmacokinetics, and Pharmacodynamics of 
Various Regimens of Erdafitinib in Subjects with 
Metastatic or Locally Advanced Urothelial 
Cancer”.
To accommodate for the expanded 
scope of treatment cohorts within 
this Phase 1b/2 study. 
Synopsis 
(Hypotheses); 2.2. 
Hypothesis for Phase 
1b Erdafitinib + 
Cetrelimab + 
Platinum 
Chemotherapy 
(Appendix 2)
The hypothesis was amended to include the 
Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort.
To describe the study hypothesis 
for the Phase 1b erdafitinib + 
cetrelimab + platinum
chemotherapy cohort.
2.1. Objectives and 
Endpoints for 
Phase1b (Appendix 2)
The primary objective of the Phase 1b erdafitinib + 
cetrelimab + platinum chemotherapy cohort was 
added to the study: “To characterize the safety and 
tolerability of erdafitinib in combination with 
cetrelimab and platinum (cisplatin or carboplatin) 
chemotherapy, and to identify the recommended 
Phase 2 dose(s) (RP2D) and schedule for 
erdafitinib with cetrelimab and platinum (cisplatin 
or carboplatin) chemotherapy”.
To describe the primary objectives 
and endpoints for the Phase 1b 
erdafitinib + cetrelimab + 
platinum chemotherapy cohort.

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and Name
Description of Change
Brief Rationale
2.1. Objectives and 
Endpoints for 
Phase1b (Appendix 1)
The primary objective of the Phase 1b erdafitinib + 
cetrelimab cohort was amended as follows: 
“To identify the RP2D and schedule of
erdafitinib in combination with 
cetrelimab”
“To characterize the safety and 
tolerability of erdafitinib in 
combination with cetrelimab, and to 
identify the recommended Phase 2 
dose(s) (RP2D) and schedule for 
erdafitinib”.
The primary endpoints for the Phase 1b erdafitinib 
+ cetrelimab cohort were amended as follows:

“Incidence of DLT”

“Incidence of AEs”

“Frequency and type of dose-
limiting toxicity (DLT)”.
To describe the change in the 
primary objectives and endpoints 
for the Phase 1b erdafitinib + 
cetrelimab cohort.
2.1. Objectives and 
Endpoints for 
Phase1b (Appendix 1)
The secondary endpoints for the Phase 1b 
erdafitinib + cetrelimab cohort were amended as 
follows:
“Plasma erdafitinib and serum cetrelimab 
concentrations”

“Population PK parameters and metrics of 
systemic exposure of erdafitinib and 
cetrelimab”

“Concentration and PK parameters of 
erdafitinib and cetrelimab”

“Detection of antibodies to cetrelimab and 
effects on serum cetrelimab levels”.
To describe the change in the 
secondary endpoints for the 
Phase 1b erdafitinib + cetrelimab 
cohort.
2.1. Objectives and 
Endpoints for 
Phase1b (Appendix 3)
The primary objective of the Phase 2 erdafitinib 
+/- cetrelimab cohort was amended as follows:
“To evaluate the safety and clinical activity 
of erdafitinib alone and in combination 
with cetrelimab in in first line mUC 
setting cisplatin-ineligible subjects with 
metastatic or locally advanced 
urothelial cancer with select FGFR 
gene alterations and no prior systemic 
therapy for metastatic disease”.
To describe the change in the 
primary objectives for the Phase 2 
erdafitinib + /-cetrelimab cohort.
2.1. Objectives and 
Endpoints for 
Phase1b (Appendix 3)
The following secondary endpoint for the Phase 2 
erdafitinib +/- cetrelimab cohort was deleted:

“Population PK parameters and metrics of 
systemic exposure of erdafitinib and 
cetrelimab”.
To describe the change in the 
secondary endpoints for the 
Phase 2 erdafitinib +/- cetrelimab 
cohort.
Synopsis (Title)
A description of the mechanism of action for 
cisplatin and carboplatin that will be utilized in the 
Phase 1b erdafitinib + cetrelimab + platinum
chemotherapy cohort was added below the study 
title. 
To support the rationale for the 
addition of the Phase 1b 
erdafitinib + cetrelimab + 
platinum chemotherapy cohort 
into this study.
1. Introduction
Text added to describe the rationale for adding the 
platinum chemotherapy cohort to the study. 

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Section Number
and Name
Description of Change
Brief Rationale
1.6. Platinum
Chemotherapy in 
Metastatic Urothelial 
Cancer
New section added to present safety, efficacy, PK 
and PD data regarding the use of cisplatin and 
carboplatin as standard of care agents in metastatic 
urothelial carcinoma.
1.7. Overall Rationale 
for the Study
New subsection entitled “Rationale for addition of 
platinum [cisplatin or carboplatin] chemotherapy 
to erdafitinib and cetrelimab)” was added. 
1.8.2. Anticipated 
Benefits and Risks for 
Platinum
Chemotherapy
New section added to describe the anticipated 
benefits and risks for platinum chemotherapy.
3.2. Study Design and 
Starting Dose 
Rationale
New subsection entitled “Rationale for 
Combination of Erdafitinib, Cetrelimab, and 
Platinum Chemotherapy” was added. Rationale for 
the Subject Population was also updated.
Synopsis (Overview 
of Study Design); 3.1. 
Overview of Study 
Design; 3.1.1. Phase 
1b
The overview of the study design was updated and 
Figure 2 was created to describe the platinum 
chemotherapy cohort.
To provide an overview of dose 
escalation strategy for the 
Phase 1b erdafitinib + cetrelimab 
+ platinum chemotherapy cohort.
Synopsis (Subject 
Population)
The description of the sample size was updated to: 
“A total of approximately 160 subjects will be 
enrolled in this study. Thirty subjects are 
planned to be enrolled in the Phase 1b 
erdafitinib + cetrelimab cohort. Forty subjects 
are planned to be enrolled in the Phase 1b 
erdafitinib + cetrelimab + platinum 
chemotherapy cohort. Ninety subjects are 
planned to be enrolled in the Phase 2 erdafitinib 
+/1 cetrelimab cohort”.
In addition, the subject population was defined as 
metastatic or locally advanced urothelial cancer.
To update the sample size and 
analysis of the Phase 1b and the 
Phase 2 cohort based upon the 
changes to the study objectives 
and endpoints as well as the 
addition of the Phase 1b 
erdafitinib+ cetrelimab + platinum 
chemotherapy cohort.
Synopsis (Statistical 
Methods)
The following updates were made to the Phase 2 
statistical methods: “In Phase 2, approximately 120
90 subjects will be assigned randomly in a 1:1 ratio 
to receive either erdafitinib monotherapy (Arm A) 
or erdafitinib and cetrelimab combination therapy 
(Arm B). With approximately 60 45 subjects on 
Arm A and assuming a true ORR of 45%, per 
arm, the study is designed such that the resulting 
95% confidence interval for estimating ORR 
excludes those less or equal to 30%. Similarly, 
assuming a true ORR of 55% in Arm B, 45 
subjects results in a 95% confidence interval 
that excludes ORR less or equal to 40%. to test 
the hypothesis null hypothesis (H0) of: ORR ≤30% 
vs. the alternative hypothesis (Ha) of: ORR ≥45% 
in Arm A and H0: ORR ≤30% vs. Ha: ORR ≥55% 
in Arm B. With 55 response evaluable subjects per 
arm, this design has 80% and 97% power at a Type 
I error rate of 0.1 and 0.05 (1 sided) for Arm A and 
B, respectively. A futility analysis will be 
conducted by the DRC after approximately 40 

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Brief Rationale
response evaluable subjects (refer to Statistical 
Analysis Plan for definition) have been obtained in 
Phase 2. enrolled and evaluated. The objective 
response rate will be calculated with a 90 95% 
confidence interval by each arm in the treated 
population according to the RECIST 1.1 criteria 
(Attachment 9)”.
11.1.2. Sample Size -
Phase 2
The following updates were made to the Phase 2 
statistical methods: “In Phase 2, approximately 120
90 subjects will be assigned randomly in a 1:1 ratio 
to receive either erdafitinib monotherapy (Arm A) 
or erdafitinib and cetrelimab combination therapy 
(Arm B).
1)
In the erdafitinib monotherapy arm (Arm 
A), ORR will be estimated using a 95% 
confidence interval. Assuming a true 
ORR of 45%, a sample size of 45 
response evaluable subjects will result in 
a 95% confidence interval that excludes 
those less than or equal to 30%. the 
following hypothesis will be tested: H0: 
ORR ≤30% vs. Ha: ORR ≥45%. With 55 
response evaluable subjects, this design has 
80% power at a Type I error rate of 0.1 (1
sided) when the true ORR is 45% in the 
monotherapy arm.
2)
In the erdafitinib and cetrelimab 
combination therapy (Arm B), ORR will 
be estimated using a 95% confidence 
interval. Assuming a true ORR of 55%, a 
sample size of 45 response evaluable 
subjects result in a 95% confidence 
interval that excludes ORR less or equal 
to 40%.” the following hypothesis will be 
tested: H0: ORR ≤30% vs. Ha: ORR ≥55%. 
With 55 response evaluable subjects, this 
design has 97% power at a Type I error rate 
of 0.05 (1 sided) when the true ORR is 
55% in the combination arm.
3)
Accounting for a 10% drop out rate, 
approximately 120 subjects will be 
enrolled”.
Synopsis (Statistical 
Methods); 11.4. 
Efficacy Analyses 
(Phase 2 only)
The trigger for the primary efficacy analysis was 
redefined as when there are 90 subjects. The final 
analysis will be performed after the end of the 
study.
Synopsis (Subject 
Population and 
Statistical Methods); 
3.1. Overview of 
Study Design; 3.1.2. 
Phase 2 (Figure 3); 
The total number of subjects enrolled in each 
treatment cohort was updated.

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Brief Rationale
11.1.1. Sample Size -
Phase 1b
11.4. Efficacy 
Analyses (Phase 2 
only)
The primary efficacy analysis was amended as 
follows: “The primary efficacy analysis is planned 
when the last subject enrolled has a minimum of 
6 months of follow up and the final analysis will 
be performed after the End of the Study there 
are110 90 response-evaluable subjects. The final 
analysis will be performed after the end of the 
study”.
The primary endpoint was amended as follows:
“Primary endpoint: ORR will be calculated
estimated with a 90 95% confidence 
interval. Response will be assessed by 
investigators and may be assessed by an 
Independent Radiologic Review 
Committee (IRRC).The primary efficacy 
analysis will be based on the response 
will be assessed by investigators. An 
IRRC will also review responses for 
Phase 2. The IRRC assessment of 
response will be used for the reporting 
of the primary endpoint if the primary 
objective is achieved by using the 
investigators’ assessments”.
6.4. Administration of 
Platinum
Chemotherapy 
(Cisplatin or 
Carboplatin)
(Appendix 2)
Added subsections that provide a description of 
cisplatin, carboplatin, antiemetic therapy and 
supportive care guidelines for platinum 
chemotherapy, supportive care guidelines for 
chemotherapy, dose modification, dose delays, 
retreatment criteria, guidance for specific platinum 
chemotherapy toxicities, and platinum 
chemotherapy associated toxicities leading to 
discontinuation of study treatment. 
To provide specific guidance to 
the site regarding the addition of 
the Phase 1b erdafitinib + 
cetrelimab + platinum 
chemotherapy cohort.
8.1. Permitted 
Medications
A list of permitted antiemetics and a clarification 
regarding primary prophylaxis were added.
The following sentence was amended: “In 
general, Ggrowth factor support is permitted for 
the management of treatment-emergent 
hematological toxicity as recommended according 
to National Comprehensive Cancer 
Network/European Organization for Research and 
Treatment of Cancer (NCCN/EORTC) guidelines. 
Primary prophylaxis is not permitted for 
subjects who are under evaluation for DLTs”.
8.2. Prohibited 
Medications and 
Therapy
Table describing the prohibited concomitant 
medications and therapies was updated.

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Section Number
and Name
Description of Change
Brief Rationale
14.1. Physical 
Description of Study 
Drug (s); 14.2. 
Packaging; 14.3. 
Labeling
Text regarding platinum (cisplatin or carboplatin)
chemotherapy was added.
Synopsis 
(Evaluations); 6.2.3.6. 
Guidelines for Eye 
Toxicity Associated 
with Vision Changes
Text updated to confirm that corneal or retinal 
abnormalities for subjects receiving erdafitinib are 
considered adverse events of special interest. 
These occurrences should be reported as adverse 
events or as serious adverse events if the severity is 
Grade 3 or higher and require enhanced reporting 
and data collection.
To provide guidance to the site 
staff regarding the potential 
adverse events associated with the 
Phase 1b erdafitinib + cetrelimab 
+ platinum chemotherapy cohort. 
Also, to provide additional 
guidance to the sites regarding the 
reporting of adverse events.
6.5. Toxicity Due to 
One Study Drug and 
Continuation of 
Treatment
The following updates were made: “The dose 
modification guidelines described in Section 6.2, 
and Section 6.3, and Section 6.4 are to be used 
throughout both phases of the study, as applicable. 
If a subject experiences several toxicities and 
there are conflicting recommendations, the 
most conservative dose adjustment 
recommended should be followed (dose 
reduction appropriate to the most severe 
toxicity). The recommendation to discontinue 
study therapy may apply to both all study drugs”.
Attachment 4
Title and content of attachment updated to “Drugs 
Classified as Strong CYP3A4 Inhibitors, Moderate 
to Strong CYP3A4 Inducers, Moderate CYP2C9 
Inhibitors, and Moderate CYP2C9 Inducers”. 
Attachment 7
Statement regarding platinum chemotherapy was 
added. Template language regarding reporting of 
anticipated events and the Safety Assessment 
Committee was added. 
1.5.2. Summary of 
Clinical Data; 3.2. 
Study Design and 
Starting Dose 
Rationale
Incorporated text from the Investigator Brochure 
regarding alternate dosing regimens for cetrelimab.
Established safety data supports 
the rationale to change the dose 
regimen of the cetrelimab in the 
Phase 1b and the Phase 2 cohorts.
Synopsis (Overview 
of Study Design, 
Dosage and 
Administration); 
3.1.1. Phase 1b 
(Figure 1); 3.1.2. 
Phase 2 (Figure 3); 
3.1.1. Phase 1b 
(Appendix 1); 3.1.2. 
Phase 2 (Appendix 3); 
6.1. Dose 
Combination for 
Erdafitinib +/-
Cetrelimab Cohorts 
(Appendix 1, 
Appendix 3); 6.3. 
Administration of 
Cetrelimab
The text was amended to describe the change in
the dosing regimen of cetrelimab from 
240 mg Q2W (Cycles 1-4) to 480 mg Q4W 
(starting at Cycle 5) for all dose levels within the 
Phase 1b erdafitinib + cetrelimab cohort and the 
Phase 2 erdafitinib +/- cetrelimab cohort. 

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Brief Rationale
6.3. Administration of 
Cetrelimab
To define the dose of cetrelimab as 360 mg IV 
Q3W in the erdafitinib + cetrelimab + platinum
chemotherapy cohort.
9.1.3. Treatment 
Phase
The following statement was amended: “The 
Treatment Phase will begin with the administration 
of the first dose of erdafitinib alone or in 
combination with cetrelimab +/- platinum
(cisplatin or carboplatin) chemotherapy and will 
continue until disease progression or unacceptable 
toxicity (based on Investigator assessment) 
occurs”.
Content updates to protocol text to 
increase the scope of the study to 
include the Phase 1b erdafitinib + 
cetrelimab + platinum 
chemotherapy cohort.
9.5. Predictive and 
Exploratory 
Biomarkers
The following statement was amended: “To further 
elucidate the erdafitinib mechanism of action, the 
effect of erdafitinib, or the erdafitinib plus 
cetrelimab combination, or the erdafitinib + 
cetrelimab + platinum chemotherapy 
combination on tumor immune cell infiltrate (and 
peripheral immune cells) will be assessed”.
11.5. Pharmacokinetic 
Analyses; 11.8. PK/ 
PD Analyses; 16.1. 
Study-Specific 
Design 
Considerations
Text added regarding the platinum chemotherapy 
cohort. 
3.2. Study Design and 
Starting Dose 
Rationale
Updated the following subsections in regard to the 
potential interactions between platinum 
chemotherapy and cetrelimab:
“Potential for PK-mediated drug-drug interaction”
“Potential for PD-mediated drug-drug interaction 
(serum phosphate)”.
To assess the impact of study 
drug(s) on safety, PK, and PD 
parameters due to the addition of 
the Phase 1b erdafitinib + 
cetrelimab + platinum 
chemotherapy cohort.
9.3. PK and 
Immunogenicity; 
Time and Events 
Schedules (Appendix 
1, Appendix 2, 
Appendix 3); PK, 
Immunogenicity, and 
Biomarker Sampling 
Tables (Appendix 1, 
Appendix 2, 
Appendix 3)
PK sampling times for the Phase 1b erdafitinib, 
cetrelimab, and the Phase 1b erdafitinib +
cetrelimab + platinum (cisplatin or carboplatin)
chemotherapy cohorts were updated/added. The 
PK, immunogenicity, and biomarker sampling text 
were removed from the Time and Events 
Schedules and placed in cohort-specific appendix 
tables. 
9.4. 
Pharmacodynamic 
Evaluations
The following text was amended: 
“Hypophosphatemia is a common adverse event 
of chemotherapy. Phosphate levels will be 
evaluated throughout the study as a PD and safety 
biomarker for erdafitinib. Serum for the 
assessment of phosphate concentrations will be 
collected as outlined in the cohort-specific Time 
and Events Schedule”.
Throughout the 
protocol
The following sections were moved from the main 
body of the protocol or included in a cohort-
specific appendix:
Time and Events Schedules
Pharmacokinetic (PK), Immunogenicity, and 
Biomarker Samples Table
Revision to layout of the protocol 
text to describe each treatment 
cohort of the overall study in a 
cohort-specific appendix. 

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Brief Rationale
Section 2.1. Objectives and Endpoints
Section 2.2. Hypotheses
Section 3.1.1 Phase 1b for Erdafitinib + Cetrelimab 
Cohort/ Phase 1b for Erdafitinib + Cetrelimab + 
Platinum (cisplatin or carboplatin) Chemotherapy 
Cohort
Section 3.1.2 Phase 2 Erdafitinib +/- Cetrelimab 
Cohort
Section 3.3 Dose-Limiting Toxicity Evaluation and 
Determination of RP2D
Section 3.3.1. Definition of Dose-Limiting 
Toxicity for Phase 1b (Dose Escalation)
Section 3.3.2. Determination of the Phase 1b 
RP2D Regimen and Alternative Dosing Schedules
Section 4. Subject Population
Section 4.1. Inclusion Criteria
Section 4.2. Exclusion Criteria
Section 5. Treatment Allocation and Blinding
Section 6. Dosage and Administration
Section 6.1. Dose Combination for Erdafitinib + 
Cetrelimab Cohort/ Dose Combination for 
Erdafitinib + Cetrelimab + Platinum 
Chemotherapy Cohort/ Dose Combination for 
Erdafitinib +/- Cetrelimab Cohort
Section 6.4. Administration of Platinum 
Chemotherapy (Cisplatin or Carboplatin)
6.4.1. Cisplatin
6.4.2. Carboplatin
6.4.3 Antiemetic Therapy and Supportive Care 
Guidelines for Platinum Chemotherapy
6.4.4. Dose Modification, Dose Delays, and 
Retreatment Criteria for Platinum Chemotherapy
6.4.5.Guidance for Specific Platinum 
Chemotherapy Toxicities
6.4.6. Platinum Chemotherapy Associated 
Toxicities Leading to Discontinuation of Study 
Treatment
Time and Events 
Schedules (Appendix 
1, Appendix 2, 
Appendix 3)
A separate Time and Events Schedule has been 
created for each of the 3 cohorts within this study. 
To provide a separate cohort-
specific Time and Events 
Schedule.
Tables for 
Pharmacokinetic, 
Immunogenicity, and 
Biomarker Samples 
(Appendix 1, 
Appendix 2, 
Appendix 3)
The PK, immunogenicity, and biomarker sampling 
text has been removed from the Time and Events 
Schedule. A cohort-specific table containing the 
sampling cycle days and times for PK, cetrelimab 
immunogenicity, and biomarker collection has 
been added to each appendix. 
To provide a separate cohort-
specific table containing the PK, 
immunogenicity, and biomarker 
sampling requirements.
1. Introduction
A description of the new layout of the protocol was 
added. 
To provide the reader with an 
explanation regarding the 
reorganization of protocol text 
based on the main body of the 
protocol and cohort-specific text 
in the respective appendices.

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Brief Rationale
4.1 Inclusion Criteria, 
4.2 Exclusion Criteria
The inclusion and exclusion criteria have been 
updated (where applicable) to include the criteria 
for each of the 3 cohorts of the study. The criteria 
that is applicable to the respective cohort is 
indicated by bold text in Sections 4.1 and 4.2. The 
criteria that is not applicable to the respective 
cohort is indicated by greyed out text in Sections 
4.1 and 4.2.
To provide the reader with an 
explanation as to how the 
inclusion and exclusion criteria 
were updated and reorganized to 
accommodate the 3 treatment 
cohorts within the study. 
Synopsis (Overview 
of Study Design, 
Statistical Methods); 
3.1.2. Phase 2; 11.1.2. 
Sample Size - Phase 
2; 11.11. Futility 
Analysis for Phase 2
The description of the futility analysis was deleted.
A higher observed ORR in Phase 
1b implies a low probability of 
stopping due to futility in Phase 2 
and use of Simon’s two-stage 
design not necessary. Therefore, 
conducting Phase 2 is considered 
more efficient without 
implementation of Simon’s two-
stage design which would involve 
a futility analysis. 
11.1.2. Sample Size -
Phase 2
The Simon two-stage design language was deleted. 
11.4. Efficacy 
Analyses (Phase 2 
only)
The last paragraph in this section regarding the 
efficacy analyses of monotherapy and combination 
therapy was deleted. 
11.10. Data Review 
Committee
The following sentences were amended: 
“Additionally, the DRC may review ongoing 
cumulative data from Phase 1b after the RP2D 
has been determined. The committee will review 
results of the planned futility analysis. After the 
review, the DRC will make recommendations 
regarding the continuation of the study.”.
Synopsis (Objectives, 
Endpoints, and 
Hypotheses); 2.1. 
Objectives and 
Endpoints
The primary objective for the Phase 2 part of the 
study was updated as follows: “To evaluate the 
safety and clinical activity of erdafitinib alone and 
in combination with cetrelimab in in first line 
mUC setting cisplatin-ineligible subjects with 
metastatic or locally advanced urothelial cancer 
with select FGFR gene alterations and no prior 
systemic therapy for metastatic disease”.
To better define the Phase 2 
subject population.
Synopsis ( Overview 
of Study Design); 1.7. 
Overall Rationale for 
the Study; 4.1. 
Inclusion criteria 
(Inclusion 6.2)
The definition of cisplatin-ineligibility was 
clarified.
1.3. Erdafitinib; 1.8.1 
Anticipated Benefits 
and Risks for 
Erdafitinib and 
Cetrelimab
Incorporated updated efficacy and safety data from 
Study 42756493BLC2001.
Incorporated updated data 
generated from other studies 
(including 42756493BLC2001) 
that support the objectives, 
endpoints, and subject populations 
in this study.
1.5.2. Summary of 
Clinical Data
Incorporated updated safety and efficacy data from 
the Phase 1b erdafitinib + cetrelimab cohort.
To comply with request from 
Belgian Health Authority.

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Brief Rationale
1.5.2. Summary of 
Clinical Data; 1.8.1 
Anticipated Benefits 
and Risks of 
Erdafitinib and 
Cetrelimab; 3.1.1. 
Phase 1b (Figure 1); 
3.1.1. Phase 1b 
Erdafitinib + 
Cetrelimab cohort 
(Appendix 1)
Text added to confirm the dose of the RP2D as 
endorsed by the SET. 
Confirms designation of the RP2D 
for the Phase 1b erdafitinib + 
cetrelimab cohort.
3.4. Study Evaluation 
Team; 16.1. Study-
Specific Design 
Considerations; 3.3.2. 
Determination of the 
Phase 1b RP2D 
Regimen and 
Alternative Dosing 
Schedules (Appendix 
1); 6.1. Dose 
Combination for 
Erdafitinib + 
Cetrelimab Cohort 
(Appendix 1)
Text amended to describe the role of the SET and 
the DRC and the timing of the data review/analysis 
by the SET and the DRC.
The DRC assumes responsibility 
from the SET regarding the 
review of cumulative data once 
the RP2D of erdafitinib and 
cetrelimab has been determined.
1.5.2. Summary of 
Clinical Data; 3.1.1. 
Phase 1b (Figure 1); 
3.1.2. Phase 2 (Figure 
3); 6.2.1. Dose Up-
titration Guidelines; 
3.1.2. Phase 2:
Erdafitinib +/-
Cetrelimab Cohort
(Appendix 3)
Reported the outcome of the DRC decision to 
change the erdafitinib titration guidelines for 
Phase 1b DL2B and Phase 2 Arm B. 
The DRC recommended to 
remove the requirement for up-
titration from the erdafitinib + 
cetrelimab combinations in order 
to mitigate the incidence of dose 
interruptions and reductions for 
erdafitinib.
3.1. Overview of 
Study Design
Table entitled “Molecular Eligibility Based Upon 
the Following FGFR Alterations” was added. 
To provide clarity regarding 
molecular eligibility for the Phase 
1b and Phase 2 parts of the study.
Synopsis (Subject 
Population); 3.1.1. 
Phase 1b for 
Erdafitinib + 
Cetrelimab + 
Platinum (cisplatin or 
carboplatin) 
Chemotherapy 
Cohorts (Appendix 
2); 11.1.1. Sample 
Size - Phase 1b
Text regarding molecular eligibility was updated as 
follows:
Phase 1b erdafitinib + cetrelimab cohort 
and the Phase 2 erdafitinib +/- cetrelimab 
cohort: select FGFR gene alterations as 
described in Table 4
Phase 1b erdafitinib + cetrelimab + 
platinum chemotherapy cohort: may be 
FGFR wild-type or express select FGFR 
gene alterations as described in Table 4 in 
tumor or blood. Wild-type is defined as 
subjects without FGFR gene alteration 
and subjects with FGFR gene alterations 
other than the select FGFR alterations 
described in Table 4Table 4.
Time and Events 
Schedules (Appendix 
The following statement was added:
To allow remote consent for 
molecular eligibility screening.

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Brief Rationale
1, Appendix 2, 
Appendix 3); 9.1.2. 
Screening Phase
“Consent for molecular screening (but not full-
study screening) may be performed remotely 
including consent by telephone or video 
consultation unless not permitted according to 
local guidance”.
6. Dosage and 
Administration 
(Appendix 1, 
Appendix 3)
The sequence of study drug administration was 
amended to: “On days that both drugs will be 
administered, the sequence of administration will 
be oral erdafitinib followed by the infusion of 
cetrelimab IV”.
To define the sequence of 
administration of study drug(s) 
and to eliminate the time period 
between the administration of 
study drugs.
6.1. Dose 
Combination for 
Erdafitinib + 
Cetrelimab Cohort 
(Appendix 1)
Footnote “c” was amended to remove the time 
requirements between dosing of erdafitinib and 
cetrelimab. 
6.3. Administration of 
Cetrelimab
The following modification was added to the 
administration instructions of cetrelimab: “On days 
on in which both erdafitinib and cetrelimab will be 
administered, oral erdafitinib should be given 
within 1 hour (±15 minutes) before the start of 
cetrelimab IV infusion. On days in which 
erdafitinib + cetrelimab + platinum (cisplatin or 
carboplatin) chemotherapy will be 
administered, oral erdafitinib should be given 4 
hours (±15 minutes) prior to cetrelimab, followed 
by the start of platinum (cisplatin or 
carboplatin) chemotherapy IV infusion., and 
cetrelimab is administered after chemotherapy”.
3.1. Overview of 
Study Design; Time 
and Events Schedules 
(Appendix 1, 
Appendix 3)
The following text was amended: “For subjects 
enrolling in the Phase 1b Alternative Cohort DL2B
and Phase 2 Arm A cohorts, at selected sites,
paired biopsies will be required (where local
regulations permit and if the tumor is 
accessible) at Screening and C2D1 prior to 
erdafitinib administration (biopsy cohort). High-
risk areas of metastases such as brain, pancreas, 
and lung should not be considered as an 
accessible site for biopsy. Biopsies will be 
collected to aim to have a minimum of 15 
evaluable biopsy pairs (total from Phase 1b 
Alternative Dosing DL2B and Phase 2 Arm A 
cohorts). Exceptions may apply upon discussion 
between the investigator and medical monitor.
For patients outside of the biopsy cohort, biopsies 
may be performed where clinically feasible.”.
To provide guidance to the sites 
regarding high-risk areas for 
biopsies.
9.5. Predictive and 
Exploratory 
Biomarkers
Text added to confirm that the sponsor cannot 
authorize performance of high-risk fresh biopsies 
to obtain tissue for retrospective central 
confirmation of FGFR status. 
9.6.11. 
Documentation of 
Hearing Loss; Time 
and Events Schedule 
(Appendix 3)
Text added to describe requirement for the 
documentation of hearing loss for subjects enrolled 
in the Phase 2 erdafitinib +/- cetrelimab cohort.
To describe the audiometry 
requirements for the sub 
population of the Phase 2 cohort. 

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Section Number
and Name
Description of Change
Brief Rationale
5. Treatment 
Allocation and 
Blinding
Section modified to be cohort-specific. 
To provide cohort-specific 
instructions to sites regarding 
treatment allocation and blinding.
Synopsis 
(Evaluations)
A reference to Attachment 9 was added. 
Additional guidance provided to 
site with regard to assessing 
disease progression and the 
utilization of RECIST guidelines.
9.2.2. Treatment After 
Initial Disease 
Progression
The following paragraph was amended: “If the site 
study team makes an initial assessment of 
disease progression, and if the subject is 
clinically stable, treatment with erdafitinib may 
be continued. In the case of imaging-based 
progression (RECIST -defined disease 
progression) subjects may continue to receive 
erdafitinib and cetrelimab study treatment(s) if the 
investigator and sponsor’s clinical team agree and 
if the subject is clinically stable as defined by the 
following criteria”.
9.2.2. Treatment After 
Initial Disease 
Progression
The following statement was modified: “If a 
subject is approved to continue treatment beyond 
initial RECIST defined disease progression, repeat
tumor imaging must be performed at least 
4 weeks but no later than 6 weeks after the first 
tumor imaging indicating PD. repeat imaging 
must be performed within 4 weeks of the initial 
scan showing progression. If repeat imaging 
meets the threshold for PD (≥20% increase in 
tumor burden [minimum 5mm] compared to 
extent of disease at the time of the first 
progression or unequivocal new lesion(s) 
evidence of a new lesion, the subject will be 
discontinued from study treatment therapy. If 
the repeat scan shows further progression of 
disease of >10% increase in tumor burden 
compared to the initial scan showing progression 
OR the patient has any new symptoms/worsening 
clinical status both study drugs must be 
permanently discontinued”.
Attachment 9
Added the RECIST guidelines (version 1.1).
17.9.2. Study 
Termination
The following statement was added: “The sponsor 
will ensure that subjects benefiting from study 
treatment(s) can continue to receive 
treatment(s) after the study has been 
terminated”.
To ensure treatment continuity for 
any subject receiving benefit from 
the study treatment. 
Time and Events 
Schedules (Appendix 
1, Appendix 2, 
Appendix 3)
Footnote/note added:
“CrCl is to be performed only at Screening and 
is calculated by the Cockcroft-Gault formula 
(Attachment 8)”.
To provide guidance to the site 
regarding the required method to 
calculate the estimated creatinine 
clearance.
Synopsis (Overview 
of Study Design)
The method for assessing renal function was 
changed. Utilizing the glomerular filtration rate 
was replaced by calculating creatinine clearance 
via the Cockcroft-Gault equation (Attachment 8).
Attachment 8 
Added the Cockcroft-Gault Formula. 
Time and Events 
Schedules 
(Appendix 1, 
Footnote added: “Guidance for study conduct for 
ongoing subjects in the event of a national 
disaster is provided in Attachment 10”.
Direction provided to site to 
manage study subjects during a 
national disaster.

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Section Number
and Name
Description of Change
Brief Rationale
Appendix 2, 
Appendix 3)
7. Treatment 
Compliance
Text added for guidance on study conduct for 
enrolled subjects during a national disaster.
Attachment 10
Added standard guidance regarding protocol 
requirements during the time of a national disaster.
6.2.1. Dose Up-
titration Guidelines;
6.2.3.1. Grading of
Hyperphosphatemia 
and Nail Disorders; 
6.2.3.2. Guidelines 
for the Management 
of Elevated Phosphate 
Levels
Serum phosphate values in the text and associated 
tables were updated. 
To align with erdafitinib program 
standards.
6.2.3.3. Guidelines 
for Management of 
Dry Mouth and 
Stomatitis 
Tables for Guidelines for the Management of Dry 
Mouth (Xerostomia) and General Prophylaxis and 
Guidelines for the Management of Oral Mucositis 
were updated.
6.2.3.5. Guidelines 
for the Management 
of Nail 
Toxicity(Onycholysis, 
Onychodystrophy, 
and Paronychia) 
Table for “General Prophylaxis & Guidelines for 
the Management of Nail 
Discoloration/Loss/Ridging 
(Onycholysis/Onychodystrophy)” was updated.
8.3. Precautions for 
Concomitant 
Medications, Food, 
and Surgical 
Intervention
Text and table regarding the use of moderate 
inhibitors of CYP2C9 and strong CYP3A4 
inducers were amended. 
9.6.7. Ophthalmic 
Examination
The following sentence was amended: “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”.
Attachment 5
Amsler grid replaced with new version.
Throughout the 
protocol
NCI-CTCAE version 4.03 updated to version 5.0.
12.1.3. Severity 
Criteria; 12.3.3. 
Disease-related 
Events or Outcomes 
Not Qualifying as 
Adverse Events or 
Serious Adverse 
Events; Attachment 7: 
Anticipated Events
Updated protocol template language replaced by 
existing protocol text. 
To align with updated company 
protocol template language.
Throughout the 
protocol
Nomenclature revised to show:
“cohort”: Phase 1b erdafitinib + cetrelimab 
o “regimen”: Standard and Alternative

“dose level”: DL1, DL2, DL2A, etc.
“cohort”: Phase 1b erdafitinib + cetrelimab + 
platinum chemotherapy 
Clarification of existing text.

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Section Number
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Brief Rationale
o “regimen”: cisplatin or carboplatin

“dose level”: DL2C, DL2C1, etc.
“cohort”: Phase 2 erdafitinib +/- cetrelimab 

“dose level”: Arm A or Arm B.
Throughout the 
protocol
“Time and Events Schedule” is replaced with 
“cohort-specific Time and Events Schedule”.
Throughout the 
protocol
Cycle duration was defined as:
o
4 weeks (28 days) for the Phase 1b 
erdafitinib + cetrelimab cohort and the 
Phase 2 erdafitinib +/- cetrelimab 
cohort
o
3 weeks (21 days) for the Phase 1b 
erdafitinib + cetrelimab + platinum 
chemotherapy cohort.
Throughout the 
protocol
The phrase “selected FGFR alterations” was 
updated to “select FGFR alterations”.
Time and Events 
Schedules (Appendix 
1, Appendix 2, 
Appendix 3)
The following note was amended as follows :

“Subjects enrolling based on local historical 
testing must submit archival tumor tissue and a 
blood sample for retrospective confirmation of 
FGFR status as soon as possible after 
enrollment”. 
3.3.2. Determination 
of the Phase 1b RP2D 
Regimen and 
Alternative Dosing 
Schedules 
(Appendix 1)
First sentence in paragraph updated to “The RP2D 
of the erdafitinib/cetrelimab combination will be 
determined after review of all available PK, PD, 
safety, and efficacy data from at least 6 subjects 
treated at the RP2D and the recommended dose by 
mTPI-2 design. Only 1 RP2D will be tested in 
Phase 2”.
Synopsis 
(Hypotheses)
The hypothesis for the Phase 2 (Dose Expansion)
part of the study was amended as follows: 
“Erdafitinib alone and in combination with 
cetrelimab is are safe and have has anti-tumor 
activity in cisplatin-ineligible subjects with 
metastatic or locally advanced urothelial cancer 
with selected FGFR gene alterations and no prior 
systemic therapy for metastatic disease”.
1.3 Erdafitinib
The footnote for table entitled “Overall Summary 
of Treatment Emergent Adverse Events (TEAEs); 
Treated Subjects (Study 42756493-BLC2001)” 
was updated to include: “(Study 42756493-
BLC2001 CSR)”.

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Brief Rationale
1.5.2. Summary of 
Clinical Data
The following sentences were amended: “Clinical 
experience with cetrelimab in humans to date is 
based on preliminary data from the ongoing first-
in-human (FIH) monotherapy study (Study 
63723283LUC1001), a multicenter Phase 1/2 
study in subjects with advanced solid tumor 
malignancies. Part 1 The Phase 1b part of the 
study, initiated on 21 November 2016, consists of 
dose escalation cohorts and PK/pharmacodynamic 
(PD) cohorts. The highest doses administered to 
date are 800 mg once every 2 weeks(Q2W) and 
480 mg once every 4 weeks (Q4W); no maximum 
tolerated dose has been identified”.
1.5.2. Summary of 
Clinical Data
The following sentence was amended:
“The purpose of dose expansion in Part 2 the 
Phase 2 part of the study is to further characterize 
the safety and to assess the anti-tumor activity”.
1.7. Overall Rationale 
for the Study
The following sentence was deleted from this 
paragraph to ensure alignment with the title of this 
subsection (which pertains to first line subjects): 
“More recently, and beyond chemotherapy, several 
drugs including PD(L) 1 antibodies and erdafitinib 
have been approved in 2L mUC”.
1.8.1. Anticipated 
Benefits and Risks for 
Erdafitinib and 
Cetrelimab
The following sentence was amended:
“Based on currently available clinical data from 
erdafitinib and cetrelimab as monotherapies as 
well as preliminary data from this study Section 
1.5.2, the safety profiles for erdafitinib and 
cetrelimab are anticipated to be remain
manageable”.
1.8.1. Anticipated 
Benefits and Risks for 
Erdafitinib and 
Cetrelimab
Text within the table entitled “ Potential Risks and 
Mitigation Strategies Associated With Erdafitinib 
and Cetrelimab” was deleted to make table more 
concise. 
3.1. Overview of 
Study Design
The following modifications were made: “Subjects 
enrolled in the Phase 1b erdafitinib + cetrelimab 
cohort Part 1 may have received any number of 
lines of prior therapy, subjects enrolled in Phase 
1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort will have had no prior 
systemic therapy for metastatic disease,
and subjects enrolled in Part 2 Phase 2 will have 
had no prior systemic therapy for metastatic 
disease and will be cis-ineligible (see the Inclusion 
Criteria 6.1 in Section 4.1)”.
3.1. Overview of 
Study Design
The following sentence was amended: “All 
subjects will undergo be assessed for molecular  
eligibility testing during Screening to assess for 
select FGFR alterations (as defined in Table 4) 
only and those with tumors positive for the 
selected FGFR point mutations and translocations 
will be enrolled”.

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Brief Rationale
3.1.2. Phase 2
Figure 3: Overview of the Phase 2: Erdafitinib +/-
Cetrelimab Cohort was amended to change “PD-1” 
to “CET”.
3.2. Study Design and 
Starting Dose 
Rationale
The following paragraph was updated: “The 
recommended monotherapy dose for cetrelimab is 
based on clinical activity in the Phase 1 Study 
63723283LUC1001. One of Tthe identified RP2D 
regimens of cetrelimab is a dose of 240 mg Q2W 
administered intravenously. The cetrelimab 
monotherapy RP2D regimen selection was based 
on an acceptable safety profile, similarity to other 
anti-PD-1 monoclonal antibodies, and preliminary 
evidence that target concentrations are achieved. 
This regimen is being tested in the cohort 
combining erdafitinib and cetrelimab (Dose 
levels DL1, DL2, DL2A in Phase 1b and Arm B 
in Phase 2)”.
3.2. Study Design and 
Starting Dose 
Rationale
The subject population was clarified as locally 
advanced or metastatic urothelial carcinoma.
3.4. Study Evaluation 
Team
The composition of the SET is clarified as: “The 
SET will be chaired by the sponsor’s Molecule 
Responsible Physician and membership will 
include the sponsor Study Responsible Physician, a 
sponsor clinical scientist, a subset of the study 
principal investigators, safety physician (sponsor’s 
Safety Management Team chair), statistician, and 
clinical pharmacologist, along with additional 
sponsor staff, as appropriate”.
6.2.2. Dose 
Modification, Dose 
Delays, and 
Retreatment Criteria 
for Erdafitinib
The following sentence was deleted: Dose cohort 
escalation / de escalation rules for Phase 1b are 
described in Section 3.1.1 of the protocol.
6.3.1. Retreatment 
Criteria for 
Cetrelimab
The following modification was made to the text 
regarding the retreatment criteria for cetrelimab: 
“Chemistry and hematology should be assessed 
according to the Time and Events Schedule and
laboratory results and general physical status 
must be reviewed prior to administration of 
cetrelimab”.
6.3.2. Dose Delay for 
Cetrelimab
The following sentence was amended: “If 
cetrelimab administration is delayed beyond the 
allowed visit window (Time and Events Schedule, 
Table 1), then the dose will be considered a missed 
dose”.
6.3.3. Cetrelimab 
Associated Toxicities 
Leading to 
Discontinuation of 
Study Treatment
The term “study treatment” was replaced with 
“cetrelimab”.

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Section Number
and Name
Description of Change
Brief Rationale
6.3.4.12. Monitoring 
During and After 
Study Drug
Administration
The following sentence was modified: “Subjects 
should be carefully observed during study agent
cetrelimab infusions”.
8. Concomitant 
Therapy
Text was amended as follows: “In Phase 1b, aAll 
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 eCRF. For Phase 2, all 
therapies should be documented from the start of 
the study through Cycle 3; after the end of Cycle 3 
only therapies used to treat an AE or SAE should 
be recorded”.
9.1.1. Overview
The following sentence was modified: “The study 
is divided into Screening, Treatment, and Follow-
up Phases. The Time and Events Schedule (Table 1 
and Table 2) for each treatment cohort
summarizes the planned frequency and timing of 
all assessments applicable to this study”.
9.1.2. Screening 
Phase
Clarification made regarding:
molecular eligibility for FGFR status will 
be determined for all subjects
instructions regarding submission of 
biological samples added
requirements of a local laboratory regarding 
molecular eligibility assessment. 
9.3. PK and 
Immunogenicity
The following statement was amended: 
“Pharmacokinetic assessments will be performed 
for both erdafitinib, and cetrelimab, and platinum
(cisplatin or carboplatin) chemotherapy cohort. 
Immunogenicity assessment will be performed 
for cetrelimab”.
9.6.2. Clinical 
Laboratory Tests
The clinical laboratory tests were reorganized into 
categories and footnotes were removed as the 
schedule of laboratory requirements is described in 
the cohort-specific Time of Events Schedules. 
11.3. Analysis 
Population
Text added to describe the Phase 1b and Phase 2 
parts of the study as dose escalation and dose 
expansion, respectively.
11.4. Efficacy 
Analyses (Phase 2 
only)
The following text was amended: “Primary 
endpoint: ORR will be calculated estimated with a 
90 95% confidence interval”.
Attachment 1
The column title was updated as follows: “Number 
of Subjects Treated (at a Dose)”.
1.8.1. Anticipated 
Benefits and Risks for 
Erdafitinib and 
Cetrelimab
Section title added to: “Anticipated Benefits and 
Risks for Erdafitinib and Cetrelimab”.
Updated title of section for clarity.
3.2. Study Design and 
Starting Dose 
Rationale
Subsection title amended to: “Rationale for PK
and PD Assessment”.

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Section Number
and Name
Description of Change
Brief Rationale
3.3.2. Determination 
of the Phase 1b RP2D 
Regimen and 
Alternative Dosing 
Schedules
Section title amended to: “Determination of the 
Phase 1b RP2D Regimen and Alternative Dosing 
Schedules”.
6.2. Administration of 
Erdafitinib
Section title updated to: “Administration of 
Erdafitinib”.
6.3.1. Retreatment 
Criteria for 
Cetrelimab
The section title updated to: “Retreatment Criteria 
for Cetrelimab”.
6.3.2. Dose Delay for 
Cetrelimab
The section title updated to: “Dose Delay for 
Cetrelimab”.
6.3.3. Cetrelimab 
Associated Toxicities 
Leading to 
Discontinuation of 
Study Treatment
The section title updated to: “Cetrelimab 
Associated Toxicities Leading to Discontinuation 
of Study Treatment”. 
Throughout the 
protocol
The term “patient” was changed to “subject”.
Minor errors were noted.
1.2. FGFR Signaling; 
1.3. Erdafitinib
The term “translocation” was changed to “fusion”.
4.2 Exclusion Criteria 
(Criterion 3 of 
Appendix 1, 
Appendix 2, 
Appendix 3)
“4.1” was updated to “3.1”.
Amendment 2 (30 May 2019)
The overall reason for the amendment: To amend the Part 2 study population to evaluate efficacy and safety of 
erdafitinib alone or in combination with cetrelimab in the first line cisplatin-ineligible metastatic urothelial 
carcinoma (mUC) setting. In addition, the amendment includes the lyophilized formulation for JNJ-63723283 
(cetrelimab), addresses requests from health authorities, and addresses the feedback from the investigators on the 
eligibility criteria.
Where an actual text change is shown, this is indicated by bold text.
Applicable Section(s)
Description of Change(s)
Rationale: To amend Part 2 to evaluate efficacy and safety of single-agent erdafitinib alone or in combination with 
cetrelimab in the first line cisplatin-ineligible mUC setting.
Synopsis (Objectives, 
Hypotheses; Overview of 
Study Design; Subject 
Population)
2.1 Objectives and 
Endpoints; 2.2 
Hypothesis (Phase 2);
3.1 Overview of Study 
Design; 3.1.2 Phase 2 
The Part 2 study population is being amended from previously treated to no prior 
systemic therapy for metastatic disease and cisplatin-ineligible. Figure 2 for the 
Phase 2 design has been updated.

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Applicable Section(s)
Description of Change(s)
(Figure 2); 4.1 Inclusion 
Criteria (Criteria 6)
3.2 Study Design and 
Starting Dose Rationale 
(Rationale for the Study 
Population)
Synopsis (Statistical 
Methods); 3.1.1 Phase 1b
3.1.2 Phase 2;
11.1.2 Sample Size-
Phase 2;
11.11 Futility Analysis 
for Phase 2
Synopsis (Objectives, 
Endpoints, and 
Hypotheses); 2.1 
Objectives and 
Endpoints; 9.2.1 Efficacy 
Endpoints
3.3.2 Determination of 
RP2D Regimen and 
Alternative Dosing 
Schedules
Synopsis (Overview of 
Study Design); 3.1 
Overview of Study 
Design; 3.1.2 Phase 2; 5 
Treatment Allocation
5 Treatment Allocation 
and Blinding
The rationale for the subject population has been updated.
Revised statistical assumptions on sample size and futility analysis based on study 
design revisions. The upper limit number of expected subjects in the Phase 1b study 
has been increased from 25 to 30.
Clarified that the ORR will be assessed by investigator assessment.
Text was added to permit exploration of alternative cohort DL2B to further 
characterize the safety of the combination if a standard dosing schedule is identified 
as the RP2D.
Stratification by ECOG PS (0-1 vs 2) has been added.
The stratification text for PD-1 expression was removed due to the updated study 
design. 
Rationale: Incorporate health authority feedback for the country specific UK amendment:

To provide the definition of women of childbearing potential in the inclusion criteria to ensure appropriate 
management of contraception requirements and pregnancy testing.

To make the protocol consistent with the cetrelimab investigator’s brochure information on the use of 
immunosuppressive agents at study entry and during the study.

To clarify exclusion for those with intolerance to protein-based therapies.

To include the final pregnancy test and other critical safety assessments 12 weeks after the last dose of study 
treatment. 
4.1 Inclusion Criteria
Criterion 9
4.2 Exclusion Criteria
Criterion 15
Text is added clarifying the definition of women of childbearing potential.
Allergies, hypersensitivity, or intolerance to protein-based therapies or with a 
history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or 
immune-mediated thrombocytopenia or anemia), or to excipients of erdafitinib 
or cetrelimab (see the Investigator's Brochures for a list of excipients).

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Applicable Section(s)
Description of Change(s)

Originally coagulation tests were included in the protocol for consistency with the FIH study (LUC1001). 
Based on the data generated from this study, there is no risk on clotting factors for the class of PD-1 and PD-
L1. Furthermore, the evaluation of these factors is not in the prescribing information of approved therapies 
(eg, pembrolizumab) 
4.1 Inclusion Criteria 
(Criterion 2)
4.1 Inclusion Criteria
(Criterion 3)
4.1 Inclusion Criteria
(Criterion 4)
4.1 Inclusion Criteria
(Criterion 5)
4.1 Inclusion Criteria
(Criterion 7)
4.1 Inclusion Criteria 
(Criterion 8) 
Histologic demonstration of transitional cell carcinoma of the urothelium. Minor 
components (<50% overall) of vVariant urothelial carcinoma histologies such as 
glandular or squamous differentiation, or evolution to more aggressive phenotypes 
such as sarcomatoid or micropapillary change are acceptable.
To clarify inclusion of metastatic or locally advanced urothelial cancer and to align 
with other ongoing studies in the program:
Stage IV disease (mMetastatic or locally advanced surgically unresectable, cT4b, 
N+, or M+ urotherial cancer.
Removal of text:
Meet appropriate molecular eligibility criteria (as determined by central laboratory
screening).
Criteria modified to enable assessment of response to therapy per RECIST 1.1 
criteria at baseline.
Following text removed/changed:
ECOG performance status PS grade of (see Attachment 3): 0, or 1, or 2.
Following changes made:
Clinical laboratory values Adequate organ function at screening defined as 
follows:
Renal function: Creatinine clearance (CrCl) >50≥40 mL/min/1.73 m2 either directly 
measured via 24-hour urine collection or calculated using the Cockcroft-Gault 
formula
Total bilirubin: ≤1.5 × ULN; subjects with Gilbert syndrome can enroll 
if conjugated bilirubin is within normal limits (≤1.5 x ULN or direct bilirubin ≤ULN 
for subjects with total bilirubin levels >1.5 x ULN
INR or PT
Activated Partial 
Thromboplastin 
Time (aPTT)
≤1.5xULN unless subject is receiving anticoagulant therapy as long 
as PT or PTT is within therapeutic range of intended use of 
anticoagulants
Removal of unnecessarily restrictive electrolyte results as an inclusion criterion.
4.2 Exclusion Criteria 
(Criterion 3)
4.2 Exclusion Criteria 
(Criterion 4)
4.2 Exclusion Criteria 
(Criterion 8)
Included language describing conditions of when neoadjuvant/adjuvant inhibitor 
therapy is allowed.
Removal of text:
Active malignancies (ie, requiring concurrent therapy requiring treatment change in 
the last 24 months) other than urothelial cancer (except skin cancers within the last 
24 months that are considered completely cured).
The exclusion criterion for Corrected QT interval was removed as it is redundant 
with inclusion criterion 8.

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Applicable Section(s)
Description of Change(s)
4.2 Exclusion Criteria 
(Criterion 16)
Exclusion 16 was modified based on health authority recommendation to another 
study in the erdafitinib program (BLC3001) to remove baseline ocular conditions 
from the exclusion criteria. 
4.2 Exclusion Criteria 
(Criterion 17)
4.2 Exclusion Criteria) 
(Criterion 22)
4.1 Inclusion Criterion 9; 
4.2 Exclusion Criteria 15 
and 18
Removal of exclusion criteria referring to CYP3A4 inhibitors.
Removed/added text:
Major surgery within 4 weeks of enrollment, or will not haveinadequate recovered
recovery from the toxicity and/or complications from the intervention prior to 
starting therapy, or has surgery planned during the time the subject is expected to 
participate in the study or within 2 weeks after the last dose of study drug 
administration. (Note: subjects with planned surgical procedures to be conducted 
under local anesthesia may participate.)
See rationale for the UK country specific amendment for details.
Rationale: Updated guideline text on the rules of dose modifications until resolution of an AE, eye toxicities, and 
dry eye.
6.1 Dose Combination 
Cohorts/Arms (note 
added to Table 7)
6.2.2 Dose Modification, 
Dose Delays, and 
Retreatment Criteria for 
Erdafitinib (Table 8)
6.2.3.6 Guidelines for 
Eye Toxicity Associated 
with Vision Changes 
(Table 17)
6.2.3.7 Guidelines for the 
Management of Dry Eye
Text added describing guidance for management of toxicities associated with the 
study drugs and actions to be taken for both study drugs in the event of a ≥Grade 3 
AE thought not attributable to erdafitinib, cetrelimab or the disease under study.
Text added in Table 8 to clarify when and if actions should be taken for Grade 2 
events, and what dose modification rules should be applied for resolution of an AE 
for Grade 2 and Grade 3 AEs.
A footnote referring to Table 9 in the protocol has been added.
The following sentence was added to Grade 1-3 toxicities:
Retinal pigment epithelial detachment, if observed, should be monitored at 
approximately 2 to 3-week intervals until resolution.
The following sentence was added to only Grade 2 toxicities:
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.
Added ocular demulcents and removed hydrating/lubricating eye gels and ointments 
from the guidelines.
Rationale: Updates on background information.
1.1 Urothelial Bladder 
Cancer
1.2 FGFR Signaling
1.3 Erdafitinib
Updated text on the available regimens for urothelial bladder cancer.
Additional information added about deregulation of FGFR signaling and FGFR 
alterations.
Addition of a short description of the JNJ-42756493BLC3001 THOR Study.
IC50 values with respect to erdafitinib inhibition potency has been updated:
< 1 to <1000 130 nM in FGFR pathway-activated cancer cell lines

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Applicable Section(s)
Description of Change(s)
1.3 Erdafitinib; 1.7 
Anticipated Benefits and 
Risk
1.5.2 Summary of 
Clinical Data1.6 Overall 
Rational for the Study 
Design
1.7 Anticipated Benefits 
and Risk
The efficacy and the safety results from the Study BLC2001 CSR were updated.
Updates to clinical data from the newest version of the IB were added.
Text describing the rationale for treatment in 1L mUC has been added.
Text describing the SET decision to endorse dose escalation to DL2 and an update 
on the FIH study 63723283LUC1001 has been added. 
Rationale: Changes to Molecular Screening were implemented. Clarified that subjects may by-pass molecular 
screening on BLC2002 study if they have been previously molecular screened on another Janssen-sponsored 
protocol. Added that patients may meet molecular eligibility based on local next generation sequencing (NGS) 
test results to expedite enrolment. Added blood collection to molecular screening process to assess FGFR 
alteration status in circulating cell-free tumor DNA (ctDNA).
Time and Events Tables; 
9.1.2 Screening Phase
Addition of Molecular Eligibility Criteria to the Time and events tables.
Text has been added in Section 9.1.2 to clarify processes during the Molecular 
Screening eligibility period (including text specific for Central Molecular Screening 
and FGFR analysis of tissue or blood by a local laboratory), and the full-study 
screening period.
Rationale: iRECIST criteria not yet fully validated.
Tables and Events Tables 
and throughout the 
protocol
Reference to iRECIST removed throughout the protocol.
Rationale: To include information of the new lyophilized formulation.
14.1 Physical Description 
of Study Drug(s)
This section was updated to include the description of a new lyophilized formulation 
of cetrelimab that may be used in the study.
Rationale: Errors/prior omissions, editorial issues, or changes for clarity/consistency were noted and corrected.
Section 6.3 
Administration of 
Cetrelimab; Throughout 
the protocol
and Time and Events 
Tables 1 and 2
Time and Events Tables; 
9.6.2 Clinical Laboratory 
tests (footnotes a, b, and 
c have been modified or 
updated)
Time and Events Tables; 
9.6.2 Clinical Laboratory 
Tests
Replacement of JNJ-63723283 with cetrelimab and minor editorial changes.
Corrected the window of erdafitinibadministration with cetrelimab for consistency 
across the document.
Removal of bicarbonate and chloride measurements in the serum chemistry panel as 
unnecessary tests. Measurement of albumin, calcium, potassium and PTH have been 
added.
C-reactive protein CRP was removed because it is a non-specific marker which is 
frequently elevated in UC patients.
Coagulation assessments were removed.
The following text has been added for clarification in the efficacy assessments:

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Applicable Section(s)
Description of Change(s)
Time and Events Tables; 
9.1.2 Screening Phase
9.3 Pharmacokinetics and 
Immunogenicity
3.1.1 Phase 1b
3.1.1 Phase 1b (Figure 1);
6.1 Dose Combination 
Cohorts/Arms
6.2.1 Dose Up-titration 
Guidelines
Table of Events Tables; 
6.3 Administration of 
Cetrelimab
8. Concomitant Therapy
8.2 Prohibited 
Medications (Table 28)
8.3 Precautions for 
Concomitant 
Medications, Food, and 
Surgical Intervention; 
Attachment 4
9.2 Efficacy Evaluations
9.2.2 Treatment After 
initial Disease 
Progression
9.6.6 Echocardiography 
or MUGA Scan
9.6.7 Ophthalmic 
Examination
12.3.1 All Adverse 
Events
Disease assessments done within 35 days prior to C1D1 may be used as the 
Screening disease assessment.
Corrected timing of PK assessments, biomarker and immunology assessments and 
merged these assessments with the Time and Events Tables.
Phase 1b figure replaced with more decipherable figure.
Clarified that 8mg with or without up-titration may be considered as the same dose 
level.
Added mmol/L values in brackets next to their corresponding serum phosphate 
concentrations (represented in mg/mL).
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.
Text was added to describe monitoring of vital signs during the 1st and subsequent 
infusions throughout the study
Text added to clarify that once a subject starts subsequent anticancer therapy, data 
collection of concomitant medications will be limited to ongoing or newly developed 
Grade ≥2 immune-related AEs considered related to erdafitinib.
Medications known to increase serum levels of phosphate were removed from
prohibited medications and added to the section with precautions for concomitantly 
administered medications (Table 29, Section 8.3).
Text in this section was updated to be consistent with CYP guidelines in the IB.
Text explaining/clarifying the process for radiographic scans and CT scans at the 
sites has been added.
Clarification of assessments required following approval to continue treatment 
beyond RECIST progression.
New section added.
Clarification text added to mention when ophthalmic exams will be administered, 
what type will be administered, and by whom.
Clarified that once a subject starts subsequent anticancer therapy, collection of AE 
data will be limited to Grade 2 immune-related AEs and serious adverse events 
from the date the new anticancer therapy is initiated until 100 days after the last dose 
of study treatment. Grade 3 and higher AEs, if considered related to study drug, 
occurring more than 100 days after the last dose of study drug should also be 
reported.

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Amendment 1 (22 January 2018)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.
The overall reason for the amendment: To clarify the dose escalation procedures in the Phase 1b part of the 
study and modify the dose-limiting toxicity criteria.
Applicable Section(s)
Description of Change(s)
Rationale: Additional text regarding the dose escalation procedures and a new Figure 1 have been introduced to 
enhance the clarity of Phase 1b part of the study. However, the planned procedures for this part have not changed.
3.1.1 Phase 1b
Additional text has been added to clarify the dose escalation procedures. This includes 
for the case with 3 subjects treated at a dose level. Table 6 has been replaced with Figure 
1. 
Rationale: Removed a redundant criterion in the dose-limiting toxicity criterion: Since the use of 
immunosuppressing agents in excess of corticosteroids is mainly related to Grade 3 or higher immune toxicity as 
described in the management section of the protocol (Section 6.3.4), this is already included by the general Grade 
3 toxicity rule of the DLT criteria.
3.3.1 Definition of 
dose-Limiting 
Toxicity; Table 7 
Dose-Limiting 
Toxicity Criteria
This criterion is removed: Immune-related toxicity requiring the use of therapies in 
excess of corticosteroids (eg, tumor necrosis factor inhibitors or mycophenolate mofetil)
Rationale: The introductory statement in Section 6.2.2 is expanded for further clarification. Section 6.2.2 is 
intended for toxicity management for erdafitinib. The table is intended as guidance for dose reduction based on 
observed toxicity and not for guiding dose escalation or de-escalation for dose cohorts in the Phase 1b of the 
study.
6.2.2 Dose 
Modification, Dose 
Delays, and 
Retreatment Criteria 
for Erdafitinib
The introduction of this section is expanded:
Treatment with erdafitinib should be discontinued or modified based on toxicity as 
described in Table 8 and the specific guidance below. For eye, skin/nail, dry 
mouth/mucositis, liver, and phosphate toxicities, specific management guidelines 
are provided in Sections 6.2.3.1 through 6.2.3.7. This guidance is only intended for 
toxicity management. Dose cohort escalation/de-escalation rules for Phase 1b are 
described in Section 3.1.1 of the protocol.
Rationale: Clarifications have been made for dose reductions for management of hyperphosphatemia
6.2.3.2 Guidelines for 
the Management of 
Elevated Phosphate 
Levels
7.0-9.0 mg/dL
(2.3-2.9 mmol/L)
A dose reduction will be implemented for persistent 
hyperphosphatemia (defined as serum phosphate ≥7 mg/dL for a 
period of 2 months) or if clinically necessary (eg, in the presence 
of additional adverse events linked to hyperphosphatemia or 
electrolyte disturbances).
>9.0-10 mg/dL
(>2.9-3.2 mmol/L)
A dose reduction will be implemented for persistent 
hyperphosphatemia (defined as serum phosphate ≥9 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).
Rationale: The retreatment criteria for hemoglobin has been revised.
6.3.1 Retreatment 
Criteria, Table 19
Hemoglobin
≥8.0 g/dL with or without transfusion, erythropoietin, or both
Rationale: Laboratory criteria for Inclusion Criterion 8 is clarified with normal limits for conjugated bilirubin.

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Applicable Section(s)
Description of Change(s)
Rationale: An assessment window is added for the disease imaging during the first 6 months. 
Table 1 Time & 
Events Schedule,
Disease assessment
and response 
evaluation
Every 6 weeks for 6 months (±3 days)
Rationale: The Safety Evaluation Team (SET) is now referred to as the Study Evaluation Team (SET) 
throughout the protocol, to be consistent with current Sponsor terminology. 
Synopsis;
3.4 Safety Evaluation 
Team
This is changed to Study Evaluation Team (SET).

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Phase 2 (Dose Expansion):
Erdafitinib +/- cetrelimab cohort: Erdafitinib alone and in combination with cetrelimab is safe and has 
anti-tumor activity in cisplatin-ineligible subjects with metastatic or locally advanced urothelial cancer with 
select FGFR gene alterations and no prior systemic therapy for metastatic disease.
OVERVIEW OF STUDY DESIGN
This is a 2-part, multicenter, open-label, Phase 1b-2 study of erdafitinib in combination with 
cetrelimab +/- platinum (cisplatin or carboplatin) chemotherapy, followed by dose expansion in subjects
with metastatic or locally advanced urothelial cancer with select FGFR gene alterations who are ineligible 
for cisplatin and have not received prior systemic therapy for metastatic disease.
Dose escalation decisions in Phase 1b of the study will be made by the Study Evaluation Team (SET). The 
SET procedures are outlined in the SET charter. At least 3 subjects may be dosed at each dose level that 
will be explored. For all dose levels, a specified dose of oral once daily erdafitinib will be given; up-titration 
rules may not apply in specific dose levels, as decided by the SET, based on the totality of the safety data 
observed. 
Phase 1b (Dose Escalation):
Erdafitinib + cetrelimab cohort: (APPENDIX 1:
PHASE 1B ERDAFITINIB + CETRELIMAB)
Two dosing regimens may be explored: Standard Dose Levels (DL1, DL2 or DL2A) or Alternative Dose 
Levels (DL1B or DL2B).
Standard regimen (DL1, DL2, or DL2A)
Subjects with select FGFR alterations will be assigned to a starting dose level (Dose Level 1[DL1]) 
with oral erdafitinib (6 mg) and cetrelimab (240 mg) administered intravenously every 2 weeks 
(Q2W). Dose Level 2 (DL2) will receive erdafitinib (8 mg up-titrated to 9 mg once daily) and 
cetrelimab (240 mg) administered intravenously every 2 weeks at starting Cycle 1 Day 1 (C1D1). 
Dose Level 2A (DL2A) will receive erdafitinib (8 mg [no up-titration] once daily) and cetrelimab 
240 mg administered intravenously every 2 weeks. At Cycle 5, the dose regimen for cetrelimab 
changes to 480 mg every 4 weeks (Q4W). In the Standard Dose Levels, the DLT period is one 
cycle (4 weeks/ 28 days).
Alternative regimen (DL1B and DL2B)
It is hypothesized that the sequential starting (starting with the FGFR inhibitor erdafitinib for 
1 cycle of 4 weeks [28 days] prior to first administration of anti-PD-1 cetrelimab) might mitigate 
potential toxicities or lead to increased clinical benefit compared with concurrent administration. 
The Alternative Dose Level regime starts with a 4-week run-in of erdafitinib with subsequent 
concurrent dosing of erdafitinib and cetrelimab. Dose Level 1B (DL1B) will receive erdafitinib 
(6 mg) and cetrelimab 240 mg administered intravenously on Day 1 and Day 15 of a 4-week cycle. 
Dose Level 2B (DL2B) will receive erdafitinib (8 mg with up-titration to 9 mg after RP2D) and 
cetrelimab 240 mg administered intravenously on Day 1 and Day 15 of a 4-week cycle. At Cycle 5, 
the dose regimen for cetrelimab for all Alternative Dose Levels changes to 480 mg every 4 weeks. 
The Alternative Dose Levels will have a DLT period of 2 cycles (8 weeks). In these Alternative 
dose levels, the administration of cetrelimab is initiated on Cycle 2 Day 1 (C2D1), while the dose 
and schedule of erdafitinib is unchanged.
On 20 August 2019, the SET met to review data from DL2 (8 mg daily erdafitinib with 
up-titration + 240 mg cetrelimab every 2 weeks) and endorsed a RP2D of 8 mg erdafitinib orally once a 
day with up-titration to 9 mg based on C1D15 phosphate level and the dose of 240 mg cetrelimab IV Q2W.

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On 12 May 2020, the Data Review Committee (DRC) made a recommendation to close Dose level 2 in 
Phase 1b and focus enrollment efforts into the Phase 2 part of the study. Therefore, DL2 will be closed. 
DL2B will remain open and will include up-titration of erdafitinib based on serum phosphate concentration 
from blood sample on Day 15 and the absence of significant erdafitinib-related toxicity on C1D15 as 
determined by the investigator.
Erdafitinib + cetrelimab + platinum chemotherapy cohort: (APPENDIX 2:
PHASE 1B 
ERDAFITINIB+ CETRELIMAB + PLATINUM (CISPLATIN OR CARBOPLATIN) 
CHEMOTHERAPY)
Two new regimens will be explored where erdafitinib and cetrelimab will be combined with either cisplatin 
or carboplatin. In the Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort, the doses of 
erdafitinib (8 mg daily, no up-titration) and cetrelimab (360 mg every 3 weeks [Q3W]) are constant, while 
doses of cisplatin and carboplatin may be adjusted based on dose-limiting toxicity as described in the 
protocol and within the range of acceptable doses in the prescribing information (US prescribing 
information, EU SmPC, or equivalent for the region/country).
Erdafitinib + cetrelimab + cisplatin (erdafitinib + cetrelimab + cis) cohort:
First line subjects with or without select FGFR alterations will receive erdafitinib and cetrelimab 
in combination with cisplatin. The starting dose level of cisplatin will be 50 mg/m2 administered 
intravenously on Day 1 of a 3-week cycle (DL2C). If the mTPI-2 criteria for escalation are met in 
DL2C, the dose of cisplatin will be increased to 60 mg/m2 (DL2C1). The DLT period for dosing 
level DL2C and DL2C1 will be 2 cycles (6 weeks/42 days).
Erdafitinib + cetrelimab + carboplatin (erdafitinib + cetrelimab + carbo) cohort:
First line subjects with or without select FGFR alterations will receive erdafitinib and cetrelimab 
in combination with carboplatin. The starting dose of carboplatin (AUC4 mg/mL/min) 
administered intravenously on Day 1 of a 3 week cycle (DL2D). If the mTPI-2 criteria for 
escalation are met in DL2D, the dose of carboplatin will increase to AUC5 mg/mL/min with a 
maximum dose of 750 mg (DL2D1). The DLT period for dosing level DL2D and DL2D1 will be 
2 cycles (6 weeks/42 days).
Phase 2 (Dose Expansion): (APPENDIX 3:
PHASE 2 ERDAFITINIB +/ -CETRELIMAB )
Two dosing arms may be explored: Arm A and Arm B
Subjects who have not received prior systemic therapy for metastatic disease will be stratified by the Eastern 
Cooperative Oncology Group (ECOG) PS (0-1 versus 2) and assigned randomly (1:1 ratio) to either the 
erdafitinib monotherapy treatment at the starting oral dose of 8 mg (Arm A), or the combination treatment 
of erdafitinib and cetrelimab (Arm B). To further characterize safety and clinical activity of the erdafitinib 
and cetrelimab (Arm B) combination, the dose of erdafitinib and cetrelimab will be administered at 8 mg 
(no up-titration) and 240 mg Q2W, respectively for Cycles 1 through 4. At Cycle 5, the dosing regimen of 
cetrelimab is changed from 240 mg Q2W to 480 mg Q4W. Subjects in the Phase 2 dose expansion cohort 
of the study are cisplatin-ineligible. Cisplatin-ineligible subjects are defined as meeting at least one of the 
following criteria:

Impaired renal function defined as calculated by Cockcroft-Gault (See Attachment 8) (Galsky 
2011).

Grade 2 or higher peripheral neuropathy per National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE version 5.0.)

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
Grade 2 or higher hearing loss per NCI-CTCAE version 5.0.

ECOG Performance Status 2.
On 12 May 2020, the DRC recommended to remove the requirement for up-titration of erdafitinib (to 9 mg 
daily [QD] dose) from Arm B of Phase 2 erdafitinib + cetrelimab combination based upon emerging safety 
data.
End of Study Data Collection Timepoint for all ongoing subjects in Phase 1b and Phase 2 (Protocol 
Amendment 5: APPENDIX 4)
Once the end of study data collection timepoint has been achieved, all subjects will transfer to a 
streamlined visit schedule to allow for more flexibility with study assessments and to continue to collect 
required safety information.  
SUBJECT POPULATION
Approximately 160 subjects will be enrolled in this study. Thirty subjects are planned to be enrolled in the 
Phase 1b erdafitinib + cetrelimab cohort. Forty subjects are planned to be enrolled in the Phase 1b erdafitinib 
+ cetrelimab + platinum chemotherapy cohort. Ninety subjects are planned to be enrolled in the Phase 2 
erdafitinib +/- cetrelimab cohort.
Phase 1b (Dose Escalation):
Erdafitinib + cetrelimab cohort: Subjects with metastatic or locally advanced urothelial cancer with select 
FGFR gene alterations as described in Table 4 with any number of prior lines of systemic therapy are 
eligible for enrollment in this part of the study. Subjects must have select FGFR gene alterations in tumor 
or blood. It is expected that 12-30 subjects will be enrolled in the erdafitinib + cetrelimab cohort. Subjects 
must be 18 years or older and have ECOG performance status (PS) Grade of 0-2. 
Erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy cohort:
First line subjects with metastatic or locally advanced urothelial cancer are eligible for enrollment in this 
part of the study. Subjects may be FGFR wild-type or express select FGFR gene alterations as described in 
Table 4 in tumor or blood. Wild-type is defined as subjects without FGFR gene alteration and subjects with 
FGFR gene alterations other than the select FGFR alterations as described in Table 4. Three subjects (either 
wild-type or with select FGFR gene alterations) will be enrolled in the initial erdafitinib + cetrelimab + 
cisplatin dose level (50 mg/m2). If the starting dose is safe, 6 additional subjects will be enrolled into the 
escalated dose of cisplatin (60 mg/m2). Out of 6 subjects, up to 3 subjects can be wild-type and the other 
subjects should be with select FGFR gene alterations. Approximately 10 additional subjects with select 
FGFR gene alterations will be enrolled at the maximum tolerated dose (MTD) for erdafitinib + cetrelimab 
+ cisplatin.
Three subjects (either wild-type or with select FGFR gene alterations) will be enrolled in the initial 
erdafitinib + cetrelimab + carboplatin dose level (AUC4 mg/mL/min). If the starting dose is safe, 6 
additional subjects will be enrolled into the escalated dose of carboplatin (AUC5 mg/mL/min). Out of 6 
subjects, up to 3 subjects can be wild-type and the other subjects should be with select FGFR gene 
alterations. Approximately 10 additional subjects with select FGFR gene alterations will be enrolled at the 
MTD for erdafitinib + cetrelimab + carboplatin. 
In summary, it is expected that approximately 40 subjects will be enrolled in the platinum chemotherapy 
cohort. Subjects must be 18 years or older and have an ECOG PS Grade of 0-1 for cisplatin and 0-2 for 
carboplatin.
Phase 2 (Dose Expansion): Subjects with metastatic or locally advanced urothelial cancer with select
FGFR gene alterations as described in Table 4 who have had no prior systemic therapy for metastatic 
disease and are ineligible for cisplatin are eligible for enrollment in this part of the study. Subjects must 

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have select FGFR gene alterations in tumor or blood. Subjects must be 18 years or older and have ECOG 
PS Grade of 0-2. Approximately 90 subjects in the Phase 2 dose expansion part are expected to be enrolled.
DOSAGE AND ADMINISTRATION
Erdafitinib (6 mg, 8 mg with potential dose adjustments to 9 mg, depending on phosphate levels measured 
on C1D15) will be provided as tablets for oral administration and will be given once daily at approximately 
the same time of the day with or without food. When both drugs are administered on the same day, 
erdafitinib will be administered before cetrelimab (at doses of 240 mg every 2 weeks, 360 mg every 
3 weeks or 480 mg every 4 weeks). Cisplatin will be administered as IV every 3 weeks at 50 mg/m² or 
60 mg/m² and carboplatin at AUC4 mg/mL/min or AUC5 mg/mL/min, every 3 weeks. All subjects will 
continue to receive study treatment until disease progression, unacceptable toxicity, or any other treatment 
discontinuation criteria are met.
Phase 1b (Dose Escalation):
Erdafitinib + cetrelimab cohort: erdafitinib (6 mg, 8 mg with the potential dose adjustments to 9 mg, 
depending on phosphate levels measured on C1D15) will be provided as tablets for oral administration and 
will be given once daily at approximately the same time of the day with or without food. Cetrelimab will 
be administered at doses of 240 mg every 2 weeks (Cycles 1-4) or 480 mg every 4 weeks (starting at 
Cycle 5). When both drugs are administered on the same day, erdafitinib will be administered before 
cetrelimab. 
Erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy cohort: erdafitinib 
(8 mg) will be given once daily at approximately the same time of the day with or without food. Cetrelimab 
and platinum chemotherapy intravenous infusions will be administered on Day 1 of a 3-week cycle. 
Erdafitinib oral dose will be given first, followed by cetrelimab and then platinum chemotherapy. A 
maximum of 4 cycles of platinum chemotherapy will be administered. If platinum chemotherapy is 
discontinued, the subject can continue to receive erdafitinib and cetrelimab.
Phase 2 (Dose Expansion):
Arm A: erdafitinib monotherapy (8 mg up-titrated to 9 mg) will be given once daily at approximately the 
same time of the day with or without food.
Arm B: erdafitinib 8 mg will be given once daily at approximately the same time of the day with or without 
food. Cetrelimab will be administered at doses of 240 mg every 2 weeks (Cycles 1-4) or 480 mg every 
4 weeks (starting at Cycle 5). When both drugs are administered on the same day, erdafitinib will be 
administered before cetrelimab. 
All subjects in Phase 1b and Phase 2 will continue to receive study treatment until disease progression, 
unacceptable toxicity, or any other treatment discontinuation criteria are met.
EVALUATIONS
The safety of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum chemotherapy will be 
assessed based on medical review of safety parameters including but not limited to AEs, vital signs, physical 
examination, ECOG PS, laboratory tests, and electrocardiograms. Corneal or retinal abnormalities for 
subjects receiving erdafitinib will be considered as AEs of special interest. These occurrences should be 
reported as AEs or as serious AEs if the severity is a Grade 3 or higher and require enhanced reporting and 
data collection. Blood samples will be collected to assess the plasma pharmacokinetics (PK) of erdafitinib, 
platinum (cisplatin or carboplatin) chemotherapy and serum PK and immunogenicity of cetrelimab. Blood 
and tumor samples will also be assessed for biomarkers that could 
 
. The evaluation of response will be according to 
RECIST 1.1 (Attachment 9).
CCI

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STATISTICAL METHODS
The number of subjects to be enrolled in Phase 1b will depend on the dose level at which the DLT criteria 
of the combination are met or the RP2D is determined. The total number of subjects to be treated in Phase 1b 
will be approximately 70. Among the 70 subjects, 30 are planned for the Phase 1b erdafitinib + cetrelimab 
cohort.
Approximately 40 subjects will be enrolled in the erdafitinib + cetrelimab + platinum (cisplatin or 
carboplatin) chemotherapy cohort. In Phase 2, approximately 90 subjects will be assigned randomly in a 
1:1 ratio to receive either erdafitinib monotherapy (Arm A) or erdafitinib and cetrelimab combination 
therapy (Arm B). With approximately 45 subjects on Arm A and assuming a true ORR of 45%, the study 
is designed such that the resulting 95% confidence interval for estimating ORR excludes those less or equal 
to 30%. Similarly, assuming a true ORR of 55% in Arm B, approximately 45 subjects results in a 95% 
confidence interval that excludes ORR less or equal to 40%. The objective response rate will be calculated 
with a 95% confidence interval by each arm in the treated population according to the RECIST 1.1 criteria 
(Attachment 9). Safety data will be summarized descriptively. 
The primary efficacy analysis is planned with ~6 months of follow-up from last patient enrolled or sooner 
(if last patient discontinued prior to the 6-month follow-up). This will be the final analysis for the study. 
The primary efficacy analysis will be based on the response assessed by investigators. 

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TIME AND EVENTS SCHEDULE
The Time and Events Schedule for the Phase 1b erdafitinib + cetrelimab cohort can be found in 
the Appendix 1 Table 1.
The Time and Events Schedule for the Phase 1b erdafitinib + cetrelimab + platinum chemotherapy 
cohort can be found in Appendix 2 Table 1.
The Time and Events Schedule for the Phase 2 erdafitinib + cetrelimab +/- cohort of the study can 
be found in Appendix 3 Table 1. 
The Time and Events Schedule for the Phase 1b and Phase 2 cohorts after the end of study data 
collection timepoint has been achieved can be found in APPENDIX 4 Table 1.

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ABBREVIATIONS
ADL
Activities of daily living
AE
adverse event
AJCC
American joint committee on cancer
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the concentration curve
BSA
body surface area
BUN
Blood urea nitrogen
carbo
carboplatin
cet
cetrelimab
chemo
chemotherapy
CI
confidence interval
cis
cisplatin
Cmax
maximum serum concentration
Cmin
minimum serum concentration
CR
complete response
CSR
central serous retinopathy
CT
computed tomography
ctDNA
circulating tumor DNA
CYP
cytochrome P450
DCF
data clarification form
DCR
disease control rate
DDI
drug-drug interaction
DILI
drug induced liver-injuries
DL
dose level
DLT
dose-limiting toxicity
DoR
duration of response
DRC
Data Review Committee
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
eDC
electronic data capture
EMA
European Medicines Agency
EOI
end of infusion
EORTC
European Organization for Research and Treatment of Cancer
erda
erdafitinib 
EU
European union
FDA
Food and Drug Administration
FGFR
fibroblast growth factor receptor
FIH
first-in-human
FLP
final lyophilized product
GCP
Good Clinical Practice
Ha
alternative hypothesis
HBsAg
hepatitis B surface antigen
HCV
Hepatitis C virus
HIV
human immunodeficiency virus
H0
null hypothesis
IB
Investigator’s brochure
IC50
half maximal inhibitory concentration
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
Ig
immunoglobulin
IHC
immunohistochemistry
INR
International normalization ratio

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IPPI
Investigational Product Preparation Instructions
irAE
immune-related adverse event
IRB
Institutional Review Board
IRR
infusion-related reaction
IRRC
Independent Radiologic Review Committee
IV
intravenous
IWRS
interactive web response system
LFT
liver function test
MASCC
Multinational Association for Supportive Care in Cancer
MDSC
myeloid derived suppressor cell
MedDRA
Medical Dictionary for Regulatory Activities
MRI
magnetic resonance imaging
MTD
Maximum tolerated dose
mTPI-2
modified toxicity probability interval
mUC
metastatic urothelial carcinoma
MUGA
multi-gated acquisition scan
MVAC
methotrexate, vinblastine, doxorubicin, cisplatin
NCCN
National Comprehensive Cancer Network
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NGS
next generation sequencing
NSCLC
non-small cell lung cancer
NYHA
New York Heart Association
OCT
optical coherence tomography
ORR
objective response rate
OS
overall survival
PD
pharmacodynamic(s)
PD-1
programmed death receptor 1
PD-L1
programmed death ligand-1
PD-L2
programmed death ligand-2
PFS
progression-free survival
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PQC
Product Quality Complaint
PR
partial response
PRN
when needed
PS
performance status
PT
Prothrombin time
PTH
parathyroid hormone
PTT
Partial thromboplastin time
Q2W
once every 2 weeks
Q4W
once every 4 weeks
QD
daily
QID
four times a day
QTc
Corrected QT interval
QTcF
Corrected QT interval by Fridericia’s formula
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
RP2D
recommended Phase 2 dose
RPED
retinal pigment epithelial detachment
RVO
retinal vein occlusion
SAC
Safety assessment committee
SAE
serious adverse event
SD
stable disease
SET
study evaluation team
SIPPM
Site Investigational Product and Procedures Manual
SUSAR
suspected unexpected serious adverse reaction
TDAR
T-dependent antigen responses
TEAE
treatment-emergent adverse event

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TID
three times a day
Tmax
time to maximum serum concentration
TPN
total parenteral nutrition
Treg
regulatory T cells
TSH
Thyroid stimulating hormone
TTR
time to response
ULN
upper limit of normal
USFDA
United States Food and Drug Administration
WFI
water for injection

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1.
INTRODUCTION
Erdafitinib (JNJ-42756493) is a selective and potent pan-fibroblast growth factor receptor (FGFR) 
kinase inhibitor with demonstrated clinical activity in subjects with metastatic or surgically 
unresectable urothelial cancer and other solid tumors with alterations in the FGFR pathway.
JNJ-63723283 (cetrelimab) is a fully human immunoglobulin (Ig) G4 kappa monoclonal antibody 
that binds to programmed death receptor-1 (PD-1) with high affinity and specificity, blocks 
binding to both PD-1 ligands: programmed death ligand-1 (PD-L1) and programmed death ligand-
2 (PD-L2). Cetrelimab is currently being investigated for the treatment of advanced stage solid 
tumors in the ongoing Phase 1 study Protocol 63723283LUC1001 (EudraCT No. 2016-002017-22; 
NCT02908906).
Platinum-based chemotherapies and PD-1 therapies in eligible patients remain the mainstay of 
systemic therapy in metastatic or locally advanced urothelial cancer but they do not lead to 
adequate long-term outcomes. Various combination treatments including combination of 
platinum-based chemotherapy followed by PD-1 therapy, and 
 
 are showing tolerable safety profiles. 
 
 
 
The main body of this protocol will describe the overall conduct of this study, which will include 
the Phase 1b erdafitinib + cetrelimab, the Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy dose escalation and dose expansion cohorts as well as the Phase 2 
erdafitinib +/- cetrelimab dose expansion treatment arms. The appendices for each cohort will 
provide a granular level of information for each dose level/arm of the study. As the science evolves, 
new combinations of therapies may be added to this study.
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.
Urothelial Bladder Cancer
Bladder cancer is the most common malignancy involving the urinary system. Urothelial (formerly 
called transitional cell) carcinoma is the predominant histologic type in the United States and 
Europe and the 4th most common cancer in males and 11th most common in females
(Cancer Stat Facts 2017); (Cancer Genome 2014). Urothelial cancer can be subdivided into several 
subtypes based on their molecular signature. The Cancer Genome Atlas working group and others 
have reported that urothelial cancer can be classified, via gene expression signature, broadly into 
basal versus luminal subtypes (Cancer Genome 2014); (Choi 2014); (Damrauer 2014). Luminal 1 
tumors, or luminal-papillary tumors, are reported to be enriched for FGFR3 mutations, and 
conversely lacking in immune marker expression and immune cell infiltrate (Choi 2017); 
(Siefker 2018). A study of 412 chemotherapy-naive, invasive, high-grade urothelial tumors 
CCI
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reported that 44% of luminal-papillary tumors have evidence of FGFR alterations and remain 
immunologically “cold” compared with the other subtypes (Robertson 2017); (Siefker 2018).
While therapy of bladder cancer in the early disease stages has significantly improved with the use 
of Transurethral Resection of Bladder Tumor, intravesical chemotherapy, or immunotherapy with 
Bacille Calmette-Guérin, once locally advanced or metastasized the overall survival (OS) 
dramatically decreases. Specifically, in the metastatic setting, OS is often limited with a 5-year 
survival of less than 15% with Stage IV disease (Cancer Stat Facts 2017). The introduction of 
cisplatin-containing chemotherapy regimens, specifically
cisplatin-gemcitabine and the 
methotrexate, vinblastine, doxorubicin and cisplatin regimen (MVAC) significantly improved 
survival and are considered standard of care. Nevertheless, due to the high toxicity of 
cisplatin-containing regimens, nearly half of the patients are ineligible (Bajorin 1999); 
(Galsky 2011); (Yafi 2011) leading to very poor survival rates in this unfit patient population. For 
patients who are not eligible to receive cisplatin-based regimens, carboplatin-based regimens are 
the recommended first line option (EAU Guidelines 2017); (NCCN 2018). Overall response rates 
are 40% to 50% for cisplatin-based regimens and 30% to 40% for carboplatin-based regimens. 
Median survival is 14 to 15 months and 9 to 10 months in these groups, respectively. Once patients 
have failed front-line therapy, the options for further treatment are limited and outcomes dismal. 
Most widely used are single-agent chemotherapy such as docetaxel, paclitaxel or vinflunine, with 
response rate of approximately 10%. Until very recently, there were no approved available 
therapies for second line metastatic urothelial carcinoma (mUC). Five compounds targeting the 
PD-1/PD-L1 pathway have since received approvals in the US for use in patients who have 
received at least 1 prior line of therapy for metastatic urothelial carcinoma; however, with an 
objective response rate (ORR) ranging from approximately 15% to 20% and a median OS of 
approximately 8 to 10 months. Two of these compounds (atezolizumab and pembrolizumab) are 
also approved in the first line setting in patients with UC who are ineligible for cisplatin-based 
regimens. However, the use is restricted due to decreased survival associated with low expression 
of the PD-L1 (Tencentriq® 2016), (Keytruda® 2014). These compounds have only partially 
improved patients’ outcomes and have not eliminated the need for novel treatments
(De Maeseneer 2017). Due to the high unmet medical need, novel therapeutic options are required 
for the treatment of this challenging patient population.
1.2.
FGFR Signaling
The family of FGFRs consists of 4 highly conserved transmembrane receptor tyrosine kinases, 
namely FGFR1 to 4 (Babina 2017). Together, these receptors are able to bind to over 20 different 
fibroblast growth factor ligands (Touat 2015). FGFR signaling has been shown to be enhanced by 
genetic alterations such as gene amplification, mutation, or gene fusions, thereby affecting various 
cellular mechanisms such as angiogenesis, anti-apoptosis, cell migration, and proliferation in 
various cancers. Several lines of evidence point to deregulation of FGFR signaling (eg, via FGFR 
mutation and gene fusion) being involved in bladder cancer pathogenesis (Babina 2017); 
(Dienstmann 2014); (Touat 2015).
In urothelial cancer, amplifications of FGFR 1 to 3 can be found in a subset of patients. More 
importantly, activating mutations of FGFR3 have been shown in 38-66% in noninvasive and 

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15-20% in invasive urothelial cancers (Knowles 2015); (Rodriguez-Vida 2015). Additionally, 
increased expression of FGFR1 and 3, independent of alterations of the FGFR gene have been 
reported in a significant proportion of urothelial cancer patients (Knowles 2015); 
(Rodriguez-Vida 2015) suggesting a therapeutic alternative for this patient population. The panel 
used for subject selection in erdafitinib studies was chosen based on the most frequently observed 
activating FGFR alterations in urothelial cancer (mutations in FGFR3, and FGFR2 and FGFR3 
gene fusions). These include the most commonly observed FGFR3 mutations in bladder cancer: 
S249C, Y373C, R248C, and G370C mutations, which occur in the extracellular or transmembrane 
domains of the receptor leading to ligand-independent dimerization and constitutive activity 
(Dienstmann 2014). Of the selected fusion proteins, FGFR3:TACC3 fusions have the highest 
occurrence in bladder cancer (Rodriguez-Vida 2015). TACC3 fusions, along with the 
FGFR3:BAIAP2L1 fusion and FGFR2 fusion proteins FGFR2:CASP7 and FGFR2:BICC1, confer 
oncogenic potential via substitution of the C-terminal regulatory domain of FGFR with 
protein-protein interaction modules of the fusion partner, leading to ligand-independent 
dimerization and activation of FGFR (Babina 2017); (Katoh 2016); (Wu 2013).
1.3.
Erdafitinib
Erdafitinib is a potent, oral pan-FGFR tyrosine kinase inhibitor with half maximal inhibitory 
concentration (IC50) 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 IC50 values ranging 
from <1 to <130 nM in FGFR pathway-activated cancer cell lines. Erdafitinib has been shown to 
have in vivo anti-tumor activity in various murine xenograft and patient-derived mouse models of 
FGFR-driven cancers including gastric, bladder, and others.
In humans, treatment with erdafitinib exhibited dose-related increase in maximum serum 
concentration (Cmax) and area under the concentration curve (AUC) and time-independent 
pharmacokinetics (PK) within the dose range of 0.5 mg to 12 mg, both after single and multiple 
daily dosing. Median time to maximum serum concentration (Tmax) observed ranged from 2 to 
4 hours (erdafitinib as capsule). Erdafitinib is highly bound to plasma proteins such as α1-acid 
glycoprotein (α1-AGP). In patients, free fractions of erdafitinib in human plasma were small 
(average ~0.36%). In in vitro experiments, erdafitinib was shown to be a P-glycoprotein (P-gp) 
substrate and inhibitor.
Only unchanged erdafitinib was present in plasma with no circulating metabolites. The 
metabolites, mainly N- and O-dealkylated derivatives (M8 and M6, respectively), formed via 
CYP2C9 and CYP3A enzymes, are efficiently eliminated after their formation in the excreta 
(majority excreted in feces). Long terminal phase half-life of erdafitinib (>50 hours) in plasma was 
observed resulting in approximately 3- to 5-fold accumulation of Cmax and AUC following multiple 
daily dosing.
The anti-tumor effect of erdafitinib was initially observed both in subjects with urothelial cancer 
with select FGFR alterations, as well as other solid tumors in the Phase 1 study (Study 
42756493EDI1001). Activity and a dose were confirmed in the global Phase 2 trial (Study 
42756493BLC2001).

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Study 42756493BLC2001 is a global Phase 2 trial in subjects with select FGFR mutations and 
fusions with chemo-refractory and chemo-naïve advanced urothelial cancer who are ineligible for 
cisplatin. As of the clinical cutoff for the primary analysis on 15 March 2018, 210 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 99 subjects in the 8 mg daily regimen (selected dose regimen). Of the 
99 subjects in the primary efficacy population in the 8 mg regimen, 87 (90%) subjects were chemo-
refractory and 12 (10%) subjects were chemo-naïve. Confirmed ORR based on investigator 
assessment (complete response [CR] + partial response [PR]), was 40.4% in the 8 mg once daily 
regimen. For subjects in the 8 mg once daily regimen who were up-titrated to 9 mg, the ORR was 
48.8% (Table 1). The overall summary of treatment-emergent events (TEAEs) from Study 
BLC2001 is presented in Table 2. The most frequently reported AEs in the 8 mg once daily 
regimen, most of which were Grade 1 or 2 in severity, were hyperphosphatemia (77%), stomatitis 
(58%), diarrhea (51%), and dry mouth (46%). Twenty-one subjects (21%) discontinued treatment 
due to AEs. The most common reason for discontinuation was general physical health 
deterioration. The frequency of reported AEs and discontinuations across all dose regimens 
combined was similar to that seen in the 8 mg once daily regimen.
Table 1:
Best Overall Response – Investigator Assessment (8 mg QD) (Study 42756493-BLC2001)
8 mg QD All
8 mg Daily 
Up-titrated to 9-mg Daily
Total number of subjects
99
41
Objective response rate (CR+PR)
40 (40.4%)
20 (48.8%)
95% CI
(30.7%, 50.1%)
(33.5%, 64.1%)
Disease control rate (CR+PR+SD)
79 (79.8%)
31 (75.6%)
95% CI
(71.9%, 87.7%)
(62.5%, 88.8%)
Best overall response
Confirmed complete response (CR)
3 (3.0%)
2 (4.9%)
Confirmed partial response (PR)
37 (37.4%)
18 (43.9%)
Stable disease (SD)
39 (39.4%)
11 (26.8%)
Progressive disease (PD)
18 (18.2%)
10 (24.4%)
Inevaluable (NE)
2 (2.0%)
0
Abbreviations: CR= complete response; NE= not evaluable; PR= partial response; SD= stable disease
95% CI are 95% confidence interval calculated with normal approximation.

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Table 2:
Overall Summary of Treatment Emergent Adverse Events (TEAEs); Treated Subjects (Study 
42756493-BLC2001)
8 mg QD 
6 mg QD 
10 mg 7 on/7 off 
Total 
Total number of subjects
99
78
33
210
Any TEAEs
99 (100.0%)
78 (100.0%)
33 (100.0%)
210 (100.0%)
Drug-related
96 (97.0%)
69 (88.5%)
32 (97.0%)
197 (93.8%)
Grade 3-4 TEAEs
66 (66.7%)
51 (65.4%)
22 (66.7%)
139 (66.2%)
Drug-related
45 (45.5%)
22 (28.2%)
8 (24.2%)
75 (35.7%)
Serious TEAEs
39 (39.4%)
39 (50.0%)
14 (42.4%)
92 (43.8%)
Drug-related
9 (9.1%)
4 (5.1%)
1 (3.0%)
14 (6.7%)
Grade 3-4 serious TEAEs
33 (33.3%)
27 (34.6%)
13 (39.4%)
73 (34.8%)
TEAEs leading to dose 
reduction
55 (55.6%)
32 (41.0%)
13 (39.4%)
100 (47.6%)
Drug-related
55 (55.6%)
26 (33.3%)
12 (36.4%)
93 (44.3%)
TEAEs leading to dose 
interruption
70 (70.7%)
47 (60.3%)
16 (48.5%)
133 (63.3%)
Drug-related
61 (61.6%)
36 (46.2%)
13 (39.4%)
110 (52.4%)
TEAEs leading to treatment 
discontinuation
21 (21.2%)
18 (23.1%)
6 (18.2%)
45 (21.4%)
Drug-related
12 (12.1%)
6 (7.7%)
3 (9.1%)
21 (10.0%)
TEAEs leading to death
7 (7.1%)
15 (19.2%)
4 (12.1%)
26 (12.4%)
Drug-related
0
0
0
0
Subjects with > 1 records are counted only once at corresponding row levels.
Source: Attachment TSFAE01A (Study 42756493-BLC2001 CSR)
As of the clinical cutoff of 09 August 2019 (updated analysis), the median follow-up for 
101 subjects treated in the erdafitinib 8 mg regimen in Study 42756493BLC2001 was ~24 months. 
The confirmed ORR by investigator assessment was 40%. The median duration of response (DoR) 
was 5.98 months. Thirty-one percent of responders had DoR≥1 year. The median PFS was 
5.52 months. The median OS was 11.3 months. The 12 and 24-month survival rates were 49% and 
31%, respectively. Median treatment duration was 5.4 months. The erdafitinib safety profile was 
consistent with the primary analysis. No new TEAEs were seen with longer follow-up. Central 
serious retinopathy (CSR) events occurred in 27% (27/101) of subjects; 85% (23/27) were Grade 1 
or 2. Dosage was reduced in 13 subjects with CSR, interrupted in 8 subjects, and discontinued for 
3 subjects. On the data cutoff date, 63% (17/27) CSR events had resolved; 6 of 10 of the ongoing 
CSR events were Grade 1. There were no treatment-related deaths.
A 
randomized, 
open-label, 
multicenter, 
global 
Phase 
3 
study 
(THOR 
study 
[JNJ-42756493BLC3001]) of erdafitinib versus standard of care is being conducted in subjects 
with advanced urothelial cancer and select FGFR aberrations 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 anti-PD(L)-1 agent (Cohort 2).
For the most comprehensive nonclinical and clinical information regarding erdafitinib, refer to the 
latest version of the Investigator's Brochure (IB) and IB Addenda for erdafitinib.

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1.4.
PD-1/PD-L1 Signaling
PD-1, a member of the B7 family of proteins, is a co-inhibitory immune checkpoint receptor that 
regulates adaptive T cell immunity. PD-1 is required for maintenance of peripheral tolerance 
during normal immune homeostasis, as well as for protection against excessive inflammation 
during acute immune responses. PD-1 is expressed on activated CD4+ and CD8+ T cells and acts 
to limit antigen-specific T cell activity through interaction with its ligands, PD-L1 and PD-L2. 
Cancer cells may often exploit the PD-1/PD-L1 pathway to escape immune surveillance. PD-L1 
expressed on cancer cells initiate an immune-inhibitory signal through the PD-1 receptor on 
regulatory T cells (Tregs), leading to inhibition of T cell activation and proliferation, thereby 
negatively affecting the anti-cancer immune response, an essential mechanism of self-tolerance of 
the human body.
Clinical studies have shown that the PD-1/PD-L1 pathway is an attractive therapeutic target by 
reversing T cell exhaustion and boosting the anti-tumor immune response. In urothelial cancer, 
this approach was extensively explored with a variety of antibodies that blocked PD-1 and/or 
PD-L1, leading to the approval of several antibodies, such as atezolizumab and pembrolizumab, 
showing promising clinical activity (De Maeseneer 2017).
1.5.
Cetrelimab
1.5.1.
Summary of Nonclinical Data
In vitro assays with cetrelimab showed enhanced T cell function and reversed PD-1 mediated 
suppression of T cell receptor signaling by promoting nuclear factor of activated T cells 
(NFAT)-reporter transcriptional activity. These findings with cetrelimab were comparable to the 
observed activities for 2 anti-PD-1 monoclonal antibody analogues for nivolumab and 
pembrolizumab. In vivo, cetrelimab inhibited tumor growth in human PD-1 knock-in mice bearing 
MC38 murine colon carcinoma tumors and showed comparable anti-tumor efficacy to a nivolumab 
analogue.
Toxicology studies in cynomolgus monkeys indicate cetrelimab was well tolerated and the pivotal 
Good Laboratory Practice 5-week study demonstrated T-dependent antigen responses (TDAR). 
No cetrelimab -related effects were noted in the cardiovascular, respiratory, or central nervous 
system during the 5-week study. Primary cetrelimab -related findings noted in 4- and 5-week 
monkey studies at ≥10 mg/kg/wk included slight increases in blood monocyte counts and 
prothrombin times, and minor/transient decreases in absolute counts for blood CD3+T, 
CD3+/CD4+ T-helper, and CD3+/CD8+ T-cytotoxic lymphocytes, increases in the IgM and IgG 
secondary TDAR response to keyhole limpet hemocyanin antigen challenge, and minimally 
reduced thymic cellularity (decreased lymphocytes) that were considered not to be toxicologically 
significant. None of these findings were considered adverse and are anticipated to present low to 
no clinical risk in humans (eg, reduced thymic cellularity that was minimal in nature and was not 
associated with a correlative decrease in thymus weight or in thymus-to-body and thymus-to-brain 
ratios). In the 5-week study, the no-observed-adverse-effect-level was 100 mg/kg/wk (mean Cmax
3,055.75 µg/mL and AUCDay29-36 12,658.15 µg day/mL following the dose on Day 29). 
Additionally, cetrelimab did not induce hemolysis in whole human blood and was compatible with 

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human serum at in vitro concentrations between 0.010 to 10 mg/mL, and the cetrelimab cytokine 
response in vitro in human blood was similar to other immune-modulatory compounds that have 
a low risk of cytokine release syndrome.
1.5.2.
Summary of Clinical Data
Clinical experience with cetrelimab in humans to date is based on preliminary data from the 
ongoing first-in-human (FIH) monotherapy study (Study 63723283LUC1001), a multicenter 
Phase 1/2 study in subjects with advanced solid tumor malignancies. The Phase 1b part of the 
study, 
initiated 
on 
21 November 2016, 
consists 
of 
dose 
escalation 
cohorts 
and 
PK/pharmacodynamic (PD) cohorts. The highest doses administered to date are 800 mg once every 
2 weeks (Q2W) and 480 mg once every 4 weeks (Q4W); Part 1 has established a recommended 
Phase 2 dose (RP2D), which may be administered at either 240 mg (Q2W) or 480 mg (Q4W), 
based on interim safety, PK, and PD data. In the Phase 2 part of the study, initiated on 
03 May 2017, this RP2D is being evaluated in selected solid tumor types including non-small cell 
lung cancer (NSCLC), melanoma, bladder cancer, renal cancer, small cell lung cancer, and 
gastric/esophageal cancer. The purpose of dose expansion in the Phase 2 part of the study is to 
further characterize the safety and to assess the anti-tumor activity.
In September 2017, additional interim safety, PK and PD data to support an alternate regimen 
(480 mg Q4W) with the same total dose as RP2D of 240 mg Q2W but given with a longer dosing 
interval was shown to enable flexibility of drug administration in various clinical settings.
Selection of the RP2D of 240 mg Q2W and 480 mg Q4W was based on the following:

No MTD has been identified with administration of doses up to 460 mg Q2W and 
480 mg Q4W and doses were well tolerated.

Cetrelimab demonstrated comparable preclinical in vivo tumor growth inhibition and 
comparable in vitro activity across various assays as the approved PD-1 inhibitors nivolumab 
and pembrolizumab. Therefore, similar clinical efficacious target concentrations would be 
expected for cetrelimab.

Based on preliminary PK data, the median observed near-steady-state Cmin for cetrelimab at 
240 mg Q2W is 44.8 µg/mL (N=5, trough concentration before the fifth dose). This is 
comparable to the Cmin,ss reported for nivolumab (57 µg/mL [CDER Opdivo 2014, CMPH 
Opdivo 2017])
and pembrolizumab (23 µg/mL[CDER Keytruda® 2014, CMPH 
Pembrolizomab 2017]) at their approved doses (240 mg Q2W for nivolumab and 2 mg/kg or 
200 mg Q3W for pembrolizumab).

The median steady-state Cmin,ss for cetrelimab at 480 mg Q4W is expected to be approximately 
42 µg/mL, based on an observed median Cmin after first dose at 30 µg/mL and predicted 
accumulation ratio of ~1.4 based on preliminary PK modeling. The Cmin,ss from 240 mg Q2W 
and 480 mg Q2W is therefore expected to be comparable, and in range with other anti-PD-1 
agents nivolumab and pembrolizumab at their approved clinical dose.

Administration of cetrelimab resulted in saturation of PD-1 RO on circulating CD3+ T cells 
at all administered doses (80 to 480 mg) and dosing frequencies (Q2W and Q4W).

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In addition, a relatively flat dose-response relationship has been demonstrated for 2 approved 
anti-PD-1 agents (nivolumab or pembrolizumab), suggesting a relatively broad therapeutic 
window (around 1 mg/kg to 10 mg/kg) for this mechanism of action where various doses and 
dosing regimens may lead to comparable clinical benefit/risk profile. The RP2D for cetrelimab, 
therefore, may be administered at either 240 mg Q2W or 480 mg Q4W, ie, same dose level with 
corresponding dosing frequencies that would result in the same total dose as 240 mg delivered 
every 2 weeks, while demonstrating acceptable safety as well as providing sufficient PK/PD 
coverage to ensure RO saturation throughout dosing interval. Investigation of additional dose 
levels and dosing frequencies (aside from 480 mg Q4W) may continue to be explored as 
alternative means to deliver the same RP2D (240 mg Q2W) (Investigator’s Brochure for 
JNJ-63723283 2018).
Overall, the safety profile has been similar to that of other anti-PD1 agents (such as nivolumab and 
pembrolizumab), although a higher percentage of treatment-emergent infusion-related reactions 
(IRR) have been observed to date. The IRRs were reported for 24 (12.5%) treated subjects; 
majority were Grade 2 in severity, transient, and resolved with temporary interruption of the 
infusion and subjects received the full dose. The most frequently reported treatment-emergent 
IRRs were nausea, back pain, and dyspnea (4 subjects each) and pyrexia (3 subjects). Other events 
reported as IRRs in more than 1 subject included chills, erythema, rash, rash generalized, vomiting, 
flushing, and hypertension (based on 03 September 2018 data cut). Most subjects who were 
reported with IRRs received cetrelimab 240 mg Q2W, with the exception of 1 subject each who 
received cetrelimab 460 mg Q2W and 480 mg once every 4 weeks, and 2 subjects who received 
800 mg Q2W.
In total, as of 03 September 2018, 192 subjects received at least 1 dose of cetrelimab, and of these, 
156 subjects were evaluable for response. The ORR (CR+PR) was 15.4%, 2 (1.3%) subjects had 
a complete response and 22 (14.1%) had a partial response as assessed by the investigator.
As of the pharmacokinetic data cutoff date of 17 May 2018, the preliminary pharmacokinetic 
analysis included a total of 100 PK-evaluable subjects. Serum concentration data following the 
first dose of cetrelimab exhibited approximately linear PK. Maximum serum concentration (Cmax), 
minimum serum concentration after the first dose (Cmin1), and area under the curve for 1 dosing 
interval (AUCtau) increased in an approximately dose-propartal manner from 80 to 800 mg. 
Interpatient variability was generally consistent with mAb therapeutics. Based on preliminary 
population PK modeling, the Cmin, steady-state from 240 mg Q2W and 480 mg Q4W is 
comparable, and in range with other anti-PD-1 agents such as nivolumab or pembrolizumab at 
their respective approved clinical dose. In addition, PD-1 receptor occupancy on circulating 
CD3+ T cells was evaluated in 60 subjects and preliminary results indicated that post-dose 
saturation occurred throughout dosing interval at all dose levels (ranging from 80 mg to 800 mg) 
and all dosing frequencies (ranging from Q2W to Q4W).
The RP2D for cetrelimab, therefore, may be administered at either 240 mg Q2W or 480 mg Q4W, 
ie, same dose level with corresponding dosing frequencies that would result in the same total dose 
as 240 mg administered Q2W, while demonstrating acceptable safety as well as providing 

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sufficient PK/PD coverage to ensure RO saturation throughout dosing interval. Investigation of 
additional dose levels and dosing frequencies (aside from 480 mg Q4W) may continue to be 
explored as alternative means to deliver the same RP2D (240 mg Q2W) (Investigator’s Brochure 
for JNJ-63723283 2018).
For the Phase 1b erdafitinib + cetrelimab cohort and Arm B in the Phase 2 part of the study, 
cetrelimab will be dosed at 240 mg Q2W for Cycles 1 through 4 and 480 mg Q4W starting at 
Cycle 5. For the Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort, cetrelimab 
will be dosed at 360 mg Q3W intravenously to align with the dosing frequency of platinum 
chemotherapy. 
 
 
For the most comprehensive nonclinical and clinical information regarding cetrelimab, refer to the 
latest version of the Investigator's Brochure and Addenda for cetrelimab.
Erdafitinib in combination with Cetrelimab – Clinical Data from BLC2002
SET endorsement of RP2D
The SET for this study met in January 2019 to review data from DL1 (6 mg daily 
erdafitinib + 240 mg cetrelimab Q2W). No DLTs were noted, and the SET endorsed the dose 
escalation to the next dose level DL2A. On 17 May 2019, the SET met to review data from DL2A 
(8 mg daily erdafitinib with no up-titration + 240 mg cetrelimab Q2W). No DLTs were noted, and 
the dose level was cleared by the SET. Further, the SET endorsed the dose escalation to the next 
dose level DL2. On 20 August 2019, the SET met to review data from DL2 (8 mg daily erdafitinib 
with up-titration + 240 mg cetrelimab Q2W) and endorsed a RP2D of 8 mg erdafitinib orally once 
a day with up-titration to 9 mg based on C1D15 phosphate level and the dose of 240 mg cetrelimab 
IV Q2W.
Additional interim safety, PK and PD data to support an alternate regimen (480 mg Q4W) with 
the same RP2D of 240 mg Q2W of cetrelimab but given with a longer dosing interval enables 
flexibility of drug administration in various clinical settings. Thus, the dosing of cetrelimab at 
Cycle 5, is increased to 480 mg Q4W.
As of 08 January 2020, 17 subjects were enrolled in the dose escalation (Phase 1b) part of this 
ongoing study. All 17 subjects experienced an AE. Nine subjects (52.9%) experienced Grade ≥3 
related AEs and 2 (11.8%) experienced serious adverse events (SAEs). Four (23.5%) subjects 
experienced AEs leading to discontinuation of study drug.
The most common (≥25%) AEs (any Grade) across all dose levels were stomatitis (70.6%), 
diarrhea (58.8%), dry mouth and hyperphosphatemia (52.9% each), dysgeusia (41.2%), dry skin 
(35.3%), alopecia, asthenia, and pyrexia (29.4% each). Ocular events including CSR are known 
class effects of inhibition of the mitogen-activated protein kinase pathway (Chae 2017; 
Rutkowski 2019). Three of 17 subjects across all doses experienced a CSR event. All events were 
Grade 2 that resolved to Grade 1 at the time of the data cutoff.
CCI

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At the RP2D of 8 mg with an up-titration erdafitinib + cetrelimab (n=10), all subjects reported 
AEs. Six of 10 (60%) subjects experienced related Grade ≥3 AEs. Two of 10 (20%) experienced 
related serious related AEs. The most common AEs observed were similar to those across all doses. 
Two of 10 (20%) of the subjects reported a Grade 2 CSR event that had resolved to Grade 1 at the 
time of the data cutoff.
Forty-one percent of the subjects across all cohorts discontinued erdafitinib + cetrelimab. The 
majority (n=4) were in the initial dose cohort (6 mg erdafitinib + cetrelimab). The reasons for 
discontinuation were AE (n=1; urinary tract infection assessed as not related to study drugs), 
progressive disease (PD) (n=5), and death (n=1; colonic obstruction assessed as not related to study 
drugs). One subject treated at the RP2D discontinued due to PD.
The objective response rate was 50.0% and disease control rate (DCR) was 93.8% in 
response-evaluable subjects across all cohorts (n=16). In subjects treated at the RP2D (erdafitinib 
8 mg with up-titration + cetrelimab 240 mg [n=9]), the objective response rate was 44.4% and 
DCR was 100%.
On 12 May 2020, the DRC discussed the requirement for up-titration from Arm B of Phase 2 
erdafitinib + cetrelimab combination. Erdafitinib exposure data was reviewed and showed that the 
median dose intensity of DL2A (8 mg erdafitinib without up-titration + cetrelimab) was 
6.14 mg/day, which was higher than the dose intensity of DL2 (8 mg erdafitinib with up-titration 
+ cetrelimab, median 5.65 mg/day). It was postulated that subjects who were up-titrated were 
experiencing AEs such as stomatitis, which may have caused lengthy dose interruptions and more 
reductions as compared with non-up-titrated patients. Based on this, the DRC recommended to 
remove the requirement for up-titration from Phase 2 Arm B to further explore if 8 mg erdafitinib 
flat dosing could mitigate the incidence of dose reductions and interruptions due to AEs. The DRC 
also made a recommendation to close Dose level 2 in Phase 1b and focus enrollment efforts into 
the Phase 2 part of the study. Therefore, DL2 will be closed. DL2B will remain open and will 
include up-titration of erdafitinib based on serum phosphate concentration from blood sample on 
Day 15 and the absence of significant erdafitinib-related toxicity on C1D15 as determined by the 
investigator.
On 11 September 2020, the DRC convened for a scheduled review of the first 20 subjects 
randomized in the Phase 2 part of the study. The DRC recommendation was to continue the study 
as planned. Of particular note, the DRC reviewed a case of one subject death in Arm B due to 
pulmonary failure, which was assessed by the sponsor to be related to cetrelimab and not related 
to erdafitinib. The DRC noted that identification and early treatment of immune-related AEs 
(irAEs) are essential in limiting duration and severity. To manage the risk of irAEs, specific risk 
mitigation measures are included in the study protocol. Subjects with active autoimmune disease 
or a history of Grade 3 or higher toxicity effects from previous treatment with immunotherapy, are 
excluded from participating in the study. Management algorithms have been included to provide 
instructions for study drug interruption or dose delay (Section 6.3.2) and permanent 
discontinuation (Section 6.3.3) to minimize the risk of irAEs. Algorithms targeted to specific irAEs 

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such as pulmonary irAEs (Section 6.3.4.7) and gastrointestinal irAEs (Section 6.3.4.1) are also 
included.
1.6.
Platinum Chemotherapy in Metastatic Urothelial Cancer
Platinum-based combination chemotherapy has been the standard of care in the first line treatment 
of metastatic urothelial carcinoma (mUC) (Bukhari 2017) as defined by current American Joint 
Committee on Cancer (AJCC) criteria. A cisplatin-based combination chemotherapy regimen is
the preferred initial therapy for patients with mUC of the bladder and urinary tract who are cisplatin 
candidates. Depending on PD-L1 expression, or ineligibility to cisplatin-based treatment, 
atezolizumab and pembrolizumab are treatment options for some patients with metastatic 
urothelial cancer. Cisplatin-based combination chemotherapy results in superior survival when 
compared with single-agent cisplatin. A small proportion of patients with distant metastases in the 
nodes or lung may be cured by combination chemotherapy. However, cisplatin-related toxicity is 
a concern for many patients. In addition, not all patients with urothelial cancer are appropriate 
candidates for cisplatin therapy. For patients who are unable to receive cisplatin due to medical 
frailty 
or 
comorbidities, 
options 
include 
a 
carboplatin-based 
regimen 
(carboplatin plus gemcitabine, or carboplatin, gemcitabine, and paclitaxel), a non-platinum-based 
combination (eg, paclitaxel plus gemcitabine), immune checkpoint inhibitors, or for patients with 
select FGFR alterations, erdafitinib. For patients who are otherwise candidates for combination 
chemotherapy but are unable to receive cisplatin (eg, due to renal dysfunction, neuropathy, severe 
hearing loss, or heart failure), a combination of gemcitabine plus carboplatin is an alternative as 
the benefit of carboplatin-based therapy was demonstrated in European Organization for Research 
and Treatment of Cancer (EORTC) trial 30986 (Bellmunt 2020).
A meta-analysis of randomized controlled clinical trials compared chemotherapy regimens 
containing either cisplatin or carboplatin in combination with third generation antineoplastic 
agents including docetaxel, paclitaxel, and gemcitabine. Cisplatin-containing regimens were 
associated with a median survival of 9.1 months and a 1-year survival probability of 37%, while 
the carboplatin containing regimens were associated with a median survival of 8.4 months and a 
1-year survival probability of 34%. The risk of death was higher with carboplatin compared with 
cisplatin, although the difference was not statistically significant (HR=1.07, 95 % CI: 0.99 – 1.15, 
p=.100). These data support the interchangeable use of carboplatin or cisplatin in combination with 
standard of care antineoplastic agents (Ardizzoni 2007).
The pharmacokinetics and pharmacodynamics of cisplatin and carboplatin have been extensively 
studied. Monoexponential decreases and plasma half-lives of about 0.5 hour are seen following 
2-hour or 7-hour infusions of 100 mg/m2 of cisplatin (Food and Drug Administration [FDA] label). 
Plasma levels of carboplatin decay in a biphasic manner after a 30-minute intravenous infusion of 
300 mg/m2 to 500 mg/m2, with an initial plasma half-life (alpha) of 1.1 to 2 hours (n=6) and a post-
distribution plasma half-life (beta) of 2.6 to 5.9 hours (n=6). Cisplatin and carboplatin are mainly 
eliminated via urine, and there is little evidence to date that either undergoes enzymatic 
biotransformation

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Despite initial high response rates with conventional cisplatin-based chemotherapy regimens, 
5-year survival is suboptimal at 5% to 20% and associated with cumulative toxicities with longer 
exposure. Targeted therapy and checkpoint inhibitors have established a definite role in mUC, 
however subjects often progress quickly and could benefit from the addition of platinum-based
chemotherapy.
Combining platinum-based chemotherapy with a PD-1 therapy has been shown to improve 
progression-free survival in patients with metastatic urothelial cancer; however there still remains 
room for improvement. PD-1 agents alone have not shown adequate disease control without 
combining with chemotherapy. Although platinum-based chemotherapy remains a good option for 
patients, the cumulative toxicity of treatment with agents such as cisplatin or carboplatin can also 
prove difficult in managing a positive benefit/risk ratio.
1.7.
Overall Rationale for the Study
Rationale for combining erdafitinib with cetrelimab
Several observations point to the potential for 
 
. These include the potential for 
 
 
.
Urothelial carcinoma exhibits the third-highest mutation rate of all studied cancer types, behind 
NSCLC and melanoma (Alexandrov 2013). High tumor mutation burden is predicted to correlate 
with response to immunotherapies, due to the generation of neoantigens which may be recognized 
by the immune system. Recently, checkpoint inhibitors including atezolizumab, pembrolizumab, 
nivolumab, durvalumab, and avelumab have been approved for treatment of advanced urothelial 
carcinoma, with observed response rates of ~13-30%. Despite these improvements, however, most 
patients fail to benefit from checkpoint inhibition.
The response to checkpoint inhibitors is largely dependent on an existing anti-tumor T cell 
response, including sufficient T cell infiltration in the tumor microenvironment (Harlin 2009). 
However, not all urothelial cancers exhibit high T cell infiltration. A report classified the 
microenvironment of urothelial carcinoma tumors as T-cell-inflamed versus non-T-cell-inflamed. 
FGFR mutations were significantly enriched in the non-T-cell-inflamed group, with no FGFR 
pathway alterations identified in T-cell-inflamed samples (Sweis 2016). Differential response to 
immunotherapies have been observed in urothelial carcinoma based on bladder cancer molecular 
subtype, and the underlying immune landscape of these subtypes. Urothelial cancer, like breast 
cancer, can be classified via gene expression signature into luminal and basal subtypes (luminal 1, 
2, or basal 3, 4) (Cancer Genome 2014). Luminal 1 tumors are reported to be enriched for FGFR3 
mutations, and lacking in immune marker expression and immune cell infiltrate (Choi 2017). The 
luminal 1 subtype showed the lowest response rate to the anti-PD-(L)1 inhibitors atezolizumab 
and nivolumab compared with other bladder cancer subtypes (Rosenberg 2016); (Sharma 2017). 
Analyses of atezolizumab Phase 2 data showed PD-L1 expression on tumor infiltrating immune 
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cells was more pronounced in the basal subtype compared with the luminal subtype, with response 
to atezolizumab lowest in the luminal 1 group (Rosenberg 2016).
 
. This is consistent with the preliminary observation that patients 
with 
 
 
 
 
 
 Some agents may affect the expression of checkpoint inhibitory 
molecules such as PD-L1 on tumor cells or sensitize the tumor to immune-mediated killing via 
alternate mechanisms. The BRAF inhibitor vemurafenib has been shown to increase expression of 
tumor antigens gp100 and MART1, increase tumor T cell infiltration, and decrease tumor secretion 
of immunosuppressive cytokines, and PD-L1 expression (Hughes 2016); (Vanneman 2012). In a 
preclinical model of breast cancer, treatment with the FGFR1 inhibitor PD173074 resulted in 
increased CD4+ and CD8+ T cell and decreased myeloid derived suppressor cell (MDSC) 
infiltration in tumors (Ye 2014). These data suggest 
 
To inform the combination strategy of erdafitinib with a checkpoint inhibitor, the activity of 
erdafitinib alone or in combination with anti-PD-1 was assessed in a genetically engineered mouse 
model of lung cancer harboring mutations in FGFR and p53 (FGFR2K660N/p53R270H) 
(Palakurthi 2019). Vehicle control animals succumbed to disease after a median of 10.2 weeks, 
with anti-PD-1 treatment showing no benefit in this FGFR-mutant model (median survival of 
9.7 weeks). Erdafitinib treated animals survived a median 13.4 weeks, while the combination of 
erdafitinib plus anti-PD-1 prolonged survival to a median of 19.7 weeks (n=8 animals per group; 
p<0.0005 for the combination versus control, and p<0.004 for the combination versus erdafitinib 
alone, log rank test). Treatment with erdafitinib alone led to increased infiltration of CD4+ and 
CD8+ T cells in tumor (p=0.0233, and p=0.0008 versus vehicle, respectively), with concomitant 
decreases in the expression of the cell exhaustion markers Tim-3 and Lag-3 on CD8+ T cells 
(p=0.0171 versus vehicle). A decrease in the number of Tregs (Foxp3+/CD25+) in tumors was 
also observed (p=0.0191 versus vehicle). 
 
 
.
These results support the hypothesis that 
 
 
 in 
this setting.
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Rationale for addition of platinum (cisplatin or carboplatin) chemotherapy to erdafitinib and 
cetrelimab
Once diagnosed with metastatic disease, it is important for patients with urothelial cancer to 
initiate treatment without delay. The addition of platinum (cisplatin or carboplatin) chemotherapy 
to the erdafitinib/cetrelimab regimen presents a viable option for patients to treat metastatic 
disease immediately until targeted therapies and immunotherapies can demonstrate a response on 
their disease. It may also be less toxic as compared with multiple agent combination 
chemotherapy(ies).
Combining platinum (cisplatin or carboplatin) chemotherapy with targeted therapy and checkpoint 
inhibition may provide benefit to patients given the high response rate to chemotherapy in first 
line treatment, regardless of FGFR status. The addition of targeted therapy may deepen and 
lengthen that response.
Rationale for treatment in 1L mUC (Phase 2)
The management of metastatic urothelial cancer is driven by the global status of the patient 
including factors like ECOG PS Grade (0-1 versus 2), renal function (creatinine clearance [CrCl] 
≥60ml/min/1.73 m2 versus CrCl <60 ml/min/1.73 m2) and presence of comorbidities (eg, hearing 
loss, cardiac dysfunction). Renal function for cisplatin-eligible patients is typically defined as CrCl 
≥60mL/min/1.73 m2 versus cisplatin-ineligible CrCl <60 ml/min/1.73 m2 (Dogliotti 2007). 
Additionally, Grade 2 or higher hearing loss, ECOG PS of 2, or Grade 2 or higher peripheral 
neuropathy would also typically deem a patient ineligible for cisplatin (Galsky 2011). The global 
standard of care for both cis-eligible and cis-ineligible groups is combination chemotherapy. The 
standard of care for cisplatin-ineligible patients, includes combination chemotherapy of 
carboplatin and gemcitabine which has demonstrated an ORR of 39% for patients that have either 
ECOG 2 or CrCl <60 ml/min/1.73 m2, 26% for patients with both factors and 20% when adding 
the risk factor of visceral metastasis. Median PFS for cisplatin-ineligible patients is approximately 
3 months (Dogliotti 2007). Significant hematologic toxicity is observed with both 
gemcitabine/cisplatin and gemcitabine/carboplatin chemotherapy regimens; Grade 3-4 
neutropenia occurs in 34-45% of patients (Dogliotti 2007). Additionally, the risk of nephrotoxicity 
makes these therapies undesirable in up to half of patients with mUC who have concurrent renal 
insufficiency (Rosenberg 2005).
Erdafitinib monotherapy demonstrated efficacy in a subset of mUC patients without prior systemic 
therapy treated in a separate Phase 2 Global Open-Label Study 42756493BLC2001 of the efficacy 
and the safety of erdafitinib in subjects with metastatic or surgically unresectable urothelial cancer 
with FGFR genomic alterations (Loriot 2019). In that study, 10 cisplatin-ineligible patients with 
urothelial cancer who had no prior lines of systemic therapy in the metastatic setting were enrolled. 
In these 10 patients, median progression-free survival was 9.82 months (95% confidence interval 
[CI]: 1.38, 15.90) and median overall survival was 18.14 months (95% CI: 8.74, not evaluable). 
This efficacy with erdafitinib is comparable with standard front-line chemotherapy combination 
treatments albeit with fewer hematologic toxicities. The median overall survival was 13.8 months 
(95% CI, 12.3, 15.8) with gemcitabine and cisplatin and 14.8 months (95% CI, 13.2, 16.8) with 

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MVAC (Von der Maase 2000). In another study, median survival was 15.1 months on HD-MVAC 
and 14.9 months on M-VAC (Sternberg 2006). With gemcitabine and carboplatin, a median OS of 
9.3 months has been reported (DeSantis 2012). Among all mUC patients, irrespective of PD1 
status, a median overall survival of 15·9 months (95% CI, 10.4, not estimable) with atezolizumab 
(Balar 2017) and a median OS of 11.5 months (95% CI, 10.0, 13.3) with pembrolizumab (Balar 
2018) have been reported.
Based on the above data from BLC2001, cisplatin-ineligible patients with select FGFR alterations 
without prior systemic therapy are anticipated to have a beneficial effect from erdafitinib 
monotherapy. The combination of erdafitinib + cetrelimab (Arm B) is designed to estimate if and 
how much additive efficacy effect may be obtained with comparable or additional safety events. 
 
 
 
.
Randomization in Phase 2 helps in reducing bias when interpreting the efficacy and safety data in 
each arm. Analyses of safety and efficacy will be performed by each arm when there are 
approximately 90 response-evaluable subjects randomized in Phase 2. In the interim, a Data 
Review Committee consisting of experts internal and external to Janssen will monitor Phase 2 data 
on an ongoing basis.
Pembrolizumab and atezolizumab received accelerated approval in the 1LmUC cisplatin-ineligible 
population-based on single arm studies. In the IMvigor 210 study the ORR was 23% with PFS 
2.7 months. A similar ORR with pembrolizumab was observed in KEYNOTE-52 with a higher 
ORR in patients with higher PD-L1 expression. A recent review of ongoing 1L studies for both 
pembrolizumab and atezolizumab monotherapy indicated that pembrolizumab and atezolizumab 
may not work as well as chemotherapy in cisplatin-ineligible patients whose tumors have low 
expressions of PD-L1. As a result, the US FDA and European Medicines Agency (EMA) restricted 
the use of pembrolizumab and atezolizumab in first line setting for patients who are cisplatin-
ineligible to patients whose tumors have high PD-L1 expression. Another anti-PD1, durvalumab, 
which had received an accelerated approval from the FDA, missed its primary end points in the 
confirmatory Phase 3 DANUBE trial in frontline urothelial cancer and had to be withdrawn from 
this indication. 
Henceforth, the effect of monotherapy check-point inhibitors in frontline urothelial cancer is 
limited to a smaller subset of patients, and additional treatment options are needed. Currently there 
are a number of ongoing studies combining PD-L1 antibody therapy with chemotherapy, 
specifically gemcitabine and cisplatin, and also immunotherapy combination studies involving 
PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies in 1L mUC. New 
treatment options are needed in 1L mUC for the cisplatin-ineligible patient population with FGFR 
alterations.
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1.8.
Anticipated Benefits and Risks
Bladder cancer is the most common malignancy involving the urinary system with often limited 
OS in the metastatic setting. Despite the introduction of cisplatin-containing chemotherapy 
regimens, specifically cisplatin-gemcitabine and the MVAC regimen, nearly half of the subjects 
are ineligible leading to very poor survival rates in this unfit subject population due to high toxicity 
of cisplatin-containing regimens. Therefore, novel therapeutic options are required for the 
treatment of this subject population, specifically in the metastatic setting, representing an area of 
high unmet medical need.
1.8.1.
Anticipated Benefits and Risks for Erdafitinib and Cetrelimab
Erdafitinib showed anti-tumor effect in subjects with urothelial cancer with select FGFR 
alterations. In the Phase 1 study (Study 42756493EDI1001, N=187), the anti-tumor effect of 
erdafitinib was observed in subjects with urothelial cancer with select FGFR alterations, as well 
as other solid tumors. For all subjects with relapsed/refractory urothelial cancer, the ORR across 
dose levels was 40.0% (12/30 subjects). At the 9 mg dose level, the ORR was 70.0% (7/10 
subjects) for response-evaluable subjects with urothelial cancer who harbored select FGFR 
alterations. The global Phase 2 study (Study 42756493BLC2001) enrolled and treated subjects 
with select FGFR mutations and fusions with chemo-refractory and chemo-naïve advanced 
urothelial cancer who are ineligible for cisplatin (N= 210). The confirmed ORR by investigator 
assessment (CR+PR), 40.4% in the 8 mg once daily regimen. For subjects in the 8 mg once daily 
regimen whose dose was increased to 9 mg, the ORR was 48.4%. Response to erdafitinib was 
independent of age, sex, and baseline disease characteristics such as hemoglobin level or renal 
function. Subjects in the erdafitinib Phase 2 Study BLC2001 with a baseline CrCl less than 
60 mL/min (n=41) who received 8 mg erdafitinib daily (QD) had an ORR of 39%. Eleven subjects 
received no prior lines of therapy. The ORR for this group of subjects receiving erdafitinib as their 
first line of therapy (N=11) was 36%, and the disease control rate (CR+PR+SD) was 82%.
Based on data from Study BLC2001 erdafitinib was approved by the United States Food and Drug 
Administration (USFDA) in April 2019 for use in adult patients with metastatic urothelial 
carcinoma which has susceptible FGFR3 or FGFR2 genetic alterations and have progressed during 
or following at least one line of prior platinum-containing chemotherapy.
As of the clinical cutoff of 09 August 2019, the median follow-up for 101 subjects treated in the 
erdafitinib 8 mg regimen in Study 42756493BLC2001 was ~24 months. The median DoR was 
5.98 months. Thirty-one percent of responders had DoR ≥1 year. The median PFS was 
5.52 months. The median OS was 11.3 months. The 12 and 24-month survival rates were 49% and 
31%, respectively. Median treatment duration was 5.4 months.
As of 15 Jan 2019, in the FIH study 63723283LUC1001, 146 patients treated at the RP2D dose 
(240 mg Q2W) for cetrelimab were evaluable for response (Response evaluation criteria in solid 
tumors [RECIST] 1.1 per investigator assessment). More than half of this group was comprised of 
patients with advanced melanoma (n=50) and non-small cell lung cancer (NSCLC; n=30). Other 
tumor types enrolled to the study included high levels of microsatellite instability/deficient 
mismatch repair (MSI-H/dMMR) colorectal cancer (CRC) (n=41), gastric esophageal (10), small 

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cell lung (n=9), bladder (n=4) and renal (n=1). The ORR was 50% (80% confidence interval [CI] 
33-67) in patients with PD-L1-high NSCLC (n=18) and 55% (80% CI 32-76) in patients with >1% 
PD-L1-positive melanoma (n=11), consistent with the ORRs observed in approved PD-L1 
inhibitors (Rutkowski 2019). In both of those groups more than half of the response-evaluable 
subjects obtained clinical benefit (CR+PR+SD) for more than 6 months (67% and 73%, 
respectively). At the time of the data cut one of the bladder cancer patients was considered to have 
a response per the immune-related response criteria (Wolchok 2009), although was considered PD 
per RECIST 1.1.
Immune checkpoint inhibitors, such as anti-PD-1 monoclonal antibodies, target proteins that 
enhance the response of the immune system to tumor cells. By stimulating the endogenous immune 
system, however, there is the potential for adverse effects on other tissues by way of immune cell 
activation and inflammatory mechanisms. Treatment with anti-PD-1 monoclonal antibodies have 
been linked to irAEs which require close and more frequent monitoring, and early intervention 
such as administration of immunosuppressants. Immune-related endocrinopathies such as 
hypothyroidism and adrenal insufficiency may require endocrine replacement therapy. Other 
immune-related risks already identified with other PD-1 antibodies include gastrointestinal AEs 
such as colitis and diarrhea, pneumonitis, renal AEs such as nephritis and acute renal failure, 
hepatic AEs such as hepatitis and liver enzyme elevations, and dermatitis. The safety profile of 
currently approved anti-PD-1 antibodies (eg, atezolizumab and pembrolizumab), is manageable 
with most AEs being Grade 1 or Grade 2 in severity. Immune-related AEs typically resolve after 
systemic treatment with corticosteroids or discontinuation of study treatment.
In the FIH study 63723283LUC1001, treatment with cetrelimab showed overall similar toxicity 
profile when compared to already approved compounds targeting the PD-1/PD-L1 pathway. 
Treatment with erdafitinib in the Phase 1 (Study 42756493EDI1001) and a Phase 2 trial (Study 
42756493BLC2001) was linked to hyperphosphatemia, diarrhea, dry mouth, asthenia, stomatitis, 
constipation, and decreased appetite as the most frequently reported AEs, most of which were 
Grade 1 or 2 in severity and treatment was well tolerated.
Based on currently available clinical data from erdafitinib and cetrelimab as monotherapies as well 
as preliminary data from this study in Section 1.5.2, the safety profiles for erdafitinib and 
cetrelimab are anticipated to remain manageable. Given the potentially complementary 
mechanisms of action of erdafitinib and cetrelimab (PD-1 inhibitor), it is hypothesized that this 
combination will provide increased efficacy relative to either agent alone in patients with urothelial 
cancer. As stated in Section 1.5.2 no DLTs were observed in any of the cohorts and the 
recommended Phase 2 dose (RP2D) was established as 8 mg erdafitinib orally once a day with 
up-titration to 9 mg based on C1D15 phosphate level + 240 mg cetrelimab IV Q2W.
After the RP2D was determined, the DRC met (ad hoc) at the request of the sponsor to review 
safety data as of 08 January 2020 with a particular focus on stomatitis at the RP2D. At that time 
stomatitis occurred in 70% of patients (7/10) at the RP2D which was higher than the frequency 
with erdafitinib monotherapy. The average time to onset was approximately 20 days which was 
sooner than that for erdafitinib monotherapy. The majority of patients experiencing mucositis at 

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erdafitinib + cetrelimab + platinum chemotherapy cohort. In the first line patients with metastatic 
urothelial cancer, platinum-based chemotherapies are standard of care, and have AE profile 
consistent with 2 or more chemotherapeutic agents. Cisplatin-ineligible first line patients are 
treated with other chemotherapy combinations, some including carboplatin, or with approved 
PD1-inhibitors. In patients diagnosed with metastatic disease, the addition of platinum 
chemotherapy could provide a shorter time to response, to give time for targeted therapies and 
immunotherapies to demonstrate a response on their disease. A combination of 
cisplatin/carboplatin, cetrelimab and erdafitinib is anticipated to provide a comparable or better 
efficacy than platinum-based chemotherapy (combination of 2 chemotherapies) or PD-1 inhibitor
monotherapy in first line setting.
Platinum chemotherapies (cisplatin or carboplatin) are known to have similar but varying 
frequency of AEs such as thrombocytopenia, leukopenia, anemia, vomiting, nausea, 
nephrotoxicity, neurotoxicity and ototoxicity, when used as monotherapies. Although erdafitinib, 
cetrelimab and platinum chemotherapies predominantly have non-overlapping toxicities, platinum 
chemotherapies are also associated with a number of electrolyte disorders, including 
hypophosphatemia (Oronsky 2017). Possible mechanisms of hypophosphatemia in platinum-
treated patients include increased renal excretion due to tubular dysfunction, other electrolyte 
disorders (magnesium, calcium), deprivation due to cachexia, vomiting and diarrhea. The 
frequency of hypophosphatemia in advanced cancer patients can be high, with as many as 49.4% 
of patients experiencing phosphate levels <2.5 mg/dL and 22.9% of patients experiencing 
phosphate levels <2.0 mg/dL (Yoshida 2017). Erdafitinib, on the other hand, induces 
hyperphosphatemia. For erdafitinib, serum phosphate increase is a biomarker of target engagement 
as well as an expected AE. PD interactions are expected between erdafitinib and platinum 
chemotherapy, as both have opposite effect on serum phosphate. PD assessments will be 
characterized in this study to quantify the PD interaction between erdafitinib, cetrelimab, and 
platinum chemotherapies.
In conclusion, the benefit-risk balance with the addition platinum chemotherapies is anticipated to 
be favorable.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
The primary, secondary, and exploratory objectives and endpoints for the Phase 1b erdafitinib + 
cetrelimab cohort are described in Section 2.1 of Appendix 1.
The primary, secondary, and exploratory objectives and endpoints for the Phase 1b erdafitinib + 
cetrelimab + platinum chemotherapy cohort are described in Section 2.1 of Appendix 2.
The primary, secondary, and exploratory objectives and endpoints for the Phase 2 erdafitinib +/-
cetrelimab cohort of the study are described in Section 2.1 of Appendix 3.

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2.2.
Hypotheses
The hypothesis for the Phase 1b erdafitinib + cetrelimab cohort is described in Section 2.2 of 
Appendix 1.
The hypothesis for the Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort is 
described in Section 2.2 of Appendix 2.
The hypothesis for the Phase 2 erdafitinib +/- cetrelimab cohort of the study is described in 
Section 2.2 of Appendix 3.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This study is an open-label, multicenter, Phase 1b-2 study to establish the RP2D for erdafitinib in 
combination with cetrelimab +/- platinum (cisplatin or carboplatin) chemotherapy, and the safety 
of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b, and to 
evaluate the safety and efficacy of the RP2D of erdafitinib + cetrelimab versus erdafitinib in 
Phase 2, in subjects with advanced urothelial cancer with select FGFR gene alterations.
An overview of dose levels of the Phase 1b erdafitinib + cetrelimab cohort and Phase 1b erdafitinib 
+ cetrelimab + platinum (cisplatin or carboplatin) chemotherapy cohort is described in Figure 1
and Figure 2, respectively. An overview of the Phase 2 dose expansion cohort is described in 
Figure 3.
Subjects enrolled in the Phase 1b erdafitinib + cetrelimab cohort may have received any number 
of lines of prior therapy, subjects enrolled in Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort will have had no prior systemic therapy for metastatic disease, and subjects 
enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be 
cis-ineligible (see the Inclusion Criteria 6.1 in Section 4.1). All subjects will undergo molecular 
testing during Screening to assess for select FGFR alterations (as defined in Table 4).
Table 4:
Molecular Eligibility Based Upon the Following FGFR Alterations a, b
1 of the following fusions:
OR
1 of the following FGFR3 gene 
mutations:
FGFR2-BICC1
FGFR2-CASP7
R248C
S249C
FGFR3-
TACC3
FGFR3-
BAIAP2L1
G370C
Y373C
a Phase 1b erdafitinib + cetrelimab cohort and Phase 2 erdafitinib +/- cetrelimab cohort: tumors must have at 
least one gene fusion or gene mutation as defined above.
b Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: up to 3 subjects in each erdafitinib + 
cetrelimab + chemotherapy cohort at each dose level will be wild-type. Wild-type is defined as subjects 
without FGFR gene alteration and subjects with FGFR gene alterations other than the select FGFR alterations 
as defined above. All other subjects must have at least one select FGFR alteration as defined above.
Tissue provided at Screening will be used to assess 
 
(exploratory). The study consists of 2 parts: Phase 1b, which 
is a dose escalation part to identify the safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib 
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+ cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Phase 2, which is a dose 
expansion part in which the erdafitinib monotherapy and the RP2D regimen of the erdafitinib + 
cetrelimab combination are evaluated to further characterize safety and clinical activity. In Phase 
2, subjects will be randomized at a 1:1 ratio for treatment with erdafitinib monotherapy (Arm A) 
or with the erdafitinib + cetrelimab combination therapy (Arm B). Randomization will be stratified 
by ECOG PS (0-1 versus 2). A target of approximately 90 subjects will be enrolled in Phase 2, 
with the potential to enroll approximately 160 overall subjects in the study depending on the dose 
levels studied in Phase 1b.
Paired biopsies at Screening and C2D1 are optional. The biopsy upon PD is also optional for all 
subjects. High-risk areas of metastases such as brain, pancreas, and lung should not be considered 
as an accessible site for biopsy. Biopsies will be collected to aim to have a minimum of 15 
evaluable biopsy pairs.
Subject participation will include: Screening Phase (detailed in Section 9.1.2), during which 
subject eligibility (including molecular eligibility) will be reviewed prior to administration of the 
first dose of erdafitinib in combination with cetrelimab, and platinum chemotherapy (where 
applicable); a Treatment Phase (detailed in Section 9.1.3) that will start at the first dose and 
continue until treatment is discontinued (as defined in Section 10.2); and a Follow-up Phase 
(detailed in Section 9.1.4). The end of the study is defined as the last study assessment for the last 
subject on study or if the sponsor terminates the study, whichever comes first (see Section 17.9).

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3.1.1.
Phase 1b
Figure 1: Overview of the Phase 1b: Erdafitinib + Cetrelimab Cohort
Refer to Section 3.1.1 of Appendix 1 for additional information regarding the study design of the 
Phase 1b erdafitinib + cetrelimab dose levels. Refer to Section 6.2.1 for a description of the 
erdafitinib dose titration guidelines.

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Figure 2: Overview of the Phase 1b: Erdafitinib + Cetrelimab + Platinum Chemotherapy Cohort
Refer to Section 3.1.1 of Appendix 2 for additional information regarding the study design of the 
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort.

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3.1.2.
Phase 2
Figure 3: Overview of the Phase 2: Erdafitinib +/- Cetrelimab Cohort
Refer to Section 3.1.2 of Appendix 3 for additional information regarding the study design of the 
Phase 2 erdafitinib +/- cetrelimab (Dose expansion) cohort.
3.1.3.
Schedule of Activities for All Ongoing Subjects After the End of 
Study Data Collection Timepoint (Protocol Amendment 5)
Following Amendment 5, once the end of study data collection timepoint has been achieved, 
subjects who continue to benefit from study treatment(s), as determined by their investigator, may 
continue to receive access to study treatment(s) on this study, with reduced data collection (see 
Section 17.9.1), either via a long-term extension roll-over study or any other post-trial access 
program, when permitted by local regulations.  Provision may continue until the subject can 
commercially access study treatment(s) within the local healthcare system, until a decision is made 
not to pursue the studied indication, until the investigator decides it is in the best interest of the 
subject that study treatment(s) be discontinued, or until 2 years after local marketing authorization 
for is obtained for the studied indication, whichever comes first.
3.2.
Study Design and Starting Dose Rationale
Rationale for Erdafitinib Dose and Regimen Selection
The recommended monotherapy dose for erdafitinib is based on clinical activity and safety data in 
the Phase 2 urothelial cancer study 42756493BLC2001 and subsequent PK/PD modeling.
Rationale for Cetrelimab Dose and Regimen Selection
 
 
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Rationale for Combination of Erdafitinib and Cetrelimab
The study design is intended to test the hypothesis that the combination of erdafitinib with 
cetrelimab will lead to an improved anti-tumor effect with an overall favorable toxicity profile. As 
described in Section 1.8.1, these data indicate that erdafitinib monotherapy, as reported for other 
 
 The results of a study of an FGFR-mutant mouse 
model 
 
 
 
 
 
 
 
 
.
Rationale for Combination of Erdafitinib, Cetrelimab, and Platinum Chemotherapy
The addition of platinum (cisplatin or carboplatin) chemotherapy to the erdafitinib/cetrelimab 
regimen presents a viable option for patients to treat metastatic disease immediately until targeted 
therapies and immunotherapies can demonstrate a response on their disease.
Combining platinum chemotherapy with targeted therapy and checkpoint inhibition may provide 
benefit to patients given the high response rate to chemotherapy in first line treatment, regardless 
of FGFR status. The addition of targeted therapy may deepen and lengthen that response rate.
Rationale for the Subject Population
In this study, erdafitinib is approved by the USFDA for use in adult patients with locally advanced 
or metastatic urothelial carcinoma which has susceptible FGFR3 or FGFR2 genetic alterations and 
have progressed during or following at least one line of prior platinum-containing chemotherapy. 
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In the erdafitinib Phase 2 Study BLC2001, response to erdafitinib in patients with locally advanced 
or metastatic urothelial carcinoma was independent of age, sex, and baseline disease characteristics 
such as hemoglobin level or renal function. Response was also consistent regardless of the number 
of lines of prior systemic therapy; chemo-relapsed/refractory subjects with 1 or 2 or more lines of 
prior systemic therapy all responded to erdafitinib treatment. ORRs by investigator for subjects 
who received prior systemic therapy ranged from 36% to 60% and DCR by investigator ranging 
from 75% to 90% by number of prior systemic therapy lines. Subjects in Study BLC2001 with a 
baseline CrCl less than 60 mL/min (n=41) who received 8 mg erdafitinib QD had an ORR of 39%. 
Eleven subjects received erdafitinib as first line therapy in Study BLC2001. The ORR for this 
group of subjects was 36% (95% CI 7.9, 64.8), and the disease control rate (CR+PR+SD) was 82% 
(95% CI 59, 100). This supports the hypothesis that patients with FGFR alterations may benefit 
from first line treatment with erdafitinib. 
 
 
Progress has been made in the clinical management of urothelial cancer by establishing 
comprehensive, multi-modality treatment regimens; however, the prognosis for advanced disease 
has not improved substantially. Cytotoxic chemotherapies as single agents or in combination with 
PD-1 have made advances for this patient population, however molecular profiling has established 
a definite role for therapy in a subset in mUC patients. In patients diagnosed with metastatic 
disease, the addition of platinum chemotherapy could provide a shorter time to response, to give 
time for targeted therapies and immunotherapies to demonstrate a response on their disease. There 
is an interest in determining if the combination of erdafitinib (targeted therapy), in combination 
with cetrelimab (PD-1) and cisplatin/carboplatin chemotherapy demonstrates clinical activity.
Rationale for Biomarker Collection
The biomarker assessments will evaluate the 
 
 
Based on data from single-agent studies, blood and 
tumor samples will be collected to explore biomarkers 
 
 
Rationale for PK and PD Assessment
Potential for PK-mediated drug-drug interaction:
Due to the lack of common elimination pathways, no relevant PK interactions are expected 
between erdafitinib and cetrelimab. The PK assessments of both drugs will be characterized in this 
study to confirm the consistency of systemic exposure of the 2 compounds given in combination 
with those obtained following the single-agent administrations.
Since platinum-based chemotherapies are not eliminated by CYP enzymes but mainly via renal 
excretion, and are not perpetrators of CYP enzymes, the risk of enzyme-based drug-drug 
interaction (DDI) between erdafitinib and these platinum chemotherapy agents is low. Based on 
CCI
CCI
CCI

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in vitro studies, erdafitinib could be a potential inhibitor of OCT2 transporter (USPI). Since both 
cisplatin and carboplatin are substrates of OCT2, the potential transporter-based DDI between 
erdafitinib and these chemotherapy agents need to be characterized.
Interaction between platinum chemotherapy agents and cetrelimab is expected to be low given the 
different elimination pathway. Conversely, chemotherapy agents are not expected to affect 
cetrelimab clearance, which is mainly governed by protein catabolism pathways. Nevertheless, the 
PK of cisplatin and carboplatin, in addition to erdafitinib and cetrelimab, will be evaluated in this 
study, so that DDI, if any, between these drugs can be explored. As cisplatin and carboplatin are 
intended to be used in combination with erdafitinib and cetrelimab in this study, this evaluation is 
particularly important since platinum chemotherapy agents have narrow therapeutic range (FDA 
Guidance 2012).
Potential for PD-mediated drug-drug interaction (serum phosphate):
Due to the absence of cetrelimab effect on serum phosphate to date, no relevant PD interactions 
are expected between erdafitinib and cetrelimab. However, PD interactions are expected between 
erdafitinib and platinum (cisplatin or carboplatin) chemotherapies, as both have opposite effect on 
serum phosphate. PD assessments will be characterized in this study to quantify the PD interactions 
between erdafitinib, cetrelimab, and platinum chemotherapies.
Erdafitinib-induced hyperphosphatemia is a well characterized phenomenon. For erdafitinib, an 
increase in serum phosphate is a biomarker of target engagement as well as an expected AE. To 
avoid interference with the determination of the initial dose increase based on serum phosphate 
levels, it is recommended to avoid co-administration of serum phosphate level-altering agents with 
erdafitinib before the initial dose increase period (Days 14 to 21). So far, no effect of cetrelimab 
on serum phosphate has been observed. Platinum chemotherapies however lead to a number of 
electrolyte disorders, including hypophosphatemia (Oronsky 2017). Possible mechanisms of 
hypophosphatemia in platinum-treated patients include increased renal excretion due to tubular 
dysfunction, other electrolyte disorders (magnesium, calcium), deprivation due to cachexia, 
vomiting and diarrhea. The frequency of hypophosphatemia in advanced cancer patients can be 
high, with as many as 49.4% of patients experiencing phosphate levels <2.5 mg/dL and 22.9% of 
patients experiencing phosphate levels <2.0 mg/dL (Yoshida 2017).
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D
For the Phase 1b erdafitinib + cetrelimab cohort, refer to Section 3.3 of Appendix 1. For the Phase 
1b erdafitinib + cetrelimab + platinum chemotherapy cohort, refer to Section 3.3 of Appendix 2.
3.3.1.
Definition of Dose-Limiting Toxicity for Phase 1b (Dose Escalation)
For the Phase 1b erdafitinib + cetrelimab cohort, refer to Section 3.3.1 of Appendix 1. For the 
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort, refer to Section 3.3.1 of 
Appendix 2.

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3.3.2.
Determination of the Phase 1b RP2D Regimen and Alternative Dosing 
Schedules
For the Phase 1b erdafitinib + cetrelimab cohort, refer to Section 3.3.2 of Appendix 1. For the 
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort, refer to Section 3.3.2 of 
Appendix 2.
3.4.
Study Evaluation Team
Subject safety will be monitored throughout the Phase 1b part of the study by the SET established 
by the sponsor until the RP2D of erdafitinib and cetrelimab is determined. This committee will 
monitor all available treatment-emergent data (eg, PK, PD, safety) on an ongoing basis throughout 
the study to ensure the safety of subjects enrolled in this study.
The SET will be chaired by the sponsor’s Molecule Responsible Physician and membership will 
include the sponsor Study Responsible Physician, a sponsor clinical scientist, a subset of the study 
principal investigators, safety physician (sponsor’s Safety Management Team chair), statistician, 
and clinical pharmacologist, along with additional sponsor staff, as appropriate. The team will 
meet at regular frequency throughout study conduct. In addition, SET meetings may be conducted 
at any time during the study at the request of either the sponsor or investigator(s) to assess 
emerging safety signals. Documentation of meeting outcomes will be maintained by the sponsor. 
Decisions will be communicated to investigators and decisions with the potential to affect subject 
safety (eg, unfavorable change in benefit/risk assessment) will also be promptly communicated to 
regulatory authorities as required.
Dose escalation decisions in Phase 1b of the study will be made by the SET. The schedule of dose 
escalation meetings will depend on the frequency of DLTs and if/when the MTD or maximum 
administered dose is determined or when an RP2D is determined. The SET can evaluate up-titrated 
and non-up-titrated subjects separately based on the totality of the emerging safety data. 
Cumulative safety data will be routinely assessed by the DRC after the RP2D of erdafitinib and 
cetrelimab is determined.
Prior to the determination of the RP2D of erdafitinib and cetrelimab, the SET may also decide on 
modifications in study conduct such as additional dose cohorts/dose levels if required or stop 
further enrollment into 1 or more of the cohorts/dose levels if treatment-emergent toxicity is 
determined to result in an unfavorable change in subject risk/benefit. Enrollment may be 
temporarily held, if needed, for the SET to evaluate the emerging data.
4.
SUBJECT POPULATION
For the Phase 1b part of the study, refer to Section 4 of Appendix 1 or Section 4 of Appendix 2, as 
appropriate.
For the Phase 2 cohort of the study, refer to Section 4 of Appendix 3.

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5.
TREATMENT ALLOCATION AND BLINDING
For the Phase 1b part of the study, refer to Section 5 of Appendix 1 or Section 5 of Appendix 2, as 
appropriate.
For the Phase 2 cohort of the study, refer to Section 5 of Appendix 3.
6.
DOSAGE AND ADMINISTRATION
For the Phase 1b part of the study, refer to Section 6 of Appendix 1 or Section 6 of Appendix 2, as 
appropriate.
For the Phase 2 cohort of the study, refer to Section 6 of Appendix 3.
6.1.
Dose Combination Cohorts/Arms
For the Phase 1b part of the study, refer to Section 6.1 of Appendix 1 or Section 6.1 of Appendix 2, 
as appropriate.
For the Phase 2 cohort of the study, refer to Section 6.1 of Appendix 3.
6.2.
Administration of Erdafitinib
Erdafitinib will be provided as tablets for oral administration. 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. Each dose should be taken at approximately the same 
time each day in the morning with or without food. Should an alternative dosing schedule be used 
in the study, subjects will be instructed to take their assigned dose of the study drug orally on that 
alternative dosing schedule.
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, including the subject’s diary card, and the electronic 
case report form (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 cannot be re-issued in this study or outside the study 
(follow study drug accountability guidelines in the Site Investigational Product and Procedures 
Manual [SIPPM]).
If a dose is missed, 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. Missed doses will not be replaced and the next dose will remain unchanged. 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 subject’s diary 
card and the eCRF.

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6.2.1.
Dose Up-titration Guidelines
Based on emerging safety data, on 12 May 2020, the DRC recommended to remove the 
requirement for up-titration from the erdafitinib + cetrelimab combination in Arm B. The DRC 
also made a recommendation to close Dose level 2 in Phase 1b and focus enrollment efforts into 
the Phase 2 part of the study. Therefore, DL2 will be closed. DL2B will remain open and will 
include up-titration of erdafitinib based on serum phosphate concentration from a blood sample on 
Day 15 and the absence of significant erdafitinib-related toxicity on C1D15 as determined by the 
investigator.
Subjects assigned to Dose Level DL2 or DL2B in Phase 1b or Arm A and in Phase 2, will be 
assigned to the up-titrated dose level of erdafitinib based on serum phosphate concentration from 
a blood sample on Day 15 and the absence of significant erdafitinib-related toxicity on C1D15 as 
determined by the investigator. There is no up-titration in either of the erdafitinib + cetrelimab + 
platinum (cisplatin or carboplatin) chemotherapy cohort or Arm B of the Phase 2 erdafitinib +/-
cetrelimab cohort.

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 levels until it returns 
to less than 7.00 mg/dL (<2.25 mmol/L) while initiating treatment with a phosphate binder 
such as sevelamer (see Table 8 for detailed guidelines regarding further treatment).

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 8 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 without concomitant phosphate binder such as sevelamer.
6.2.2.
Dose Modification, Dose Delays, and Retreatment Criteria for 
Erdafitinib
Treatment with erdafitinib should be discontinued or modified based on toxicity as described in 
Table 5 and the specific guidance below. For eye, skin/nail, dry mouth/mucositis, liver, and 
phosphate toxicities, specific management guidelines are provided in Sections 6.2.3.1 through 
Section 6.2.3.7. This guidance is only intended for toxicity management. 

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Table 12:
General Prophylaxis & Guidelines for Management of Nail Discoloration/Loss/Ridging 
(Onycholysis/Onychodystrophy)
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)
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 of infection (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, or
sulfamethoxazole/ trimethoprim BID)
AND
o
topical antifungal lacquer daily for
6+ weeks (ciclopirox olamine 8% OR
efinaconazole 10% OR amorolfine 5%
weekly OR bifonazole/urea ointment
daily)

Silver nitrate application weekly AND topical 
antibiotics AND vinegar soaksa
Grade 3
Hold study drug, with reassessment in 
1-2 weeks.
When resolves to ≤Grade 1 or baseline,
restart at 1 dose level below in
consultation with the medical monitor.
Silver nitrate application weekly AND topical
antibiotics AND vinegar soaks.a
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/trimethoprimBID).
For cases of severe/refractory infection consider
intravenous antibiotics.
Consider dermatological or surgical evaluation.
Grade 4
Discontinue study drug.
Evaluation and therapy as clinically indicated.
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

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
A treatment-related AE does not resolve to Grade ≤1 within 12 weeks of the last dose of study 
drug unless otherwise agreed to by the sponsor medical monitor and the investigator based on 
evidence of clinical benefit

Any non-hematological treatment-related event occurs a second time at Grade 3 severity

Grade 3 (or recurrent Grade 2) pneumonitis

Grade 3 nephritis with creatinine ≥3 xULN

Grade 3 elevation of AST or ALT >5 xULN or total bilirubin >3 xULN

For subjects with baseline Grade 2 elevation of AST or ALT due to liver metastasis, only 
Grade ≥3 elevations that are ≥50% of baseline for ≥7 days will require discontinuation of 
study treatment

Liver metastasis with baseline Grade 2 elevation of AST or ALT, hepatitis with AST or ALT 
increase 50% and lasts 1 week

Grade 3 IRRs

Immune-mediated encephalitis.
If a subject's cetrelimab is discontinued, this will not result in automatic withdrawal of the subject 
from the study. The subject may continue on the other study treatments(s). Following cetrelimab 
discontinuation, the subject should complete the End-of-Treatment Visit as described in Time and 
Events Schedule and Section 9.1.3. Once a subject discontinues treatment, the subject may not be 
retreated with the study drug.
Following Amendment 5 and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and only SAEs must be reported through the company safety repository.
6.3.4.
Guidelines for Management of Immune-Related Adverse Events and 
Adverse Events of Clinical Interest
Therapy with immuno-oncology agents such as cetrelimab can lead to specific irAEs that differ in 
nature, severity and duration as compared to AEs caused by agents with a different mode of action. 
Early recognition and management of these irAEs may mitigate more severe/subsequent toxicity. 
However, differential diagnoses including non-inflammatory etiologies as well as the impact of 
the underlying malignant disease and/or concomitant medication should be evaluated according to 
standard medical practice.
Management algorithms have been developed to assist investigators in assessing and managing 
specific irAEs following administration of nivolumab (Knowles 2015); (Nivolumab 2016) and 
pembrolizumab (Keytruda® 2014); (Oken 1982). These guidelines are presented below and should 
be followed for cetrelimab. In addition to the management algorithms provided in following 
sections, it is recommended that irAEs are managed according to the general treatment guidelines 
outlined for ipilimumab (Ipilumumab 2015). These guidelines recommend the following:
1. Subjects should be evaluated to identify any alternative etiology.
2. In the absence of a clear alternative etiology, all events of an inflammatory nature should be 
considered immune-related.

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institutional guidelines for the treatment of anaphylaxis. Remain at bedside and monitor subject 
until recovery from symptoms. In the case of late-occurring hypersensitivity symptoms 
(eg, appearance of a localized or generalized pruritus within 1 week after treatment), 
symptomatic treatment may be given (eg, oral antihistamine, or corticosteroids).
General
Prophylactic medications (after initial event): diphenhydramine 50 mg (or equivalent) and/or 
paracetamol 325 to 1000 mg (acetaminophen) at least 30 minutes before additional study drug 
administrations; if necessary, corticosteroids (recommended dose: up to 80 mg of IV 
methylprednisolone or equivalent) may be used.
Appropriate resuscitation equipment should be available in the room and a physician readily 
available during the infusion of study drug.
6.3.4.12.
Monitoring During and After Study Drug Administration
Subjects should be carefully observed during cetrelimab infusions. Trained study staff at the clinic 
should be prepared to intervene in case of any IRRs occurring, and resources necessary for 
resuscitation (eg, agents such as epinephrine and aerosolized bronchodilator, also medical 
equipment such as oxygen tanks, tracheostomy equipment, and a defibrillator) must be available 
at bedside. Attention to staffing should be considered when multiple subjects will be dosed at the 
same time.
If an infusion-related reaction develops, then the infusion should be temporarily interrupted or 
slowed down. Guidelines outlined in Section 6.3.4.11 must be followed to manage IRRs.
Subjects should be monitored for at least 2 hours after the completion of the first infusion and may 
be discharged if considered clinically stable and all other study procedures have been completed. 
The investigator will determine the duration of safety monitoring for subsequent administrations.
6.4.
Administration of Platinum Chemotherapy (Cisplatin or Carboplatin)
Refer to Section 6.4 of Appendix 2.
6.5.
Toxicity Due to One Study Drug and Continuation of Treatment
The dose modification guidelines described in Section 6.2, Section 6.3, and Section 6.4.4 are to be 
used throughout both phases of the study, as applicable. If a subject experiences several toxicities 
and there are conflicting recommendations, the most conservative dose adjustment recommended 
should be followed (dose reduction appropriate to the most severe toxicity). The recommendation 
to discontinue study therapy may apply to all study drugs. However, in cases in which the 
investigator and the study sponsor agree that the observed drug-related AE leading to 
discontinuation was most probably related to 1 of the study drugs, continuation of therapy with the 
other study drug(s) is permitted after discussion with the medical monitor.
7.
TREATMENT COMPLIANCE
The investigator or designated study personnel will maintain a log of the amount of study drug 
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. A 
diary card will be given to the subject to record intake at home. On days when the subject visits 
the study center for dose administration or PK sampling, the investigator or designee will supervise 

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administration of the study drug and the exact time of administration will be recorded in the eCRF. 
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.
If appropriate, site visits may be replaced with telephone visits during a national disaster, with site 
visits resuming as soon as possible thereafter. Please refer to Attachment 10 for additional 
guidance on study conduct for enrolled subjects during a national disaster.
8.
CONCOMITANT THERAPY
Following Amendment 5, and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and only concomitant therapies associated with an SAE must be reported 
through the company safety repository.
Therapies are to be recorded at the time of Screening (within 28 days prior to the first dose of study 
drug), throughout the study, and up to 100 days after the last dose of study drug in the appropriate 
section of the eCRF. Once a subject starts a subsequent systemic anticancer therapy, data collection 
will be limited to concomitant medications used to treat ongoing or newly developed Grade 2 
immune-related AEs considered related to cetrelimab.
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 eCRF. Caution should be exerted for subjects taking anticoagulant therapies. 
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
Throughout the study, investigators may prescribe concomitant medications or treatments 
(including nutritional support, correction of metabolic disorders, optimal symptom control, and 
pain management) deemed necessary to provide adequate supportive care. Concurrent use of 
hormones for non-cancer related conditions (eg, insulin for diabetes and hormone replacement 
therapy) is acceptable. Concomitant medications (eg, acetaminophen/paracetamol or 
diphenhydramine) deemed necessary by the investigator to provide adequate prophylaxis and 
management of IRRs are allowed. Refer to Section 6.3.4 for guidance on medications to manage 
immune-related toxicities.
In addition, the following medications may be administered during the study:

Standard 
supportive 
care 
therapies 
(antiemetics, 
antidiarrheals, 
anticholinergics, 
antispasmodics, antipyretics, antihistamines, analgesics, antibiotics and other antimicrobials, 
histamine receptor [H2] antagonists or proton pump inhibitors, and other medications intended 
to treat symptoms or signs of disease) as clinically indicated, according to institutional 
standards and as deemed necessary by the investigator.

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Molecular Eligibility Screening Period
The Molecular Eligibility Screening Period starts with the signing of a molecular eligibility 
informed consent form (ICF) and can occur at any time prior to administration of study drug 
(≥28 days prior to administration of the study drugs). Consent for molecular screening (but not 
full-study screening) may be performed remotely including consent by telephone or video 
consultation, unless not permitted according to local guidance.
Subjects may by-pass the molecular Screening Phase of Study BLC2002 if they have already been 
molecularly screened for FGFR alterations by the central laboratory in the context of another 
Janssen-sponsored study.
Molecular eligibility will be determined for all subjects by the presence (or absence) of select 
FGFR mutations and fusions as described in Table 4.
During the Molecular Eligibility Screening Period, there are 2 approaches that may be used to 
determine FGFR status for this study, ie, central molecular screening or local test results:
1) Central Molecular Screening (Submission of Tissue and Blood Samples Required*)
FGFR analysis of tissue and blood by the central laboratory. Archival tumor tissue or a fresh 
biopsy sample and a blood sample will be sent to the central laboratories for testing. Blood and 
tissue samples do not need to be submitted concurrently; samples may be submitted as they become 
available during the Molecular Eligibility Screening Period. The central laboratory will evaluate 
subjects for molecular eligibility (where applicable) by analyzing tumor and blood specimens for 
the presence of select FGFR mutations and gene fusions. The sponsor or central 
laboratory/designee will communicate results of the molecular testing to the site. If a biopsy is 
required to perform FGFR analysis, the subject must consent to this procedure utilizing the main 
study consent form. 
Subjects may enroll in the study if at least one sample (tissue or blood) results in identification of 
a study-eligible FGFR alteration, however if a subject enrolls based on blood testing, a tissue 
sample must be submitted for central confirmatory testing.
2) Local report with evidence of a study-eligible FGFR mutation or fusion (or for Phase 1b 
erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy cohort proof 
of FGFR testing, independent of FGFR status). Local test results (from tissue or blood) or 
the Qiagen Therascreen FGFR RGQ RT-PCR test (from tissue) performed at a CLIA-certified 
or regional equivalent laboratory may be used to meet molecular eligibility. A copy of the test 
report documenting the FGFR result must be included in the subject records and a de-identified 
copy must also be submitted to the sponsor for confirmation of eligibility.

If a subject is enrolled based on local testing, a tissue and blood 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 retrospective 
confirmation testing, the site should contact the sponsor prior to proceeding to full-study 
screening.

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
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. 
Concordance between local and central testing, where applicable, will be reviewed 
periodically by the sponsor.
If a subject meets the molecular eligibility criteria (where applicable), he or she may continue 
study screening under the Full-Study ICF for determination of full-study eligibility.
Full-Study Screening Period
The Study Screening Period (for full-study eligibility) is within 28 days before the first dose of 
study medication with the exception of the screening disease assessments which may be done 
within 35 days prior to C1D1. Subjects must meet all the inclusion criteria and none of the 
exclusion criteria in Section 4. Retesting of abnormal laboratory values that may lead to exclusion 
will be allowed once. To reassess eligibility, retesting will take place during an unscheduled visit 
in the Screening Phase.
9.1.3.
Treatment Phase
The Treatment Phase will begin with the administration of the first dose of erdafitinib alone or in 
combination with cetrelimab +/- platinum (cisplatin or carboplatin) chemotherapy and will 
continue until disease progression or unacceptable toxicity (based on investigator assessment) 
occurs. Subjects with PD per RECIST 1.1, but for whom the treating physician strongly believes 
that continuation of study treatment is in their best interest, may be allowed to continue on the 
study drug after consultation with the medical monitor (see Section 9.2.2). The subject may receive 
treatment until such time as the treating physician and the medical monitor agree that further 
continuation of treatment is no longer thought to benefit the subject. The subject must follow the 
procedure as outlined in the cohort-specific Time and Events Schedule as if he or she has not 
progressed.
Adverse events occurring any time after the subject signs the Full-Study ICF and up to 100 days 
after the last dose of study drug are to be recorded for all subjects (no AEs will be collected for 
subjects signing the molecular ICF only). Adverse event information will be graded using the 
NCI-CTCAE, version 5.0. See Section 12 for complete details on AE reporting. Concomitant 
medications used will also be recorded throughout this time period.
Throughout the Treatment Phase, the investigator will assess subject response to therapy using the 
RECIST 1.1 criteria (Attachment 9). 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 in the cohort-specific Time and Events Schedule until the start of new anti-cancer 
treatment, disease progression, withdrawal of consent, death, or the end of the study, whichever 
occurs first.

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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 the in the cohort-specific Time and Events 
Schedule. All subjects should have the End-of-Treatment Visit completed within 30 (+7) days after 
the last dose of study drug, and prior to the starting any subsequent cancer treatment, except for 
those who have withdrawn consent, died, or have been lost to follow-up.
Following amendment 5 and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and only SAEs must be reported through the company safety repository.
Additional information on reporting of AEs can be found 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 last dose of study treatment to assess survival status and assess alternate anticancer 
therapy data until death, the subject withdraws consent, or the end of study, whichever occurs first 
as outlined in the cohort-specific Time and Events Schedule. Assessments of survival status and 
alternate anticancer therapies must be recorded in the eCRF. If necessary, this visit can occur by 
telephone. At the first follow-up visit (12 weeks after the last dose), physical examination, vital 
signs, and pregnancy testing should be performed.
Following Amendment 5 and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and subjects in Follow-Up will be considered to have completed the study.
9.2.
Efficacy Evaluations
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 performed during 
the study as indicated in the Time and Events Schedule. The site will send radiographic scans for 
all subjects randomized to Phase 2 to a central vendor for possible future independent assessment 
to confirm the response, if needed.
Computed tomography (CT) scans of the chest, abdomen, pelvis, and any other location where 
disease is present or suspected will be performed at Screening. During the study, disease response 
will be assessed using CT scans of the chest, abdomen, pelvis and any other 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 
Screening 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.
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. Identical methodology (CT scan or magnetic 

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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, and plain X-rays are 
not acceptable methods of evaluating disease response in the absence of CT or MRI scans.
If symptomatic deterioration (based on global deterioration of health status) occurs without 
documentation of radiographic progression, then the clinical findings used to make this 
determination must be specified in the eCRF as “clinical disease progression” and documented in 
the source documents. Every effort should be made to document objective progression via 
radiographic confirmation even after discontinuation of treatment for symptomatic deterioration. 
Tumor response will be reported by the investigator in the eCRF.
Following Amendment 5 and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and only SAEs must be reported through the company safety repository.
9.2.1.
Efficacy Endpoints
Objective response rate according to RECIST 1.1 criteria by investigator assessment is the primary 
endpoint. Duration of response, TTR, PFS, and OS will serve as additional measures of efficacy.
The efficacy endpoints are defined below:

Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or 
PR, as assessed by the investigator.

Duration of Response (DoR) will be calculated from the date of initial documentation of a 
response (CR or PR) to the date of first documented evidence of PD (or relapse for subjects 
who experience CR during the study) or death. Subjects who are progression-free and alive or 
have unknown status will be censored at the last tumor assessment.

Time to Response (TTR) will be calculated from the date of randomization to the date of 
initial documentation of a response (CR or PR).

Progression-free survival (PFS) is defined as the duration from the date of randomization until 
the date of first documented evidence of PD (or relapse for subjects who experience CR during 
the study) or death, whichever comes first. Subjects who are progression-free and alive or 
have unknown status will be censored at the last tumor assessment.

Overall survival (OS) is measured from the date of randomization to the date of the subject’s 
death. If a 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.
9.2.2.
Treatment After Initial Disease Progression
If the site study team makes an initial assessment of disease progression, and if the subject is 
clinically stable, treatment with erdafitinib may be continued. In the case of imaging-based 
progression (RECIST 1.1) subjects may continue to receive study treatment(s) if the investigator 
and sponsor’s clinical team agree and if the subject is clinically stable as defined by the following 
criteria:

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
Absence of signs and symptoms indicating overt disease progression

Stable ECOG PS Grade

Absence of progressive tumor at critical anatomical sites (eg, spinal cord compression, new 
brain metastases) requiring urgent alternative medical intervention
If a subject is approved to continue treatment beyond initial RECIST defined disease progression, 
repeat tumor imaging must be performed at least 4 weeks but no later than 6 weeks after the first 
tumor imaging indicating PD. If repeat imaging meets the threshold for PD (≥20% increase in 
tumor burden [minimum 5 mm] compared to extent of disease at the time of first progression or 
unequivocal new lesion(s), the subject will be discontinued from study treatment.
9.3.
Pharmacokinetics and Immunogenicity
Pharmacokinetic assessments will be performed for erdafitinib, cetrelimab, and platinum (cisplatin 
or carboplatin) chemotherapy cohort. Immunogenicity assessment will be performed for 
cetrelimab.
Following amendment 5, and after end of study data collection timepoint has been achieved, no 
further PK samples of cetrelimab will be collected. An ad-hoc sample for immunogenicity and 
corresponding PK may be collected if required.
Samples for Erdafitinib PK:
Pre-dose and post-dose samples (3 mL per sample) will be collected for erdafitinib as outlined in 
the cohort-specific Time and Events Schedule. Post-dose blood samples should be drawn after 
both the drug infusion and the post-infusion flush have been completed. An additional 4 mL blood 
sample will be collected for determination of the FU (fraction of the unbound erdafitinib) and 
protein levels (total protein, albumin, and alpha-1-acid glycoprotein), as indicated in the cohort-
specific Time and Events Schedule. Blood samples will be processed to obtain plasma for 
measurement of erdafitinib concentration by a validated analytical method under the direction of 
the sponsor. Acid glycoprotein 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. Additional details are provided in the 
Laboratory Manual. The exact date and time of dosing must be recorded on the appropriate eCRF. 
The exact collection date and time of blood sampling must be recorded in the laboratory requisition 
form/source documentation and/or eCRF.
Samples for both cetrelimab PK and anti-cetrelimab antibody determination:
Blood for the assessment of cetrelimab PK and anti-cetrelimab antibody and for immunogenicity 
assessment will be collected as outlined in the cohort-specific Time and Events Schedule.
All pre-infusion samples should be drawn within 30 minutes before infusion of cetrelimab. 
Pharmacokinetic samples are collected from the arm opposite from infusion site. If drug was 
administered via a central venous catheter, sample collection for PK should be from a different 
site. Post-dose blood samples should be drawn after both the drug infusion and the post-infusion 

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. 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. 
Circulating tumor DNA can 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 
 
 
.
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
 
. Adjustments in the 
timing of biomarker collections may be made or collections may be stopped during the study based 
on emerging data.
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.
9.6.
Safety Evaluations
This study will be monitored in accordance with the sponsor’s Pharmacovigilance Committee 
procedures. Adverse event and SAE 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 will review the safety data routinely and will investigate specific safety 
queries. The Safety Management Team will review all SAEs.
Safety assessments will be based on medical review of AE reports and the results of vital sign 
measurements, ECGs, physical examinations, clinical laboratory tests, ECOG PS, and other safety 
evaluations at specified time points as described in the Time and Events Schedules 
(see the cohort-specific Time and Events Schedule).
Following Amendment 5 and after end of study data collection timepoint has been achieved, the 
eCRF will be closed and only SAEs must be reported through the company safety repository.
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 AEs 
such as skin/nail and mucosal toxicity, upon subject consent, photographs may be taken for 
assessment and monitoring of the toxicity.
9.6.1.
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 signing of the Full-Study ICF up to 
CCI
CCI
CCI

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100 days after the last dose of study drug. The incidence of AEs will be tabulated and reviewed 
for potential significance and clinical importance. Adverse events will be graded according the 
NCI-CTCAE, version 5.0. Adverse events will be followed by the investigator as specified in 
Section 12, Adverse Event Reporting.
9.6.2.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected according to the 
cohort-specific 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 AE section of the eCRF. Laboratory test results 
completed on C1D1 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 (locally):
Hematology Panel
-hemoglobin
-platelet count
-white blood cell count and ANC only
Serum Chemistry Panel
-albumin
-magnesium
-sodium
-AST, ALT
-calcium
-total bilirubin
-alkaline phosphatase
-lipase
-potassium
-totalamylase
-creatinine
-HbA1ca
-glucoseb
a If fasting glucose results are available and meet the retreatment criteria, the HbA1c result does not need to be reviewed prior to 
dosing but should still be collected.
b fasting glucose at screening and then only as clinically indicated.
Phosphate (PO4)
Parathyroid hormone (PTH)
Thyroid Panel
-TSH
-T3 (Triiodothyronine)
-FT4 (free thyroxine)
Serology at Screening Only

HIV antibody

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
Hepatitis B virus surface antigen (HBsAg) and core (HBc) antibody: if positive, further testing 
of quantitative levels to rule out active infection is required.

Hepatitis C virus (HCV) antibody: if positive, further testing quantitative levels to rule out 
active infection is required.
9.6.3.
Renal Toxicity Evaluation
Creatinine or creatinine clearance will be determined per institutional standard.
9.6.4.
Urine or Serum Beta-hCG Pregnancy Test
A highly sensitive serum pregnancy test (<5 IU/mL) (-human chorionic gonadotropin [-hCG] 
or urine pregnancy testing should be performed for women of childbearing potential. Additional 
serum or urine pregnancy tests may be performed, as determined necessary by the investigator or 
required by local regulation, to establish the absence of pregnancy at any time during the subject's 
participation in the study. A pregnancy test should also be performed 12 weeks after the last dose 
(see the cohort-specific Time and Events Schedule).
9.6.5.
Electrocardiogram
Screening 12-lead ECGs, to be used to determine subject eligibility, will be performed at the 
study-site. Post-dose ECGs will be collected according to the cohort-specific Time and Events 
Schedule. 
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-minute 
intervals between each assessment. At least 1 printout of all 3 ECG traces 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 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).
9.6.6.
Echocardiography or MUGA Scan
Echocardiograph (ECHO) or multi-gated acquisition scans (MUGA), if ECHO is not available, 
will be performed at Screening to establish baseline cardiac status. Further evaluations may be 
conducted if clinically indicated.
9.6.7.
Ophthalmic Examination
All subjects will have an ophthalmological 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) will 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 

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be performed as clinically necessary based on the findings of the Amsler grid tests and clinical 
assessment, or at regular intervals as deemed necessary by the screening ophthalmologist.
When CSR/Retinal Pigment Epithelial Detachments (RPED) is suspected, or fundoscopic retinal 
abnormalities are observed, as well as each time ocular AEs 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 renal vein occlusion (RVO). In subjects with suspected 
retinal pathology such as CSR or RVO, a consultation with a retina specialist should be considered. 
All images of the OCT scan must be stored in the subject’s records, and a redacted copy sent to 
the sponsor-selected central vendor for possible future independent assessment.
Amsler grid testing will be administered by the treating physician or nurse according to the 
cohort-specific 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 at baseline (during Screening), then a repeat ophthalmic 
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.
9.6.8.
Vital Signs
Blood pressure (systolic and diastolic) and heart rate measurements will be assessed with a 
completely automated device consisting of an inflatable cuff and an oscillatory detection system 
according to the cohort-specific Time and Events Schedules. Temperature and respiratory rate will 
also be assessed. Clinically significant abnormalities should be reported as AEs.
9.6.9.
Physical Examination
A full physical examination will be performed at Screening according to the Time and Events 
Schedule. Limited physical examinations of involved organs will be performed at subsequent visits 
as outlined in the cohort-specific Time and Events Schedule. Clinically significant abnormalities 
should be reported as AEs.
9.6.10.
ECOG Performance Status
ECOG PS Grade will be determined at pre-specified timepoints listed in the cohort-specific Time 
and Events Schedule. ECOG scoring information is provided in Attachment 3.
9.6.11.
Documentation of Hearing Loss
For subjects enrolled in the Phase 2 part of the study, documentation of Grade 2 or higher hearing 
loss is required for cis-ineligible subjects if hearing loss is the single reason for cis-ineligibility. 
Audiometry may be performed, or prior audiometry test results must be available for review. 
In subjects already using hearing aid, documentation of the use of a hearing aid is sufficient for 
this requirement. Audiometry tests that were performed prior to consent for the full-study was 
obtained is permitted to be collected as long as it is documented this procedure was performed as 
part of standard of care and not specifically for study purposes.

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9.7.
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 cohort-specific 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
Following Amendment 5, once the end of study data collection timepoint has been reached, the 
eCRF will be closed and only SAEs must be reported through the company safety repository.
10.1.
Completion
Prior to Protocol Amendment 5, a subject will be considered as having completed the study if he 
or she has died before the end of the study or has not been withdrawn from the study by the end of 
the study (see Section 10.2). Following Amendment 5, once the end of study data collection 
timepoint has been reached, subjects who continue to benefit from study treatment(s), as 
determined by their investigator, may continue to receive access to study treatment(s) on this study, 
with reduced data collection (see Section 17.9.1), either via a long term extension roll-over study 
or any other post-trial access program, when permitted by local regulations.  Provision may 
continue until the subject can commercially access study treatment(s) within the local healthcare 
system, until a decision is made not to pursue the studied indication, until the investigator decides 
it is in the best interest of the subject that study treatment(s) be discontinued, or until 2 years after 
local marketing authorization for is obtained for the studied indication, whichever comes first. 
Once the end of study data collection timepoint has been reached, subjects who have discontinued 
study treatment(s), and all ongoing subjects in the Follow-up Phase will be considered to have 
completed the study (see Section 17.9.1 for definition of end of study data collection).
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
A subject who discontinued treatment will be followed up for recovery of AEs for subsequent 
therapies and survival.
A subject's study treatment must be discontinued if:

The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the 
best interest of the subject to discontinue study treatment

The subject has met any of the criteria listed in Sections 6.2.2 or 6.3.3

The subject becomes pregnant

Disease progression

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
Exception: if the investigator and medical monitor agree that continuation of treatment is in 
the best interest of the subject considering the terminal nature of the underlying disease, he/she 
may receive treatment until such time as the treating physician and the medical monitor agree 
that further continuation of treatment is no longer beneficial to the subject

Unacceptable toxicity

The subject refuses further treatment with the study drug

The sponsor terminates the study

Investigator decision approved by the sponsor
If a subject discontinues study treatment for any reason before the end of the Treatment Phase, an 
End-of-Treatment Visit should be completed, and posttreatment assessments should be obtained 
and scheduled assessments should be continued.
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.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study drug assigned to the withdrawn subject 
may not be assigned to another subject. Subjects may be replaced if 1 of the following criteria is 
met:

The subject withdraws prior to the study drug administration.

The subject is not evaluable for DLT (For the Phase 1b erdafitinib + cetrelimab cohort, refer 
to Section 3.3.1 of Appendix 1. For the Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort, refer to Section 3.3.1 of Appendix 2.)
10.3.
Withdrawal From the Use of Research Samples
The subject may withdraw consent for use of samples for 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.

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11.1.
Sample Size Determination
This is a Phase 1b-2 study comprised of a Phase 1b dose escalation part and a Phase 2 dose 
expansion cohort. The sample size of each phase is calculated as described in Sections 11.1.1 and 
Section 11.1.2.
11.1.1.
Sample Size - Phase 1b
The total number of subjects to be enrolled in Phase 1b will depend on the dose level at which 
DLT of the combination are met or the RP2D is determined. Once a dose level is opened for 
enrollment, subjects will be entered in groups of 3 unless otherwise clinically indicated. A 
minimum of 6 subjects will be treated at a dose level or at the next higher level before the dose 
level can be declared as the RP2D. The expected number of subjects to be enrolled in the Phase 
1b erdafitinib + cetrelimab cohort is 12 to 30.
A total of approximately 40 subjects will be enrolled in the Phase 1b erdafitinib + cetrelimab + 
platinum (cisplatin or carboplatin) chemotherapy cohort. Three subjects (either wild-type or with 
select FGFR gene alterations) will be enrolled in the initial erdafitinib + cetrelimab + cisplatin 
dose level (50 mg/m2). If the starting dose is safe, 6 additional subjects will be enrolled into the 
escalated dose of cisplatin (60 mg/m2). Out of 6 subjects, up to 3 subjects can be wild-type and the 
other subjects should be with select FGFR gene alterations. Wild-type is defined as subjects 
without FGFR gene alteration and subjects with FGFR gene alterations other than the select FGFR 
alterations as described in Table 4. Approximately 10 additional subjects with select FGFR gene 
alterations will be enrolled at the MTD for erdafitinib + cetrelimab + cisplatin.
Three subjects (either wild-type or with select FGFR gene alterations) will be enrolled in the initial 
erdafitinib + cetrelimab + carboplatin dose level (AUC4 mg/mL/min). If the starting dose is safe, 
6 additional subjects will be enrolled into the escalated dose of carboplatin (AUC5 mg/mL/min). 
Out of 6 subjects, up to 3 subjects can be wild-type and the other subjects should be with select 
FGFR gene alterations. Approximately 10 additional subjects with select FGFR gene alterations 
will be enrolled at the MTD for erdafitinib + cetrelimab + carboplatin.
11.1.2.
Sample Size - Phase 2
In Phase 2, approximately 90 subjects will be assigned randomly in a 1:1 ratio to receive either 
erdafitinib monotherapy treatment (Arm A) or erdafitinib and cetrelimab combination therapy 
(Arm B).
1) In the erdafitinib monotherapy arm (Arm A), ORR will be estimated using a 95% 
confidence interval. Assuming a true ORR of 45%, a sample size of approximately 
45 subjects will result in a 95% confidence interval that excludes those less than or equal 
to 30%. 
2) In the erdafitinib and cetrelimab combination therapy (Arm B), ORR will be estimated 
using a 95% confidence interval. Assuming a true ORR of 55%, a sample size of 
approximately 45 subjects result in a 95% confidence interval that excludes ORR less or 
equal to 40%.

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11.2.
Dose Escalation (Phase 1b)
A Modified Toxicity Probability Interval method, mTPI-2, will guide the dose escalation and 
RP2D recommendation in Phase 1b. In the mTPI-2 method, a decision theoretical framework links 
the dose-finding decisions of “Stay”, “De-escalation”, and “Escalation” with the equivalence 
interval ( −,  + ), over-dosing interval(s), and under-dosing interval(s), respectively. In 
this study, we use  = 0.33 and  =  = 0.05, the equivalence interval is (0.28, 0.38). The 
interval, which has the largest posterior probability divided by the length of the interval, is selected 
as the winning interval and the dose-finding recommendation can be set correspondingly. At the 
end of Phase 1b, the estimated MTD is the dose with the smallest difference between the 
transformed posterior mean of  and  and among all the doses d. The detailed dose escalation 
guidelines for this study are outlined in and the SET charter. However, dose selection for the next 
cohort and the decision for RP2D are described in Section 3.3.
11.3.
Analysis Populations
The analysis populations for the Phase 1b dose escalation part of the study are defined as the 
following:

The Treated Population will consist of all subjects who receive at least 1 dose of study drug(s).

DLT Evaluable Population: This set consists of all DLT evaluable subjects (defined in 
Section 3.3.1) among the treated population.
The analysis populations for the Phase 2 dose expansion part of the study are defined as the 
following:

The Treated Population will consist of all subjects who receive at least 1 dose of study drug(s). 
The Treated Population will be used for all safety analyses and for efficacy analysis unless 
otherwise specified in the Statistical Analysis Plan.

The PK/PD Population will consist of all subjects who received at least 1 dose of study dug(s) 
and have at least 1 during treatment sample collected to determine the concentration or PD 
biomarker response.
Subgroup analyses will be performed as appropriate, and details will be specified in the Statistical 
Analysis Plan.
11.4.
Efficacy Analyses (Phase 2 Only)
The primary efficacy analysis is planned with ~6 months of follow-up from last patient enrolled or sooner 
(if last patient discontinued prior to the 6-month follow-up). This will be the final analysis for the study. 
The primary efficacy analysis will be based on the response assessed by investigators. After the end of 
study data collection timepoint has been achieved, no further efficacy data will be collected on the 
eCRF.
To explore the clinical activity of erdafitinib or erdafitinib in combination with cetrelimab in 
Phase 2, the following efficacy analyses will be performed by each arm in the treated population 
according to the RECIST 1.1 criteria:

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
Primary endpoint: ORR will be estimated with a 95% confidence interval. The primary 
efficacy analysis will be based on the response assessed by investigators. 

Secondary endpoints: TTR will be summarized descriptively based on responders. The 
Kaplan-Meier method will be used to estimate the distribution of DoR based on responders. 
The distributions of PFS and OS will be summarized using similar Kaplan-Meier estimates.
11.5.
Pharmacokinetic Analyses
Study drug concentration data will be listed by dose cohort/arm and summarized at each time point 
using descriptive statistics (arithmetic mean, standard deviation [SD], coefficient of variation, 
geometric mean, median, minimum, and maximum). All concentrations below the lowest 
quantifiable concentration or missing data will be labeled as such in the concentration data 
presentation. Concentrations below the lowest quantifiable concentration will be treated as zero in 
the summary statistics and for the calculation of PK parameters. All subjects and samples excluded 
from the analysis will be clearly documented in the study report.
Subjects will be excluded from the PK analysis if their data do not allow for accurate assessment 
of the PK (eg, incomplete administration of the study agent, concentration data not sufficient for 
PK parameter calculation due to missing PK draws at multiple visits, or early discontinuation from 
the study). The data from both phases of the studies will also be analyzed using population PK 
analysis via nonlinear mixed-effect modeling. Previously developed PK models may be used and 
updated as considered appropriate. Data may be combined with data from other studies to support 
a relevant structural population-based PK model. Available subject characteristics (demographics, 
laboratory variables, genotypes, etc.) may be tested as potential covariates affecting PK 
parameters. Individual PK parameters and metrics of exposure for erdafitinib, cetrelimab, and 
carboplatin/cisplatin will be summarized. Details of population PK analyses will be provided in a 
separate analysis plan and results will be described in a separate report, if such analyses are 
performed.
11.6.
Immunogenicity Analyses
The incidence of antibodies to cetrelimab will be summarized for all subjects who receive a dose 
of cetrelimab and have appropriate samples for detection of antibodies to cetrelimab.
11.7.
Pharmacodynamic Analyses, and Biomarker Analyses
 
over time will be summarized by treatment group. Associations 
between baseline levels and changes from baseline in selected markers and clinical response will 
be explored.
Results of exploratory pharmacodynamic biomarker analyses may be presented in a separate 
report. Planned biomarker analyses may be deferred or canceled if emerging data show no 
likelihood of providing useful scientific information.
CCI

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11.8.
Pharmacokinetic/Pharmacodynamic Analyses
Model-derived exposure parameters of erdafitinib, cetrelimab, and platinum chemotherapy may 
be used to explore PK/PD correlation for key efficacy and safety parameters, including the 
influence of covariates, and inter-individual variability between exposure with relevant clinical or 
biomarker information using a population PK/PD approach. Details of these population PK/PD 
analyses will be provided in a separate analysis plan and results may be described in a separate 
report.
11.9.
Safety Analyses
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the most 
current version of the Medical Dictionary for Regulatory Activities (MedDRA). Toxicities will be 
graded for severity according to NCI-CTCAE, version 5.0 (see Table 7 for nail toxicity and 
hyperphosphatemia grading). All reported AEs with onset during the treatment period (ie, TEAEs 
and AEs that have worsened since baseline) will be included in the analysis.
Specifically, the following will be summarized:

Incidence of DLT (Phase 1b)

All AEs, including irAEs

Grade 3 or higher AEs

Serious AEs

AEs leading to permanent discontinuation of treatment

AEs leading to death
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue treatment due to an AE, or who experience a severe AE or an 
SAE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly 
abnormal results (specified in the Statistical Analysis Plan) will be used in the summary of 
laboratory data. Descriptive statistics will be calculated for each laboratory analyte at baseline. 
Parameters with predefined toxicity grades will be summarized. Change from baseline to the worst 
Grade experienced by the subject during the study will be provided as shift tables.
Parameters with predefined NCI-CTCAE toxicity grades will be summarized. Change from 
baseline to the worst AE Grade experienced by the subject during the study will be provided as 
shift tables.

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Vital Signs
Descriptive statistics of pulse/heart rate and blood pressure (systolic and diastolic), and change 
from baseline will be summarized at each scheduled time point. The percentage of subjects with 
values beyond clinically important limits will be summarized.
Physical Examination
Frequency tabulations of the abnormalities will be made.
Electrocardiogram
The effects of erdafitinib and cetrelimab on ECGs (QT, QTc, PR, QRS, heart rate) will be 
evaluated by means of descriptive statistics and frequency tabulations. These tables will include 
observed values and changes from baseline values to allow detection of clinically relevant changes 
in individuals.
11.10. Data Review Committee
A DRC will be established to monitor data on an ongoing basis to ensure the safety of the subjects 
enrolled in Phase 2 of this study. Additionally, the DRC may review ongoing cumulative data from 
Phase 1b after the RP2D has been determined. 
The DRC will consist of at least 2 medical experts in the relevant therapeutic area and at least 
1 statistician. The DRC responsibilities, authorities, and procedures will be documented in a 
separate DRC 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 AEs or SAEs. Open-ended and nonleading 
verbal questioning of the subject is the preferred method to inquire about AE occurrence. For some 
studies, subjects are not always able to provide valid verbal responses to open-ended questions. In 
these circumstances, the investigator will decide the appropriate method of reporting the AE.
Solicited Adverse Events
Solicited AEs are predefined local and systemic events for which the subject is specifically 
questioned.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the subject is specifically not questioned.

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12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 
relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational or non-investigational) product, whether or not related to that medicinal 
(investigational or non-investigational) product. (Definition per International Conference on 
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 AEs starting with the signing of the Full-Study ICF (refer to 
Section 12.3.1, All Adverse Events, for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and European Union (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 1 of the other outcomes listed in the definition above. These should usually 
be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship 
between the study drug and the event (eg, death from anaphylaxis), the event must be reported as 
a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint 
(eg, all-cause mortality).

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Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product 
reference safety information. For erdafitinib and cetrelimab, the expectedness of an AE will be 
determined by whether or not it is listed in the IB.
Adverse Event Associated With the Use of the Drug
An AE 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 AE that is not related to the use of the drug.
Doubtful
An AE 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 AE 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 AE 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 AE 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 AE. The severity 
assessment for an AE or SAE should be completed using the NCI-CTCAE, version 5.0. Any AE 
or SAE not listed in the NCI-CTCAE, version 5.0 will be graded according to the investigator 
clinical judgment by using the standard grades as follows:

Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living.

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
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 AE. 
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 and/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

Any failure of expected pharmacologic action (ie, lack of effect) of a sponsor study drug

Medication error involving a sponsor product (with or without subject exposure to the sponsor 
study drug, eg, name confusion)

Exposure to a sponsor study drug from breast-feeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
For additional details on reporting a retinal abnormality, which is an AE of special interest, see 
Section 6.2.3.6.
12.3.
Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported starting 
from the time a signed and dated Full-Study ICF is obtained until 30 days after the last dose of 
erdafitinib, and 100 days after the last dose of cetrelimab (whichever is longer). If the subject starts 
a subsequent systemic anticancer therapy, AE data collection will be limited to only Grade 2 
immune-related AEs (for subjects who received cetrelimab) and all SAEs from the date the new 
anticancer therapy is initiated until 30 days after the last dose of erdafitinib or 100 days after the 
last dose of cetrelimab, whichever is longer (see table below). Grade 3 and higher AEs, if 
considered related to study drug, occurring more than 100 days after the last dose of study drug 
should also be reported. Resolution information after 100 days should be provided. 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 

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subsequent therapy is started, whichever occurs first. Anticipated events will be recorded and 
reported as described in Attachment 7.
Following Amendment 5, once the end of study data collection timepoint has been achieved, all 
subjects will transition to the schedule of activities in APPENDIX 4. No further data will be 
collected on the eCRF. Subjects who are continuing to derive benefit from study treatment as 
assessed by their investigator may continue to receive study treatment(s); during this period, only 
serious adverse events will be monitored and entered into the Company safety repository.
Study Treatment 
Timing of AE collection
Erdafitinib
All AEs collected until 30 days after the last dose; after this time 
period, Grade 3 and higher AEs related to study treatment*
Cetrelimab
All AEs collected until 100 days after the last dose; after this time 
period, Grade 3 and higher AEs related to study treatment*
Following subsequent systemic anticancer therapy
Erdafitinib
All SAEs collected until 30 days after the last dose
Cetrelimab
Grade ≥2 immune-related AEs and all SAEs collected until 100 
days after the last dose*
*After the end of study data collection date has occurred, only SAEs will be collected and 
entered into the Company safety repository.
All events that meet the definition of a SAE will be reported as SAEs, regardless of whether they 
are protocol-specific assessments. Serious AEs, including those spontaneously reported to the 
investigator within 100 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.
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be 
recorded using medical terminology in the source document and the eCRF. 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 eCRF their opinion concerning the relationship of the 
AE to study therapy. All measures required for AE management must be recorded in the source 
document and reported according to sponsor instructions.
The sponsor assumes responsibility for appropriate reporting of AEs 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 SAEs 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 

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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 SAEs 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.
Information regarding SAEs 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 an SAE should be made by 
facsimile (fax).
All SAEs 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 an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 

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course of a subject's participation in a study must be reported as an SAE, except hospitalizations 
for the following:

A standard procedure for protocol therapy administration will not be reported as an SAE 
including hospitalization due to a longer than anticipated infusion time. Hospitalization or 
prolonged hospitalization for a complication of therapy administration will be reported as an 
SAE.

The administration of blood or platelet transfusion. Hospitalization or prolonged 
hospitalization for a complication of such transfusion remains a reportable SAE.

A procedure for protocol/disease-related investigations (eg, scans, endoscopy, sampling for 
laboratory tests, bone marrow sampling, PK, or biomarker blood sampling). Hospitalization 
or prolonged hospitalization for a complication of such procedures remains a reportable SAE.

Hospitalizations not intended to treat an acute illness or AE (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 eCRF). 
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 SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
12.3.3.
Disease-related Events or Outcomes Not Qualifying as Adverse 
Events or Serious Adverse Events
All events that meet the definition of a SAE will be reported as SAEs, regardless of whether they 
are protocol-specific assessments.
Progression of disease should not be considered nor should be reported as an AE (or SAE). 
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 (refer to Adverse Event Definitions and 
Classifications in Section 12.1.1.).
12.3.4.
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 SAEs and 
must be reported using the Serious Adverse Event Form. Any subject who becomes pregnant 
during the study must discontinue further study treatment. 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 required.

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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.
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 an SAE, the study-site personnel must report the PQC to the sponsor 
according to the SAE 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. It will be manufactured 
and provided under the responsibility of the sponsor. Refer to the erdafitinib IB for a list of 
excipients (Investigator’s Brochure for JNJ-42756493 2018).
Cetrelimab can be supplied as a frozen liquid in vial or a lyophilized product in a vial.
Cetrelimab Frozen Liquid in Vial
The cetrelimab study material supplied for this study is a sterile, frozen liquid. Each vial of 
cetrelimab clinical study material contains 3 mL of a 10 mg/mL cetrelimab solution of cetrelimab. 
It will be manufactured and provided under the responsibility of the sponsor.

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Cetrelimab Lyophilized
Cetrelimab is supplied as a single use, lyophilized product. The 90 mg cetrelimab final lyophilized 
product (FLP) has been designed to deliver 90 mg of a 30 mg/mL solution after reconstitution with 
3 mL of water for injection (WFI). Additionally, a larger vialed 240 mg cetrelimab FLP has been 
designed to deliver 240 mg of a 30 mg/mL solution after reconstitution with 8 mL WFI.
Frozen and lyophilized drug products will be manufactured and provided under the responsibility 
of the sponsor. Refer to the cetrelimab IB for a list of excipients for both the frozen liquid and 
lyophilized drug products (Investigator’s Brochure for JNJ-63723283 2018).
Cisplatin
Cisplatin will be sourced locally by the study-site, subsidiary or designee, depending on local 
country operational or regulatory requirements.
For any commercially available product that is provided by the study-site, subsidiary or designee 
every attempt will be made to source these supplies from a single lot/batch number. The study-site 
will be responsible for recording the lot number, manufacturer and expiry date of any locally 
purchased product.
The investigator shall take responsibility for and shall take all steps to maintain appropriate records 
and ensure appropriate supply, storage, handling, distribution and usage of trial treatments in 
accordance with the protocol and any applicable laws and regulations.
For further information regarding cisplatin refer to the current approved label.
Carboplatin
Carboplatin will be sourced locally by the study-site, subsidiary or designee, depending on local 
country operational or regulatory requirements.
For any commercially available product that is provided by the study-site, subsidiary or designee 
every attempt will be made to source these supplies from a single lot/batch number. The study-site 
will be responsible for recording the lot number, manufacturer and expiry date of any locally 
purchased product.
The investigator shall take responsibility for and shall take all steps to maintain appropriate records 
and ensure appropriate supply, storage, handling, distribution and usage of trial treatments in 
accordance with the protocol and any applicable laws and regulations.
For further information regarding cisplatin refer to the current approved label.
14.2.
Packaging
The study drug will be packaged in kits. The investigational supplies will be uniquely packaged to 
assure that they are appropriately managed throughout the supply chain process.

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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.
Cetrelimab vials will not be dispensed in child-resistant packaging.
Cisplatin and carboplatin will be sourced locally and packaged according to local applicable laws 
and regulations.
No study drugs can be repacked without prior approval of the sponsor.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements.
Cisplatin and carboplatin will be sourced locally and labeled according to local applicable laws and 
regulations.
No study drugs can be relabeled without prior approval of the sponsor.
14.4.
Preparation, Handling, and Storage
All study drugs must be stored as specified on the label.
Refer to the pharmacy manual/study-site investigational product 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. The study drug administered to the subject must be 
documented on the drug accountability form. 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 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 
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 and vials 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 intervention must not be dispensed again, even

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to the same subject. 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:

Study Protocol

Investigator's Brochures

IPPI/SIPPM

Laboratory Manual

RECIST 1.1 guidelines

IWRS Manual

Electronic data capture (eDC) Manual

Sample ICF (Molecular Eligibility and Full-Study)
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Thorough scientific evaluation of any promising treatment before market authorization is an 
ethical requirement. This is the first clinical evaluation of erdafitinib in combination with 
cetrelimab, as well as these study drugs in combination with platinum chemotherapy. As the 
benefits and risks in this study population are not fully known, this study will evaluate the safety 
and clinical activity of these combinations. In this study, 2 dosing schedules (concurrent and 
sequential dosing) may be explored to minimize the potential toxicities. Subjects will be closely 
monitored throughout the study, as discussed throughout this protocol, for both safety and clinical 
benefit. A SET or DRC will review evolving safety data from this study and other relevant studies. 
A discussion about the overall rationale for the study and the anticipated benefits and risks are 
provided in Sections 1.7 and 1.8, respectively. Based on the known data and the mechanism of 
action of both study drugs, there is adequate justification, including significant unmet clinical need, 
for evaluating these drugs in combination for the treatment of urothelial cancer in subjects who 
are eligible for this study.
Additionally, all subjects will undergo periodic disease assessments to monitor the underlying 
disease. The frequency of evaluations is similar to standard practice for patients outside of clinical 
trials and the overall risk is low. Subjects will have pre- and posttreatment tumor biopsies, where 
applicable. In general, these procedures are routinely performed during a subject’s diagnostic 
work-up and follow-up care. Although biopsy collection is associated with risk, the complication 
rate for these procedures is low. The data obtained from this procedure will generate valuable 
scientific data on the pharmacodynamic effect of the combination of these study drugs in this study 
population. As with all clinical and pharmacology studies, there are risks associated with 
venipuncture and multiple blood sample collection. The blood sample collection scheme was 

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designed to collect the minimum number of blood samples that accurately and completely describe 
the pharmacology of the study drug. This minimizes the number of venipunctures and the total 
volume of blood collected from each subject during the study. The volume of blood to be drawn 
is considered to be customary and acceptable for subjects participating in a cancer clinical study 
and is deemed reasonable over the time frame of the study, based upon the standard of the 
American Red Cross (American Red Cross 2015).
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 AEs of the study, and provide their consent voluntarily will be enrolled.
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 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)

IB (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as documented 
by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

Any other documents that the IEC/IRB requests to fulfill its obligation

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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.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
During the study, the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the IB and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs 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.

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16.2.3.
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. 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.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is voluntary 
and that they may withdraw consent to participate at any time. They will be informed that choosing 
not to participate will not affect the care the subject will receive for the treatment of his or her 
disease. Subjects will be told that alternative treatments are available if they refuse to take part and 
that such refusal will not prejudice future treatment. Finally, they will be told that the investigator 
will maintain a subject identification register for the purposes of long-term follow-up if needed 
and that their records may be accessed by health authorities and authorized sponsor personnel 
without violating the confidentiality of the subject, to the extent permitted by the applicable law(s) 
or regulations. By signing the ICF the subject or legally acceptable representative is authorizing 
such access, which includes permission to obtain information about his or her survival status. It 
also denotes that the subject agrees to allow his or her study physician to recontact the subject for 
the purpose of obtaining consent for additional safety evaluations, and subsequent disease-related 
treatments, if needed. The physician may also recontact the subject for the purpose of obtaining 
consent to collect information about his or her survival status.
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.
After informed consent for the study is appropriately obtained, the subject or his or her legally 
acceptable representative will be asked to sign and personally date a separate ICF indicating 
agreement to participate in the optional research component. Refusal to participate in the optional 
research will not result in ineligibility for the study. A copy of this signed ICF will 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.

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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 
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.
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, PK and immunogenicity 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, cetrelimab and 
co-medications in the protocol, and if applicable, to understand cancer, to understand differential 
drug responders, and to develop tests/assays related to erdafitinib, cetrelimab and co-medications 
in the protocol, if applicable. 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 Research Samples).
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help 
ensure access to the developed product if the need for the product persists, unless explicitly 

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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 
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 eCRF 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, 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 

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applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from 
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the vote/opinion 
of the study

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable

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 ICF; 

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dates of visits; results of safety and efficacy parameters as required by the protocol; record of all 
AEs and follow-up of AEs; 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).
The following data will be recorded directly into the eCRF and will be considered source data:

Race

Blood pressure and pulse/heart rate

Height and weight

Details of physical examination

The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries.
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
An 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 an electronic source is utilized, references made to the eCRF 
in the protocol include the electronic source system but information collected through electronic 
source may not be limited to that found in the eCRF. 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 eCRF 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 eCRF are accurate and 
correct.

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The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, 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 eCRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
eCRF in English. The eCRF 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.
If necessary, queries will be generated in the eDC tool. If corrections to a eCRF are needed after 
the initial entry into the eCRF, 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 
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 eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review the eCRF 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 eCRF 
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.

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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 eCRF 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 
eCRF 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.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these 
remote contacts, study-site personnel will be available to provide an update on the progress of the 
study at the site.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The end of the study is defined as the last study assessment for the last subject on study or anytime 
the sponsor terminates the study, whichever comes first. 
Prior to Protocol Amendment 5, the final data from the study-site was to be sent to the sponsor (or 
designee) after completion of the final subject visit at that study-site, in the time frame specified 
in the clinical trial agreement.

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Following Amendment 5, the end of study data collection is defined as when the primary efficacy 
analysis clinical cutoff has been achieved. At that time, follow up of subjects will end and the eCRF 
will be closed. Subjects who are continuing to derive benefit from erdafitinib and/or cetrelimab 
treatment as assessed by their investigator may continue to receive erdafitinib and/or cetrelimab; during 
this period, only serious adverse events will be monitored and entered into the Company safety 
repository.
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. 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.
The sponsor will ensure that subjects benefiting from study treatment(s) can continue to receive 
treatment(s) after the study has been terminated.
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.

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17.11. Use of Information and Publication
All information, including but not limited to information regarding erdafitinib, cetrelimab, 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 cetrelimab, 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 biomarker analyses 
performed after the Clinical Study Report has been issued will be reported in a separate report and 
will not require a revision of the Clinical Study Report. Study subject identifiers will not be used 
in publication of results. Any work created in connection with performance of the study and 
contained in the data that can benefit from copyright protection (except any publication by the 
investigator as provided for below) shall be the property of the sponsor as author and owner of 
copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors 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 18 months after study end date, or the sponsor confirms there 
will be no multicenter study publication. Authorship of publications resulting from this study will 

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be based on the guidelines on authorship, such as those described in the ICMJE Recommendations 
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design 
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the 
work or revised it critically for important intellectual content; and given final approval of the 
version to be published; and agreed to be accountable for all aspects of the work in ensuring that 
questions related to the accuracy or integrity of any part of the work are appropriately investigated 
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required 
by law.

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Attachment 4:
Drugs Classified as Strong CYP3A4 Inhibitors, Moderate to Strong CYP3A4 
Inducers, Moderate CYP2C9 Inhibitors, and Moderate CYP2C9 Inducers
Strong CYP3A4 Inhibitors
Boceprevir
Conivaptan
Clarithromycin
Indinavir
Grapefruit juice
Itraconazole
Lopinavir
Ketoconazole
Mibefradil
Ritonavir
Nefazodone
Nelfinavir
Posaconazole
Conivaptan
Saquinavir
Boceprevir
Telaprevir
Clarithromycin
Telithromycin
Erythromycin
Voriconazole
Troleandomycin
Fluconazole
Strong Inhibitors: ≥5-fold increase in AUC or >80% decrease in CL.
Moderate to Strong CYP3A4 Inducers
Moderate CYP3A4 Inducers
Bosentan
Efavirenz
Etravirine
Modafinil
Nafcillin
Lersivirine
Talviraline
Tipranavir
Lopinavir
Strong CYP3A Inducers
Avasimibe
Carbamazepine
Barbiturates eg, phenobarbital
Phenytoin
Rifabutin
Rifampin
St. John’s wort
Mitotane
Enzalutamide
Apalutamide
Strong Inducers: ≥80% decrease in area under the curve (AUC). Moderate Inducers: 50% to 80% decrease in AUC.
Moderate CYP2C9 Inhibitors
Fluconazole
amiodarone
Miconazole
piperine
Oxandrolone
atacigual
tienilic acid
azapropazone
Bucolome
sulfaphenazole
Benzbromarone
Moderate CYP2C9 Inducers
Carbamazepine
rifampin
Enzalutamide
aprepitant
Reference: University of Washington’s Drug Interaction Database
http://www fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664 h
tm#4
Both these references may not be exhaustive and up-to-date at any given time. Please consult the product information of ongoing 
and new concomitant medications for the most accurate information on potential moderate to strong inhibitors or inducers of 
CYP3A4 and CYP2C9.

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Attachment 5: Amsler Grid

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Attachment 6:
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 7: Anticipated Events
Anticipated Event
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence of 
the underlying disease or condition under investigation (disease-related) or background regimen.
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

Urine flow decreased

Urinary retention

Urinary tract obstruction

Urinary tract stoma complication

Urinary tract pain

Urinary tract infection

Urosepsis
Because this is the first study of the combination of cetrelimab and erdafitinib, other AEs cannot 
be anticipated. Platinum-based chemotherapies, cisplatin and carboplatin, are known to have 
similar but varying frequency of AEs such as thrombocytopenia, leukopenia, anemia, vomiting, 
nausea, nephrotoxicity, neurotoxicity and ototoxicity, when used as monotherapies, and increase 
in severity or frequency of such AEs in the cisplatin and carboplatin combination cohorts in this 
study cannot be anticipated.
Reporting of Anticipated Events
All AEs will be recorded in the electronic case report form (eCRF), regardless of whether 
considered to be anticipated events and will be reported to the sponsor as described in 
Section 12.3.1. Any anticipated event that meets serious criteria will be reported to the sponsor as 
described in Section 12.3.2. Each anticipated event will be assessed by the investigator at the 
individual case level and if considered to be drug-related will undergo expedited reporting (if 
appropriate) per applicable clinical trial legislation to Health Authorities and IRB/ECs (Note: 
Japan will not identify anticipated events for the health authorities). If an anticipated event is 

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considered disease-related or not related to study drug the event will be exempt from expedited 
reporting.
To meet US regulatory clinical trial legislation, the sponsor will perform aggregate review of 
anticipated events as outlined below, and if determined to be drug-related will implement 
expedited reporting of these events to Health Authorities and IRBs/ECs. If an interim analysis of 
trial results leads to an unblinded, aggregate review of safety data by the study team, the sponsor 
may terminate the review of pre-specified anticipated events outlined above.
Safety Assessment Committee (SAC)
A SAC will be established to perform reviews of pre-specified anticipated events at an aggregate 
level. The SAC is a safety committee within the sponsor’s organization that is independent of the 
sponsor’s study team. 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 based on a review of the aggregate data by arm.
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.

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Attachment 8: Cockcroft-Gault Formula for Estimated Creatinine Clearance (CrCl)
eCR= (140-Age) x Mass (kilograms) x [0.85 if female]
72 x Serum Creatinine (in mg/dL1)
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
http:www.mdcal.com/creatinine-clearance-cockcroft-gault-equation/

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Attachment 9: RECIST GUIDELINES
Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
The following information was extracted from Section 3, Section 4, and Appendix I of the New response evaluation 
criteria in solid tumours: revised RECIST guideline (version 1.1) authored by Eisenhauer et al (2009). Refer to the 
European Journal of Cancer article (2009;45(2):228-247) for the complete publication.
Measurability of tumor at baseline
Definitions
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as follows:
Measurable:
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement 
is to be recorded) with a minimum size of:

10 mm by CT scan (CT scan slice thickness no greater than 5 mm)

10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should 
be recorded as non-measurable)

20 mm by chest X-ray

Lymph nodes to be considered pathologically enlarged and measurable. A lymph node must be ≥15 mm 
in the short axis when assessed by CT scan (CT scan slice thickness is recommended to be a maximum 
of 5 mm). At baseline and follow-up, only the short axis will be measured and followed.
Non-measurable:
All other lesions, including small lesions (longest diameter <10 mm or pathological lymph nodes with 10 to <15 mm 
short axis) as well as truly non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, 
abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible 
imaging techniques.
Specifications by methods of measurements
The same method of assessment and the same technique should be used to characterize each identified and reported 
lesion at baseline and during follow-up. Imaging-based evaluation should always be done rather than clinical 
examination unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam.
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial and 10 mm diameter 
as assessed using calipers (e.g. skin nodules). For the case of skin lesions, documentation by color photography 
including a ruler to estimate the size of the lesion is suggested. As noted above, when lesions can be evaluated by both 
clinical exam and imaging, imaging evaluation should be undertaken since it is more objective and may also be 
reviewed at the end of the study.
Chest X-ray: Chest CT is preferred over chest X-ray, particularly when progression is an important endpoint, since 
CT is more sensitive than X-ray, particularly in identifying new lesions. However, lesions on chest X-ray may be 
considered measurable if they are clearly defined and surrounded by aerated lung. See Appendix II for more details.
CT, MRI: CT is the best currently available and reproducible method to measure lesions selected for response 
assessment. This guideline has defined measurability of lesions on CT scan based on the assumption that CT slice 
thickness is 5 mm or less. As is described in Appendix II, when CT scans have slice thickness greater than 5 mm, the 
minimum size for a measurable lesion should be twice the slice thickness. MRI is also acceptable in certain situations 
(e.g. for body scans). More details concerning the use of both CT and MRI for assessment of objective tumor response 
evaluation are provided in Appendix II.

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Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a method of measurement. 
Ultrasound examinations cannot be reproduced in their entirety for independent review at a later date and, because 
they are operator dependent, it cannot be guaranteed that the same technique and measurements will be taken from 
one assessment to the next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT 
or MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of CT in selected 
instances.
Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation is not advised. However, 
they can be useful to confirm complete pathological response when biopsies are obtained or to determine relapse in 
trials where recurrence following complete response or surgical resection is an endpoint.
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. If markers are initially above 
the upper normal limit, however, they must normalize for a patient to be considered in complete response (CR).
Cytology, histology: These techniques can be used to differentiate between PR and CR in rare cases if required by 
protocol (for example, residual lesions in tumor types such as germ cell tumors, where known residual benign tumors 
can remain). When effusions are known to be a potential adverse effect of treatment (e.g. with certain taxane 
compounds or angiogenesis inhibitors), the cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment can be considered if the measurable tumor has met criteria for response or stable 
disease in order to differentiate between response (or stable disease) and progressive disease.
Tumor response evaluation
Assessment of overall tumor burden and measurable disease
To assess objective response or future progression, it is necessary to estimate the overall tumor burden at baseline
and use this as a comparator for subsequent measurements. Measurable disease is defined by the presence of at least 
one measurable lesion
Baseline documentation of ‘target’ and ‘non-target’ lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of five lesions total (and a 
maximum of two lesions per organ) representative of all involved organs should be identified as target lesions and 
will be recorded and measured at baseline.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be representative of all 
involved organs, but in addition should be those that lend themselves to reproducible repeated measurements. It may 
be the case that, on occasion, the largest lesion does not lend itself to reproducible measurement in which circumstance 
the next largest lesion, which can be measured reproducibly, should be selected.
A sum of the diameters (longest for non-nodal lesions,) for all target lesions will be calculated and reported as the 
baseline sum diameters. The baseline sum diameters will be used as reference to further characterize any objective 
tumor regression in the measurable dimension of the disease.
All other lesions (or sites of disease) should be identified as non-target lesions and should also be recorded at baseline. 
Measurements are not required and these lesions should be followed as ‘present’, ‘absent’, or in rare cases 
‘unequivocal progression. In addition, it is possible to record multiple non-target lesions involving the same organ as 
a single item on the case record form (e.g. ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’).
Response criteria
This section provides the definitions of the criteria used to determine objective tumour response for target lesions.
Evaluation of target lesions
Complete Response (CR): Disappearance of all target lesions.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the 
baseline sum diameters.

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Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest 
sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new 
lesions is also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive 
disease, taking as reference the smallest sum diameters while on study.
Evaluation of non-target lesions
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level.
Non-CR/Non-progressive disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits.
Progressive Disease: Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more 
new lesions is also considered progression).
Evaluation of best overall response
The best overall response is the best response recorded from the start of the study treatment until the end-of-treatment 
taking into account any requirement for confirmation. On occasion a response may not be documented until after the 
end of therapy so protocols should be clear if posttreatment assessments are to be considered in determination of best 
overall response. The patient’s best overall response assignment will depend on the findings of both target and non-
target disease and will also take into consideration the appearance of new lesions.
Timepoint response
It is assumed that at each protocol-specified timepoint, a response assessment occurs. Table 1 on the next page 
provides a summary of the overall response status calculation at each timepoint for patients who have measurable 
disease at baseline.
When patients have non-measurable (therefore non-target) disease only, Table 2 is to be used.
Best overall response: all timepoints
The best overall response is determined once all the data for the patient is known.
Best response determination in trials where confirmation of complete or partial response IS NOT required: Best 
response in these trials is defined as the best response across all timepoints (for example, a patient who has SD at first 
assessment, PR at second assessment, and progressive disease on last assessment has a best overall response of PR). 
When SD is believed to be best response, it must also meet the protocol-specified minimum time from baseline. If the 
minimum time is not met when SD is otherwise the best timepoint response, the patient’s best response depends on 
the subsequent assessments. For example, a patient who has SD at first assessment, progressive disease at second and 
does not meet minimum duration for SD, will have a best response of progressive disease. The same patient lost to 
follow-up after the first SD assessment would be considered inevaluable.
Table 1 - Timepoint Response: Patients with Target (+/- Non-target) Disease
Target lesions
Non-target lesions
New lesions
Overall response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease; NE = inevaluable.

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Table 2 - Timepoint Response: Patients with Non-Target Disease Only
Non-target lesions
New lesions
Overall response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response; PD = progressive disease; NE = inevaluable.
a Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence 
of disease progression at that time should be reported as ‘symptomatic deterioration’. Every effort should be made to 
document objective progression even after discontinuation of treatment. Symptomatic deterioration is not a descriptor 
of an objective response: it is a reason for stopping study therapy. The objective response status of such patients is to 
be determined by evaluation of target and non-target disease as shown in Tables 1–2.
Conditions that define ‘early progression, early death and inevaluability’ are study-specific and should be clearly 
described in each protocol (depending on treatment duration, treatment periodicity).
In some circumstances it may be difficult to distinguish residual disease from normal tissue. When the evaluation of 
complete response depends upon this determination, it is recommended that the residual lesion be investigated (fine 
needle aspirate/biopsy) before assigning a status of complete response. FDG-PET may be used to upgrade a response 
to a CR in a manner similar to a biopsy in cases where a residual radiographic abnormality is thought to represent 
fibrosis or scarring. The use of FDG-PET in this circumstance should be prospectively described in the protocol and 
supported by disease specific medical literature for the indication. However, it must be acknowledged that both 
approaches may lead to false positive CR due to limitations of FDG-PET and biopsy resolution/ sensitivity.
For equivocal findings of progression (e.g. very small and uncertain new lesions; cystic changes or necrosis in existing 
lesions), treatment may continue until the next scheduled assessment. If at the next scheduled assessment, progression 
is confirmed, the date of progression should be the earlier date when progression was suspected.
Duration of overall response
The duration of overall response is measured from the time measurement criteria are first met for CR/PR (whichever 
is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference 
for progressive disease the smallest measurements recorded on study).
The duration of overall complete response is measured from the time measurement criteria are first met for CR until 
the first date that recurrent disease is objectively documented.
Duration of stable disease
Stable disease is measured from the start of the treatment (in randomised trials, from date of randomisation) until the 
criteria for progression are met, taking as reference the smallest sum on study (if the baseline sum is the smallest, this 
is the reference for calculation of progressive disease).
The clinical relevance of the duration of stable disease varies in different studies and diseases. If the proportion of 
patients achieving stable disease for a minimum period of time is an endpoint of importance in a particular trial, the 
protocol should specify the minimal time interval required between two measurements for determination of stable 
disease.

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Attachment 10:
Guidance on Study Conduct During a National Disaster for Enrolled Subjects 
It is recognized that a national disaster, eg, pandemic, may have an impact on the conduct of this 
clinical study. In alignment with the recent health authority guidances, the sponsor is providing 
guidance for study-related patient management in the event of disruption to the per protocol 
conduct of the study as outlined throughout the protocol. These measures are to be followed on a 
temporary basis. Once the national situation allows, the usual study conduct methods will resume. 
This guidance does not supersede any local or government requirements or the clinical judgment 
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 judgment, 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 eCRF. 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.

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
Critical laboratory tests, imaging or other diagnostic tests may be done at an 
authorized/certified (as legally required nationally) local laboratory or clinical facility. A 
copy of the laboratory report must be reviewed by the investigator and retained, along with 
the reference ranges, for the source documentation and provided with the eCRF.

Consenting of subjects for full-study screening will be performed as applicable (including 
also remote consenting by telephone or video consultation) according to local guidance for 
the informed consent. (Remote consenting for molecular eligibility screening is described 
in the main body of the protocol.)

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APPENDIX 1:
PHASE 1B ERDAFITINIB + CETRELIMAB
1.
INTRODUCTION.............................................................................................................................. 174
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS......................................................................... 174
2.1.
Objectives and Endpoints for Phase 1b (Dose Escalation) ......................................................... 174
2.2.
Hypothesis for Phase 1b (Dose Escalation) ................................................................................ 174
3.
STUDY DESIGN AND RATIONALE ............................................................................................... 174
3.1.
Overview of Study Design............................................................................................................ 174
3.1.1.
Phase 1b for Erdafitinib + Cetrelimab Cohort........................................................................... 175
3.2.
Study Design and Starting Dose Rationale.................................................................................. 176
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D................................................... 176
3.3.1.
Definition of Dose-Limiting Toxicity for Phase 1b (Dose Escalation) ....................................... 177
3.3.2.
Determination of the Phase 1b RP2D Regimen and Alternative Dosing Schedules ............... 178
3.4.
Study Evaluation Team................................................................................................................ 178
4.
SUBJECT POPULATION................................................................................................................ 178
4.1.
Inclusion Criteria .......................................................................................................................... 179
4.2.
Exclusion Criteria ......................................................................................................................... 184
5.
TREATMENT ALLOCATION AND BLINDING............................................................................... 187
6.
DOSAGE AND ADMINISTRATION ................................................................................................ 187
6.1.
Dose Combination for Erdafitinib + Cetrelimab Cohort................................................................ 187

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3.1.1.
Phase 1b for Erdafitinib + Cetrelimab Cohort
The Phase 1b erdafitinib + cetrelimab cohort represent the dose escalation part of the study. A
Modified Toxicity Probability Interval method, mTPI-2, (Guo 2017) will be used by the Study 
Evaluation Team (SET, Section 3.4) to guide the dose escalation and RP2D(s) regimen 
recommendations (see Section 11.2, Attachment 1 and the SET charter). The expected number of 
subjects to be treated in the Phase 1b erdafitinib + cetrelimab cohort will range from 12 to 30.
Two dosing regimens may be explored: Standard Dose Levels (DL1, DL2 or DL2A) or Alternative 
Dose Levels (DL1B or DL2B) (Figure 1). Two dosing cohorts of erdafitinib may be explored, 
while cetrelimab IV dose will be fixed.

Erdafitinib + cetrelimab Standard Dose Levels (DL1, DL2 or DL2A)
In the Standard Dose Levels, erdafitinib and cetrelimab starts concurrently from C1D1. The DLT 
evaluation period is 1 cycle (4 weeks [28 days]).
or

Erdafitinib + cetrelimab Alternative Dose Levels (DL1B or DL2B)
In the Alternative Dose Levels, administration of erdafitinib starts on C1D1 but cetrelimab is 
initiated 1 cycle (28 days) later, on C2D1. A DLT period is 2 cycles (8 weeks). It is hypothesized 
that an initial erdafitinib monotherapy for 4 weeks may lead to improved tolerance of the 
subsequent concurrent dosing with a checkpoint inhibitor. The Alternative Dose Levels at the same 
dose is considered one dose level down from the Standard Cohort: DL1B for DL1 and DL2B for 
DL2/DL2A.
For the Phase 1b erdafitinib + cetrelimab cohort, cetrelimab will be dosed at 240 mg Q2W for 
Cycles 1 through 4 and 480 mg Q4W starting at Cycle 5. Refer to Figure 1 for an overview of the 
Phase 1b: erdafitinib + cetrelimab cohort.
The starting dose is DL1 (6 mg erdafitinib + 240 mg cetrelimab).
If based on the below rules, de-escalation is indicated from DL1, the one dose level down (DL1B) 
is started, and the Standard Dose Levels are abandoned. DL1B is the lowest dose cohort to be 
tested.
If based on the below rules, escalation is indicated from DL1, then DL2 and DL2A are started 
(with subjects being assigned to either cohort based on the pharmacodynamic up-titration rules).
If based on the below rules, de-escalation is indicated from DL2/DL2A, then DL2B is started.
The following rules for escalation/de-escalation apply throughout the Phase 1b part of the study:

At least 3 subjects may be dosed in each dose level that will be explored.

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
A staggered enrollment strategy will be applied to the first 3 subjects in a dose level. A 
minimal interval of 24 hours between a subject's first dose will be required.

At least 3 subjects per dose level are required to complete the DLT evaluation period (1 cycle 
for the Standard Dose Levels and 2 cycles for the Alternative Dose Levels) or be discontinued 
for DLT before the SET can determine the dose and schedule for the next dose level.

The SET will evaluate all available data including, but not limited to, PK, PD, safety, and 
preliminary anti-tumor activity, and will decide whether to escalate, stay at the current dose, 
or de-escalate the dose level based on the mTPI-2 guidelines outlined in Attachment 1. These 
are briefly explained for the case with 3 subjects treated at a dose level:

If no subject in a dose level experiences a DLT, dose escalation may proceed as guided by 
mTPI-2. The SET will confirm the dose level chosen for the next dose cohort.

If 1 out of 3 subjects in a dose level experiences DLT during the DLT evaluation period, then the 
SET may decide to enroll additional subjects before determining the next dose level

If 2 out of 3 subjects in a dose level experience DLT during the DLT evaluation period, dose 
de-escalation may proceed as guided by mTPI-2. The SET will confirm the dose level chosen for 
the next dose cohort.

If 3 out of 3 subjects in a dose level experience DLT during the DLT evaluation period, dose 
de-escalation may proceed as guided by mTPI-2 and no further subjects will be dosed at this dose 
cohort in the study. The SET will confirm the dose level chosen for the next dose cohort.

Dose escalation guided by the SET may continue until the RP2D is identified.
The identification of the RP2D will be based on the totality of data from all dose cohorts tested. 
Note: 8 mg with or without up-titration (DL2 and DL2A) may be considered as the same dose 
level.

The SET can evaluate up-titrated and non-up-titrated subjects separately or combined based 
on the totality of the emerging safety data. The SET will also determine whether to modify or 
terminate dose cohorts, include additional dose cohorts, change doses or schedules of either 
drug, modify the study conduct if deemed necessary, and select the RP2D regimen for Phase 
2 based on the emerging data (see Section 3.4).

Intra-subject dose escalation is not allowed and subjects in Phase 1b will not be entered into 
Phase 2.
3.2.
Study Design and Starting Dose Rationale
Refer to Section 3.2 of the main body of the protocol.
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D
During Phase 1b, subjects will be entered in group at each dose level based on the mTPI-2 method 
(Guo 2017). After the last subject in each group (minimum of 3 DLT evaluable subjects) has 
completed the DLT observation period or developed a DLT, the SET will evaluate all available 
safety data and make the decision whether to escalate, stay at the current dose or de-escalate the 

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investigator should consult with the appropriate sponsor representative before enrolling a subject 
in the study. For a discussion of the statistical considerations of subject selection, refer to 
Section 11.1, 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.
2.
Criterion modified per Amendment 2
2.1 Histologic demonstration of transitional cell carcinoma of the urothelium. Variant 
urothelial carcinoma histologies such as glandular or squamous differentiation, or 
evolution to more aggressive phenotypes such as sarcomatoid or micropapillary 
change are acceptable.
3.
Criterion modified per Amendment 2
3.1 Metastatic or locally advanced urothelial cancer (Stage IV disease per AJCC Staging 
Guidelines)
4.
Criterion modified per Amendment 2
4.1 Criterion modified per Amendment 3
4.2 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Meet appropriate molecular 
eligibility criteria. Tumors must have at least one gene fusion or gene mutation as 
defined in Table 4.
Exception for Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: up to 3 subjects in each 
erdafitinib + cetrelimab + chemotherapy cohort at each dose level will be wild-type. Wild-type is defined 
as subjects without FGFR gene alteration and subjects with FGFR gene alterations other than the select 
FGFR alterations described in Table 4. All other subjects must have at least one select FGFR alteration 
as defined in Table 4.
5.
Criterion modified per Amendment 2
5.1 Must have measurable disease by radiological imaging according to the Response 
Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline.
6.
Criterion modified per Amendment 2
6.1 Criterion modified per Amendment 3

6.2 Prior systemic therapy for metastatic urothelial cancer:

Phase 1b erdafitinib + cetrelimab cohort:

Any number of lines of prior therapy

Renal function for subjects must have a creatinine clearance (CrCl) ≥30 mL/min 
as calculated by Cockcroft-Gault (Attachment 8)

Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:

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9.1 Criterion modified per Amendment 1.
9.2 Criterion modified per Amendment 3
9.3 Phase 1b erdafitinib + cetrelimab cohort and Phase 2:
Before the first dose of study drug:
Women of childbearing potential (defined as: fertile, following menarche and until 
becoming post-menopausal unless permanently sterile as a result of hysterectomy, 
bilateral salpingectomy, or bilateral oophorectomy) and fertile men who are sexually 
active must agree to use a highly effective method of contraception (<1%/year failure 
rate) during the study and for 5 months after the last dose of study drug. For men who 
are sexually active with women of childbearing potential: agree to use a condom with 
spermicidal foam/gel/film/cream/suppository during the study and for 5 months after 
the last dose of study drug. Contraception must be consistent with local regulations 
regarding the use of birth control methods for subjects participating in clinical trials. 
Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, 
during the study and for 5 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception 
associated with inhibition of ovulation; intrauterine device; intrauterine hormone-
releasing system; vasectomized partner;
–
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.
Note: If the childbearing potential changes after start of the study or the risk of 
pregnancy changes, a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria. If reproductive status is questionable, 
additional evaluation should be considered. It should be noted that interaction between 
hormonal contraception and the combination of the study drugs have not been studied. 
Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of true sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, post-

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ovulation methods], declaration of abstinence for the duration of exposure to the study 
drugs, and withdrawal are not acceptable methods of contraception).
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
Before the first dose of study drug:
Women of childbearing potential (defined as: fertile, following menarche and until becoming post-
menopausal unless permanently sterile as a result of hysterectomy, bilateral salpingectomy, or bilateral 
oophorectomy) and fertile men who are sexually active must agree to use a highly effective method of 
contraception (<1%/year failure rate) during the study and for 6 months after the last dose of study drug. 
For men who are sexually active with women of childbearing potential: agree to use a condom with 
spermicidal foam/gel/film/cream/suppository during the study and for 6 months after the last dose of 
study drug. Contraception must be consistent with local regulations regarding the use of birth control 
methods for subjects participating in clinical trials. Women and men must agree not to donate eggs (ova, 
oocytes) or sperm, respectively, during the study and for 6 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception associated with 
inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized 
partner;
–
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.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes, a 
woman must begin a highly effective method of contraception, as described throughout the inclusion 
criteria. If reproductive status is questionable, additional evaluation should be considered. It should be 
noted that interaction between hormonal contraception and the combination of the study drugs have not 
been studied. Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of true sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, 
post-ovulation methods], declaration of abstinence for the duration of exposure to the study drugs, and 
withdrawal are not acceptable methods of contraception).
10.
Women of childbearing potential must have a negative pregnancy test at Screening 
within ≤7 days of C1D1 (first dose of study drug) using a highly sensitive pregnancy 
test (serum -human chorionic gonadotropin [-hCG]); see Section 9.6.4).
11.
Sign an informed consent form indicating that he or she understands the purpose of and 
procedures required for the study, and is willing and able to participate in the study. 
Consent is to be obtained prior to the initiation of any study-related tests or procedures 
that are not part of standard of care for the subject’s disease.
12.
Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

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4.2.
Exclusion Criteria
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 C1D1. For Phase 1b, subjects who have 
received the following prior anti-tumor therapy:

Received nitrosoureas and mitomycin C within 6 weeks. 
2.
Criterion modified per Amendment 3
2.1 Phase 1b erdafitinib + cetrelimab cohort:

Chemotherapy within 3 weeks of C1D1.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2:

Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to 
recurrent disease progression and did not result in drug-related toxicity leading to treatment 
discontinuation.
3.
Criterion modified per Amendment 2
3.1 Criterion modified per Amendment 3
3.2 Prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. Prior neoadjuvant/adjuvant 
checkpoint inhibitor therapy is allowed if the last dose was given >12 months prior to 
recurrent disease progression and did not result in drug-related toxicity leading to 
treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also 
allowed.
4.
Criterion modified per Amendment 2
4.1 Active malignancies requiring concurrent therapy other than urothelial cancer.
5.
Symptomatic central nervous system metastases.
6.
Prior FGFR inhibitor treatment.
7.
Radiation therapy ≤30 days prior to planned C1D1. 
8.
Criterion modified per Amendment 2
8.1 Criterion modified per Amendment 3
8.2 History of uncontrolled cardiovascular disease including:

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
Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de 
Pointes, cardiac arrest, or known congestive heart failure Class III-V (Attachment 
6) within the preceding 3 months; cerebrovascular accident or transient ischemic 
attack within the preceding 3 months.
9.
Known to be seropositive for human immunodeficiency virus or acquired immune 
deficiency syndrome.
10.
Any of the following:

Evidence of serious active viral, bacterial, or uncontrolled systemic fungal 
infection.

Active autoimmune disease or a documented history of autoimmune disease that 
requires systemic steroids or immunosuppressive agents.
Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception 
to this rule. Subjects that require intermittent use of bronchodilators or local steroid 
injections would not be excluded from the study. Subjects with hypothyroidism stable 
on hormone replacement will not be excluded from the study. Subjects with a history 
of transient autoimmune manifestations of an acute infectious disease that resolved 
upon treatment of the infectious agent (eg, acute Lyme arthritis) will not be excluded 
from the study.

Grade 3 or higher toxicity effects from previous treatment with immunotherapy.

Psychiatric conditions (eg, alcohol or drug abuse), dementia, or altered mental 
status.

Any other issue that would impair the ability of the subject to receive or tolerate 
the planned treatment at the investigational site, to understand informed consent or 
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.
11.
Pulmonary compromise requiring supplemental oxygen use to maintain adequate 
oxygenation.
12.
Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface 
antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) 
positivity at Screening. If positive, further testing of quantitative levels to rule out 
active infection is required (see Attachment 2).

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13.
Criterion modified per Amendment 3
13.1
Phase 1b erdafitinib + cetrelimab and Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort: Not recovered from reversible toxicity of prior anticancer therapy 
(except toxicities which are considered by the investigator as not clinically significant, 
such as alopecia, skin discoloration, or Grade 1 hearing loss or neuropathy).
Phase 2: Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are 
considered by the investigator as not clinically significant such as alopecia, or skin discoloration).
14.
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, 
known gastric ulcers, or unhealed incisions.
15.
Criterion modified per Amendment 2
15.1 Allergies, hypersensitivity, or intolerance to protein-based therapies or with a 
history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or 
immune-mediated thrombocytopenia or anemia), or to excipients of erdafitinib or 
cetrelimab (see the Investigator’s Brochures for a list of excipients).
16.
Criterion modified per Amendment 2
16.1 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment 
(RPED) of any Grade.
17.
Criterion deleted per Amendment 2
18.
Criterion modified per Amendment 2
18.1 Use of immunosuppressant agents, including, but not limited to: systemic 
corticosteroids at doses exceeding 10 mg/day of prednisone or its equivalent, 
methotrexate, cyclosporine, azathioprine, and tumor necrosis factor α (TNF-α) 
blockers, within 2 weeks before the planned first dose of study drug.
19.
Vaccinated with a live attenuated vaccine within 28 days prior to the first dose of study 
drug and for 3 months after receiving the last dose of study drug. Annual inactivated 
influenza vaccine is permitted.
20.
Criterion modified per Amendment 3
20.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Pregnant or breast-feeding, 
or planning to become pregnant while enrolled in this study or within 5 months after 
receiving the last dose of study drug.

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Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Pregnant or breast-feeding, or 
planning to become pregnant while enrolled in this study or within 6 months after receiving the last dose 
of study drug.
21.
Criterion modified per Amendment 3
21.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Plans to father a child 
while enrolled in this study or within 5 months after receiving the last dose of study 
drug.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Plans to father a child while enrolled 
in this study or within 6 months after receiving the last dose of study drug.
22.
Criterion modified per Amendment 2
22.1 Major surgery within 4 weeks of enrollment, or inadequate recovery from the 
toxicity and/or complications from the intervention prior to starting therapy. 
23.
Criterion modified per Amendment 3
23.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: not applicable.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: known sensitivity to any component 
of cisplatin or carboplatin.
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 the 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
This is an open-label study. No blinding procedures will be applied.
6.
DOSAGE AND ADMINISTRATION
Phase 1b erdafitinib + cetrelimab cohort: On days that both drugs will be administered, the 
sequence of administration will be oral erdafitinib followed by the infusion of cetrelimab IV.
6.1.
Dose Combination for Erdafitinib + Cetrelimab Cohort
Erdafitinib and cetrelimab (240 mg) will be administered either in the Standard (Cohort A) or 
Alternative (Cohort B) regimens. The dose of cetrelimab is increased to 480 mg every 4 weeks at 
Cycle 5.
The dose of study drug in each combination cohort/arm is shown in Appendix 1 Table 4.

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Section 6.5 Toxicity Due to One Study Drug and Continuation of Treatment
Page 101
Section 7 Treatment Compliance
Page 101
Section 8 Concomitant Therapy
Page 102
Section 9 Study Evaluations
Page 105
Section 9.1 Study Procedures
Page 105
Section 9.2 Efficacy Evaluations
Page 108
Section 9.3 Pharmacokinetics and Immunogenicity
Page 110
Section 9.4 Pharmacodynamic Evaluations
Page 111
Section 9.5 Predictive and Exploratory Biomarkers
Page 111
Section 9.6 Safety Evaluations
Page 113
Section 9.7 Sample Collection and Handling
Page 117
Section 10 Subject Completion/Discontinuation of Study 
Treatment/Withdrawal From the Study
Page 117
Section 11 Statistical Methods
Page 118
Section 12 Adverse Event Reporting
Page 123
Section 13 Product Quality Complaint Handling
Page 130
Section 14 Study Drug Information
Page 130
Section 15 Study-Specific Materials
Page 133
Section 16 Ethical Aspects
Page 133
Section 17 Administration Requirements
Page 138

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APPENDIX 2:
PHASE 1B ERDAFITINIB+ CETRELIMAB + PLATINUM 
(CISPLATIN OR CARBOPLATIN) CHEMOTHERAPY
1.
INTRODUCTION.............................................................................................................................. 201
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS......................................................................... 201
3.
STUDY DESIGN AND RATIONALE ............................................................................................... 202
3.1.
Overview of Study Design............................................................................................................ 202
3.1.1.
Phase 1b for Erdafitinib + Cetrelimab + Platinum (Cisplatin or Carboplatin) 
Chemotherapy Cohort .............................................................................................................. 202
3.2.
Study Design and Starting Dose Rationale.................................................................................. 204
3.2.1.
Rationale for the Combination of Erdafitinib, Cetrelimab, and Platinum (Cisplatin or 
Carboplatin) Chemotherapy ..................................................................................................... 204
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D................................................... 204
3.3.1.
Definition of Dose-Limiting Toxicity for Phase 1b (Dose Escalation) ....................................... 204
3.3.2.
Determination of the Phase 1b RP2D Regimen and Alternative Dosing Schedules ............... 205
3.4.
Study Evaluation Team................................................................................................................ 206
4.
SUBJECT POPULATION................................................................................................................ 206
4.1.
Inclusion Criteria .......................................................................................................................... 206
4.2.
Exclusion Criteria ......................................................................................................................... 211
5.
TREATMENT ALLOCATION AND BLINDING............................................................................... 215
6.
DOSAGE AND ADMINISTRATION ................................................................................................ 215
6.1.
Dose Combination for Erdafitinib + Cetrelimab + Platinum Chemotherapy Cohort..................... 215
6.2.
Administration of Erdafitinib ......................................................................................................... 216
6.3.
Administration of Cetrelimab........................................................................................................ 216
6.4.
Administration of Platinum Chemotherapy (Cisplatin or Carboplatin) ......................................... 216
6.4.1.
Cisplatin .................................................................................................................................... 216
6.4.2.
Carboplatin ............................................................................................................................... 216
6.4.3.
Antiemetic Therapy and Supportive Care Guidelines for Platinum Chemotherapy ................. 217
6.4.4.
Dose Modification, Dose Delays, and Retreatment Criteria for Platinum Chemotherapy........ 217
6.4.5.
Guidance for Specific Platinum Chemotherapy Toxicities........................................................ 219
6.4.6.
Platinum Chemotherapy Associated Toxicities Leading to Discontinuation of Study 
Treatment ................................................................................................................................. 219

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3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
Refer to Section 3.1 of the main body of the protocol.
3.1.1.
Phase 1b for Erdafitinib + Cetrelimab + Platinum (Cisplatin or 
Carboplatin) Chemotherapy Cohort
The Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort represents the dose 
escalation part of the study. A Modified Toxicity Probability Interval method, mTPI-2, (Guo 2017)
will be used by the Study Evaluation Team (SET, Section 3.4) to guide the dose escalation and 
RP2D(s) regimen recommendations (see Section 11.2, Attachment 1 and the SET charter). The 
expected number of subjects to be treated in the Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort is approximately 40. Three subjects (either wild-type or with select FGFR
gene alterations) will be enrolled in the initial erdafitinib + cetrelimab + cisplatin dose level 
(50 mg/m2). If the starting dose is safe, 6 additional subjects will be enrolled into the escalated 
dose of cisplatin (60 mg/m2). Out of 6 subjects, up to 3 subjects can be wild-type and the other 
subjects should be with select FGFR gene alterations. Wild-type is defined as subjects without 
FGFR gene alteration and subjects with FGFR gene alterations other than the select FGFR 
alterations described in Table 4. Approximately 10 additional subjects with select FGFR gene 
alterations will be enrolled at the MTD for erdafitinib + cetrelimab + cisplatin.
Three subjects (either wild-type or with select FGFR gene alterations) will be enrolled in the initial 
erdafitinib + cetrelimab + carboplatin dose level (AUC4 mg/mL/min). If the starting dose is safe, 
6 additional subjects will be enrolled into the escalated dose of carboplatin (AUC5 mg/mL/min). 
Out of 6 subjects, up to 3 subjects can be wild-type and the other subjects should be with select 
FGFR gene alterations. Approximately 10 additional subjects with select FGFR gene alterations 
will be enrolled at the MTD for erdafitinib + cetrelimab + carboplatin.
An overview of dose levels of the Phase 1b erdafitinib + cetrelimab + platinum (cisplatin or 
carboplatin) chemotherapy cohort is described in Figure 2.The dose levels within the platinum 
chemotherapy cohort are:
Erdafitinib + cetrelimab + cisplatin (DL2C or DL2C1)
Erdafitinib, cetrelimab and cisplatin start concurrently on C1D1. A maximum of 4 cycles of 
cisplatin will be administered. The DLT period is 2 cycles (6 weeks).
and
Erdafitinib + cetrelimab + carboplatin (DL2D or DL2D1)
Erdafitinib, cetrelimab and carboplatin start concurrently on C1D1. A maximum of 4 cycles of 
carboplatin will be administered. The DLT period is 2 cycles (6 weeks).
Refer to Appendix 2 Table 4 for an overview of the Phase 1b: erdafitinib + cetrelimab + platinum 
chemotherapy dose levels.

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Erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy cohort:
The starting dose is 8 mg erdafitinib (no up-titration); 360 mg Q3W cetrelimab, and either 
50 mg/m2 Q3W for cisplatin (DL2C) or AUC 4mg/mL/min Q3W for carboplatin (DL2D).
If based on the rules below, dose escalation for cisplatin is DL2C to DL2C1.
If based on the rules below, dose escalation for carboplatin is DL2D to DL2D1.
The following rules for escalation apply for the Phase 1b erdafitinib + cetrelimab + platinum 
(cisplatin or carboplatin) chemotherapy cohort:

At least 3 subjects may be dosed in each dose level that will be explored.

A staggered enrollment strategy will be applied to the first 3 subjects in a dose level. A minimal 
interval of 24 hours between a subject's first dose will be required.

At least 3 subjects per dose level are required to complete the DLT evaluation period or be 
discontinued for DLT before the SET can determine the dose and schedule for the next dose 
cohort.

The SET will evaluate all available data including, but not limited to, PK, PD, safety, and 
preliminary anti-tumor activity, and will decide whether to escalate, stay at the current dose, 
or de-escalate the dose level based on the mTPI-2 guidelines outlined in Attachment 1. These 
are briefly explained for the case with 3 subjects treated at a specific dose of platinum (cisplatin 
or carboplatin) chemotherapy:

If no subject at a specific dose level of platinum (cisplatin or carboplatin) chemotherapy 
experiences a DLT, dose escalation may proceed. as guided by mTPI-2. The SET will confirm 
the dose level chosen for the next dose cohort.

If 1 out of 3 subjects at a specific dose level of platinum (cisplatin or carboplatin) chemotherapy 
experiences DLT during the DLT evaluation period, then the SET may decide to enroll additional 
subjects before escalating the dose of platinum-based chemotherapy.

If 2 out of 3 subjects at a specific dose level of platinum (cisplatin or carboplatin) chemotherapy 
experience DLT during the DLT evaluation period. The SET will confirm the dose level chosen 
for the next dose level.

If 3 out of 3 subjects at a specific dose level of platinum (cisplatin or carboplatin) chemotherapy 
experience DLT during the DLT evaluation period. The SET will confirm the dose level chosen 
for the next dose cohort.

Dose escalation guided by the SET may continue until the RP2D is identified.

The identification of the RP2D will be based on the totality of data from all dose cohorts tested.

The SET will determine whether to modify or terminate dose levels, include additional dose levels, 
change doses or schedules of either drug, modify the study conduct if deemed necessary, and select 
the RP2D regimen for Phase 2 based on the emerging data (see Section 3.4).

Intra-subject dose escalation is not allowed and subjects in Phase 1b erdafitinib + cetrelimab +
platinum chemotherapy dose levels will not be entered into Phase 2.

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3.2.
Study Design and Starting Dose Rationale
Refer to Section 3.2 of the main body of the protocol.
3.2.1.
Rationale for the Combination of Erdafitinib, Cetrelimab, and 
Platinum (Cisplatin or Carboplatin) Chemotherapy
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D
During Phase 1b, subjects will initially be enrolled into the starting dose of cisplatin or carboplatin 
(DL2C and DL2D) based on the mTPI-2 method. (Guo 2017) After the last subject in each group 
(minimum of 3 DLT evaluable subjects) has completed the DLT observation period or developed 
a DLT, the SET will evaluate all available safety data and make the decision whether to escalate, 
stay at the current dose or de-escalate the dose of platinum chemotherapy with the second group 
of subjects treated, based on the guidelines outlined in and in the SET charter. Based on emerging 
clinical data, the SET might decide to adjust the dose of cisplatin and/or carboplatin or terminate 
individual dose levels if deemed necessary. No intra-subject dose escalations will be allowed 
throughout this study.
3.3.1.
Definition of Dose-Limiting Toxicity for Phase 1b (Dose Escalation)
Toxicities will be graded for severity according to the NCI-CTCAE, version 5.0. Only toxicities 
that occur during the DLT evaluation period will be used to define DLTs and for dose escalation 
decisions, but toxicities that occur during the entire treatment period will be recorded and 
considered in decisions regarding the RP2D.
The DLT evaluation period for the Phase 1b erdafitinib + cetrelimab + platinum (cisplatin or 
carboplatin) chemotherapy cohort is defined as 2 full cycles (6 weeks) of erdafitinib, cetrelimab, 
and platinum chemotherapy from the start of the first erdafitinib dose.
If the subject receives more than 75% of any of the study drugs in the DLT evaluation period, the 
subject will be evaluable for DLT. If the subject received less than 75% of each assigned dose due 
to reasons other than toxicities (eg, disease progression, missed appointments, non-compliance, 
subject withdrawal), the subject may be replaced with a new subject. All available safety data from 
subjects will be taken into consideration by the SET. Dose-limiting toxicities are defined as any 
of the events listed in Appendix 2 Table 3.

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Subject safety will be monitored as indicated in Section 3.4. Cumulative safety evaluation will be 
performed after completion of Cycle 2 therapy for all subjects in each dose level (DL2C, DL2C1, 
DL2D, and DL2D1).
3.4.
Study Evaluation Team
Refer to Section 3.4 of the main body of the protocol.
4.
SUBJECT POPULATION
Adult subjects age 18 years and older with metastatic or locally advanced urothelial cancer who 
meet the molecular eligibility and full-study eligibility are eligible for the study. Screening 
assessments will be performed as indicated in the Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy Table and Events schedule (Appendix 2 Table 1). Molecular eligibility assessment 
may occur ≥28 days prior to administration of the study drugs.
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 should consult with the appropriate sponsor representative before enrolling a subject 
in the study. For a discussion of the statistical considerations of subject selection, refer to 
Section 11.1, 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.
2.

Criterion modified per Amendment 2
2.1 Histologic demonstration of transitional cell carcinoma of the urothelium. Variant 
urothelial carcinoma histologies such as glandular or squamous differentiation, or 
evolution to more aggressive phenotypes such as sarcomatoid or micropapillary 
change are acceptable.
3.

Criterion modified per Amendment 2
3.1 Metastatic or locally advanced urothelial cancer (Stage IV disease per AJCC Staging 
Guidelines)
4.

Criterion modified per Amendment 2

4.1 Criterion modified per Amendment 3
4.2 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Meet appropriate molecular eligibility 
criteria. Tumors must have at least one gene fusion or gene mutation as defined in Table 4.
Exception for Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: 
up to 3 subjects in each erdafitinib + cetrelimab + chemotherapy cohort at each dose 
level will be wild-type. Wild-type is defined as subjects without FGFR gene alteration 
and subjects with FGFR gene alterations other than the select FGFR alterations 

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described in Table 4. All other subjects must have at least one select FGFR alteration 
as defined in Table 4.
5.
Criterion modified per Amendment 2
5.1 Must have measurable disease by radiological imaging according to the Response 
Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline.
6.
Criterion modified per Amendment 2
6.1 Criterion modified per Amendment 3
6.2 Prior systemic therapy for metastatic urothelial cancer:
Phase 1b erdafitinib + cetrelimab cohort:
–
Any number of lines of prior therapy
Renal function for subjects must have a creatinine clearance (CrCl) ≥30 mL/min as calculated by 
Cockcroft-Gault (Attachment 8)
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
–
No prior systemic therapy for metastatic disease. 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 chemotherapy in the metastatic setting
–
Renal function for subjects must have a creatinine clearance (CrCl) 
≥30 mL/min to receive carboplatin and ≥60 mL/min to receive 
cisplatin as calculated by Cockcroft-Gault (Attachment 8)
Phase 2:
–
No prior systemic therapy for metastatic disease. 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 chemotherapy 
in the metastatic setting
–
Cisplatin-ineligible based on:

ECOG PS 0-1 AND at least one of the following criteria:
–
Renal function defined as creatinine clearance (CrCl) ˂60 mL/min as calculated 
by Cockcroft-Gault (Attachment 8) (Galsky 2011)
–
Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0.
–
Grade 2 or higher hearing loss per NCI-CTCAE version 5.0,
OR
–
ECOG PS 2
7.
Criterion modified per Amendment 2
7.1 Criterion modified per Amendment 3
7.2 ECOG PS Grade of (see Attachment 3) as defined below:
Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2

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oocytes) or sperm, respectively, during the study and for 5 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception associated with 
inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized 
partner;
–
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.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes, a 
woman must begin a highly effective method of contraception, as described throughout the inclusion 
criteria. If reproductive status is questionable, additional evaluation should be considered. It should be 
noted that interaction between hormonal contraception and the combination of the study drugs have not 
been studied. Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of true sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, 
post-ovulation methods], declaration of abstinence for the duration of exposure to the study drugs, and 
withdrawal are not acceptable methods of contraception).
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
Before the first dose of study drug:
Women of childbearing potential (defined as: fertile, following menarche and until 
becoming post-menopausal unless permanently sterile as a result of hysterectomy, 
bilateral salpingectomy, or bilateral oophorectomy) and fertile men who are sexually 
active must agree to use a highly effective method of contraception (<1%/year failure 
rate) during the study and for 6 months after the last dose of study drug. For men who 
are sexually active with women of childbearing potential: agree to use a condom with 
spermicidal foam/gel/film/cream/suppository during the study and for 6 months after 
the last dose of study drug. Contraception must be consistent with local regulations 
regarding the use of birth control methods for subjects participating in clinical trials. 
Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, 
during the study and for 6 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception 
associated with inhibition of ovulation; intrauterine device; intrauterine hormone-
releasing system; vasectomized partner;
–
user-dependent methods: combined (estrogen- and progestogen-containing) 

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hormonal contraception associated with inhibition of ovulation: oral, intravaginal, 
and transdermal; progestogen-only hormone contraception associated with 
inhibition of ovulation: oral and injectable.
Note: If the childbearing potential changes after start of the study or the risk of 
pregnancy changes, a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria. If reproductive status is questionable, 
additional evaluation should be considered. It should be noted that interaction between 
hormonal contraception and the combination of the study drugs have not been studied. 
Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of true sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, post-
ovulation methods], declaration of abstinence for the duration of exposure to the study 
drugs, and withdrawal are not acceptable methods of contraception).
10.
Women of childbearing potential must have a negative pregnancy test at Screening 
within ≤7 days of C1D1 (first dose of study drug) using a highly sensitive pregnancy 
test (serum -human chorionic gonadotropin [-hCG]); see Section 9.6.4).
11.
Sign an informed consent form indicating that he or she understands the purpose of and 
procedures required for the study, and is willing and able to participate in the study. 
Consent is to be obtained prior to the initiation of any study-related tests or procedures 
that are not part of standard of care for the subject’s disease.
12.
Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
4.2.
Exclusion Criteria
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 C1D1. For Phase 1b, subjects who have 
received the following prior anti-tumor therapy:

Received nitrosoureas and mitomycin C within 6 weeks. 
2.
Criterion modified per Amendment 3
2.1 Phase 1b erdafitinib + cetrelimab cohort:

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
Chemotherapy within 3 weeks of C1D1.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2:

Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given 
>12 months prior to recurrent disease progression and did not result in drug-related 
toxicity leading to treatment discontinuation.
3.
Criterion modified per Amendment 2
3.1 Criterion modified per Amendment 3
3.2 Prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. Prior neoadjuvant/adjuvant 
checkpoint inhibitor therapy is allowed if the last dose was given >12 months prior to 
recurrent disease progression and did not result in drug-related toxicity leading to 
treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also 
allowed.
4.
Criterion modified per Amendment 2
4.1 Active malignancies requiring concurrent therapy other than urothelial cancer.
5.
Symptomatic central nervous system metastases.
6.
Prior FGFR inhibitor treatment.
7.
Radiation therapy ≤30 days prior to planned C1D1. 
8.
Criterion modified per Amendment 2
8.1 Criterion modified per Amendment 3
8.2 History of uncontrolled cardiovascular disease including:

Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de 
Pointes, cardiac arrest, or known congestive heart failure Class III-V (Attachment 
6) within the preceding 3 months; cerebrovascular accident or transient ischemic 
attack within the preceding 3 months.
9.
Known to be seropositive for human immunodeficiency virus or acquired immune 
deficiency syndrome.
10.
Any of the following:

Evidence of serious active viral, bacterial, or uncontrolled systemic fungal 
infection.

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
Active autoimmune disease or a documented history of autoimmune disease that 
requires systemic steroids or immunosuppressive agents.
Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception 
to this rule. Subjects that require intermittent use of bronchodilators or local steroid 
injections would not be excluded from the study. Subjects with hypothyroidism stable 
on hormone replacement will not be excluded from the study. Subjects with a history 
of transient autoimmune manifestations of an acute infectious disease that resolved 
upon treatment of the infectious agent (eg, acute Lyme arthritis) will not be excluded 
from the study.

Grade 3 or higher toxicity effects from previous treatment with immunotherapy.

Psychiatric conditions (eg, alcohol or drug abuse), dementia, or altered mental 
status.

Any other issue that would impair the ability of the subject to receive or tolerate 
the planned treatment at the investigational site, to understand informed consent or 
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.
11.
Pulmonary compromise requiring supplemental oxygen use to maintain adequate 
oxygenation.
12.
Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface 
antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) 
positivity at Screening. If positive, further testing of quantitative levels to rule out 
active infection is required (see Attachment 2).
13.
Criterion modified per Amendment 3
13.1
Phase 1b erdafitinib + cetrelimab and Phase 1b erdafitinib + cetrelimab + platinum
chemotherapy cohort: Not recovered from reversible toxicity of prior anticancer 
therapy (except toxicities which are considered by the investigator as not clinically 
significant, such as alopecia, skin discoloration, or Grade 1 hearing loss or 
neuropathy).
Phase 2: Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are 
considered by the investigator as not clinically significant such as alopecia, or skin discoloration).
14.
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, 
known gastric ulcers, or unhealed incisions.
15.
Criterion modified per Amendment 2
15.1 Allergies, hypersensitivity, or intolerance to protein-based therapies or with a 
history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or 

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immune-mediated thrombocytopenia or anemia), or to excipients of erdafitinib or 
cetrelimab (see the Investigator’s Brochures for a list of excipients).
16.
Criterion modified per Amendment 2
16.1 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment 
(RPED) of any Grade.
17.
Criterion deleted per Amendment 2
18.
Criterion modified per Amendment 2
18.1 Use of immunosuppressant agents, including, but not limited to: systemic 
corticosteroids at doses exceeding 10 mg/day of prednisone or its equivalent, 
methotrexate, cyclosporine, azathioprine, and tumor necrosis factor α (TNF-α) 
blockers, within 2 weeks before the planned first dose of study drug.
19.
Vaccinated with a live attenuated vaccine within 28 days prior to the first dose of study 
drug and for 3 months after receiving the last dose of study drug. Annual inactivated 
influenza vaccine is permitted.
20.
Criterion modified per Amendment 3
20.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Pregnant or breast-feeding, or planning to 
become pregnant while enrolled in this study or within 5 months after receiving the last dose of study 
drug.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Pregnant or 
breast-feeding, or planning to become pregnant while enrolled in this study or within 
6 months after receiving the last dose of study drug.
21.
Criterion modified per Amendment 3
21.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Plans to father a child while enrolled in this 
study or within 5 months after receiving the last dose of study drug.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Plans to father 
a child while enrolled in this study or within 6 months after receiving the last dose of 
study drug.
22.
Criterion modified per Amendment 2
22.1 Major surgery within 4 weeks of enrollment, or inadequate recovery from the 
toxicity and/or complications from the intervention prior to starting therapy. 

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a Additional dosing schedules may be explored if recommended by the SET and agreed upon by the sponsor.
b The cetrelimab dosing schedule can be adjusted if recommended by the SET and agreed upon by the sponsor.
c On days that all study drugs will be administered, the sequence of administration will be erdafitinib first, followed by cetrelimab 
and then platinum chemotherapy
d Erdafitinib + cetrelimab can continue every 3 weeks after a maximum of 4 cycles of platinum chemotherapy.
e See Section 3.1.1 of Appendix 2 for dose escalation.
6.2.
Administration of Erdafitinib
Refer to Section 6.2 of the main body of the protocol.
6.3.
Administration of Cetrelimab
Refer to Section 6.3 of the main body of the protocol.
6.4.
Administration of Platinum Chemotherapy (Cisplatin or Carboplatin)
Standard chemotherapeutic agents will be prepared and administered as per the approved product 
label at the doses indicated below.
6.4.1.
Cisplatin
The starting dose level for of cisplatin (DL2C) is 50 mg/m2 IV Q3W. The dose level escalation 
rules for cisplatin are described in Section 3.1.1 of this appendix. Dosing with cisplatin should be 
immediately preceded and followed by hydration procedures. Supportive premedication and 
administration procedures for cisplatin are to align with the cisplatin label and local practice. A 
maximum of 4 cycles of cisplatin are to be administered to the subject. Erdafitinib and cetrelimab 
will continue after the subject receives 4 cycles of cisplatin.
6.4.2.
Carboplatin
The starting dose level for carboplatin (DL2D) is AUC 4 mg/mL/min Q3W. The dose level 
escalation rules for carboplatin are described in Section 3.1.1 of this appendix. Supportive 
premedication and administration procedures for carboplatin are to align with the carboplatin label 
and local practice. A maximum of 4 cycles of carboplatin are to be administered to the subject. 
Erdafitinib and cetrelimab will continue after the subject receives 4 cycles of carboplatin.
Carboplatin dosing is calculated via the Calvert formula. Carboplatin dosing is not to exceed 
600 mg for AUC4 dose level, and 750 mg for AUC5 dose level.
Calvert Formula:
Total Dose (mg) = (target AUC) x (CrCl + 25)
The estimated GFR used in the Calvert formula should not exceed 125 mL/min.
The maximum carboplatin dose (mg) = target AUC 4 (mg/min/mL) x (125 +25) = 4 x 150 mL/min 
is 600 mg.
The calculation of the creatinine clearance can be found in Attachment 8.

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6.4.3.
Antiemetic Therapy and Supportive Care Guidelines for Platinum 
Chemotherapy
Antiemetic therapy administered on days of platinum chemotherapy should follow Multinational 
Association for Supportive Care in Cancer (MASCC) guidelines (and should, for the first 4 
cycles, include a 5-HT3 receptor antagonist, dexamethasone (or equivalent) and aprepitant (or 
equivalent) as per the MASCC guidelines.
Routine primary prophylaxis to treat immunosuppression is not permitted for subjects who are 
under evaluation for DLTs. For the use of CSFs after the DLT period ends, utilize (NCCN/EORTC 
2018) guidelines. However, subjects should receive appropriate supportive care measures as
deemed necessary by the treating investigator. For each disorder, attempts should be made to
rule out other causes such as metastatic disease or bacterial or viral infection, which might require
additional supportive care.
6.4.4.
Dose Modification, Dose Delays, and Retreatment Criteria for 
Platinum Chemotherapy
Dose modifications must be based on the maximum toxicity experienced during a cycle. The
investigator may attribute each toxicity event to platinum chemotherapy alone or to the
combination of study drugs. Dose modification of the platinum chemotherapy agent and not the
other agent(s) is appropriate if, in the opinion of the investigator, the toxicity is clearly related to
platinum chemotherapy. If the toxicity is related to a combination of agents, all relevant 
agents should be reduced (if applicable), interrupted or discontinued according to the
recommended dose modifications for that agent. See Section 6.2.2 for the dose modification, 
dose delay, and retreatment instruction for erdafitinib. See Section 6.3.1 and 6.3.2 for instructions 
regarding the retreatment and dose delay of cetrelimab, respectively.
If a subject experiences several toxicities and there are conflicting recommendations, the most 
conservative dose adjustment recommended should be followed (dose reduction appropriate to the 
most severe toxicity). Subjects can have a maximum of 2 dose modifications (if applicable) of 
platinum chemotherapy throughout the course of the study for toxicities. Subjects who require a
3rd dose modification to any particular component will have that agent discontinued.
Recommended dose modifications for platinum
chemotherapy for hematologic and 
non-hematologic toxicity are described in Appendix 2 Table 5 and Appendix 2 Table 6, 
respectively. Appendix 2 Table 5 and Appendix 2 Table 6 serve as a guide and do not replace
investigator judgment and applicable local label recommendations if more stringent.
Appendix 2 Table 5: Recommended Dose Modifications for Platinum Chemotherapy: Hematological Toxicity
Cisplatin/Carboplatin
Platelets (x103 cells/microliter)
ANC (x103 cells/mm3)
Dose modification (DM)
≥50 AND
≥0.5
DM 0
DM 0
≥50 AND
˂0.5
DM -1
DM -1
˂50 without bleeding AND
ANY
DM -1
DM -1
˂50 with Grade ≥ 2 bleeding AND
ANY
DM -2
DM -2
ANY AND
˂1.0 + fever ≥38.5C (101F)
DM -1
DM -1

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for each new cycle may be delayed if the scheduled off-drug periods are not adequate to allow for 
recovery to Grade ≤1 or the baseline status of the subject.
If a subject permanently discontinues 1 of the study drugs, the subject may continue to receive the 
other study drug(s) if investigator believes that the subject derives clinical benefit upon 
consultation with the sponsor’s responsible medical monitor. Communication with the sponsor’s 
responsible medical monitor including the final decision must be documented and retained in the 
sponsor’s trial master file and in the investigator’s study files.
6.4.5.
Guidance for Specific Platinum Chemotherapy Toxicities
Cisplatin
The toxicity profile for cisplatin is described in the full prescribing information and labeling in the 
respective current US prescribing information, EU SmPC, or equivalent document for the specific 
region/country.
For subjects in DL2C, DL2C1 and DL2C2, cisplatin may produce cumulative nephrotoxicity 
which is potentiated by aminoglycoside antibiotics. Serum creatinine, blood urea nitrogen (BUN), 
creatinine clearance, magnesium, sodium, potassium, and calcium levels should be measured prior 
to initiating therapy and prior to each dose of cisplatin. Adequate renal function must be 
documented prior to receiving the next dose of cisplatin.
Audiometry will be performed for cis-ineligible ONLY if hearing loss is the single reason for cis-
ineligibility. Audiometry will be performed as clinically indicated as ototoxicity is cumulative. 
Hearing loss during the study should be reported as an AE and graded according to CTCAE version 
5.0.
Carboplatin
The toxicity profile for carboplatin is described in the full prescribing information and labeling in 
the respective current US prescribing information, EU SmPC, or equivalent document for the 
specific region/country.
For subjects in DL2D and DL2D1, bone marrow suppression (leukopenia, neutropenia, and 
thrombocytopenia) is dose-dependent and is also a DLT. Peripheral blood counts should be 
monitored frequently and, when appropriate, until recovery is achieved. Carboplatin can induce 
emesis, which can be more severe in patients previously receiving emetogenic therapy.
6.4.6.
Platinum Chemotherapy Associated Toxicities Leading to 
Discontinuation of Study Treatment
The subject must discontinue platinum chemotherapy if:

the subject experiences a Grade 3 or 4 unacceptable AE that does not resolve to Grade ≤ 1 
within 7 days with medical management. Unacceptable AEs are described in Appendix 2 
Table 8.

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
the subject experiences any other intercurrent illness that prevents further administration 
of treatment, the subject must discontinue study treatment.
Appendix 2 Table 8:  Unacceptable Adverse Events Leading to Discontinuation of Platinum Chemotherapy
Grade 4 Hematologic toxicities
Grade 3 Non- hematologic toxicities
Complete Blood Count:
leukopenia
thrombocytopenia
neutropenia
anemia
Nephrotoxicity:
elevation in BUN and creatinine
elevation in serum uric acid
decrease in CrCl
Serum electrolyte disturbances:
hypomagnesemia
hypocalcemia
hyponatremia
hypokalemia
hypophosphatemia
Ototoxicity:
tinnitus
bilateral hearing loss
dizziness
Gastrointestinal:
nausea
vomiting 
For more information regarding the following sections, please 
refer to the main body of the protocol.
Page #
Section 7 Treatment Compliance
Page 101
Section 8 Concomitant Therapy
Page 102
Section 9 Study Evaluations
Page 105
Section 9.1 Study Procedures
Page 105
Section 9.2 Efficacy Evaluations
Page 108
Section 9.3 Pharmacokinetics and Immunogenicity
Page 110
Section 9.4 Pharmacodynamic Evaluations
Page 111
Section 9.5 Predictive and Exploratory Biomarkers
Page 111
Section 9.6 Safety Evaluations
Page 113
Section 9.7 Sample Collection and Handling
Page 117
Section 10 Subject Completion/Discontinuation of Study 
Treatment/Withdrawal From the Study
Page 117

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Section 11 Statistical Methods
Page 118
Section 12 Adverse Event Reporting
Page 123
Section 13 Product Quality Complaint Handling
Page 130
Section 14 Study Drug Information
Page 130
Section 15 Study-Specific Materials
Page 133
Section 16 Ethical Aspects
Page 133
Section 17 Administration Requirements
Page 138

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APPENDIX 3:
PHASE 2 ERDAFITINIB +/ -CETRELIMAB COHORT
1.
INTRODUCTION.............................................................................................................................. 233
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS......................................................................... 233
2.1.
Objectives and Endpoints for Phase 2 (Dose Expansion)........................................................... 233
2.2.
Hypothesis ................................................................................................................................... 233
3.
STUDY DESIGN AND RATIONALE ............................................................................................... 234
3.1.
Overview of Study Design............................................................................................................ 234
3.1.1.
Phase 1b................................................................................................................................... 234
3.1.2.
Phase 2: Erdafitinib +/- Cetrelimab Cohort............................................................................... 234
3.2.
Study Design and Starting Dose Rationale.................................................................................. 234
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D................................................... 234
3.4.
Study Evaluation Team................................................................................................................ 234
4.
SUBJECT POPULATION................................................................................................................ 234
4.1.
Inclusion Criteria .......................................................................................................................... 235
4.2.
Exclusion Criteria ......................................................................................................................... 240
5.
TREATMENT ALLOCATION AND BLINDING............................................................................... 244
6.
DOSAGE AND ADMINISTRATION ................................................................................................ 244
6.1.
Dose Combination for Erdafitinib +/- Cetrelimab Arms................................................................ 244

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3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
Refer to Section 3.1 of the main body of the protocol.
3.1.1.
Phase 1b
Not applicable to the Phase 2 erdafitinib +/- cetrelimab cohort.
3.1.2.
Phase 2: Erdafitinib +/- Cetrelimab Cohort
An overview of the Phase 2 dose expansion cohort is described in Figure 3.
In Phase 2 (dose expansion), approximately 90 subjects with metastatic or locally advanced 
urothelial cancer with select FGFR gene alterations based on molecular testing who meet the 
definition of cisplatin-ineligible and have not had prior systemic therapy for metastatic disease will 
be stratified by ECOG PS (0-1 versus 2) and then assigned randomly (1:1 ratio) to either the 
erdafitinib monotherapy treatment (Arm A), or the combination treatment of erdafitinib and 
cetrelimab (Arm B). To further characterize safety and clinical activity of the erdafitinib and 
cetrelimab (Arm B).
A DRC will be commissioned for Phase 2 of this study. Based on emerging safety data, on 
12 May 2020, the DRC recommended to remove the requirement for up-titration from the 
erdafitinib + cetrelimab combination. The DRC also made a recommendation to close Dose level 
2 in Phase 1b and focus enrollment efforts into the Phase 2 part of the study. Therefore, Arm B 
will no longer include up-titration for erdafitinib.
Refer to Section 11.10 of the main body of the protocol and the DRC charter for details regarding 
the composition and scope of the DRC.
Refer to Appendix 3 Table 3 for an overview of the Phase 2 dosing administration of erdafitinib 
and cetrelimab.
3.2.
Study Design and Starting Dose Rationale
Refer to Section 3.2 of the main body of the protocol.
3.3.
Dose-Limiting Toxicity Evaluation and Determination of RP2D
Not applicable to the Phase 2 erdafitinib +/- cetrelimab cohort.
3.4.
Study Evaluation Team
Not applicable to the Phase 2 erdafitinib +/- cetrelimab cohort.
4.
SUBJECT POPULATION
Adult subjects age 18 years and older with metastatic or locally advanced urothelial cancer who 
meet the molecular eligibility and full-study eligibility are eligible for the study. Screening 

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assessments will be performed as indicated in the Phase 2 erdafitinib +/- cetrelimab Time and 
Events Schedule Appendix 3 Table 1. Molecular eligibility assessment may occur ≥28 days prior 
to administration of the study drugs.
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 should consult with the appropriate sponsor representative before enrolling a subject 
in the study. For a discussion of the statistical considerations of subject selection, refer to 
Section 11.1, 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.
2.
Criterion modified per Amendment 2
2.1 Histologic demonstration of transitional cell carcinoma of the urothelium. Variant 
urothelial carcinoma histologies such as glandular or squamous differentiation, or 
evolution to more aggressive phenotypes such as sarcomatoid or micropapillary 
change are acceptable.
3.
Criterion modified per Amendment 2
3.1 Metastatic or locally advanced urothelial cancer (Stage IV disease per AJCC Staging 
Guidelines)
4.
Criterion modified per Amendment 2
4.1 Criterion modified per Amendment 3
4.2 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Meet appropriate molecular 
eligibility criteria. Tumors must have at least one gene fusion or gene mutation as 
defined in Table 4.
Exception for Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: up to 3 subjects in each 
erdafitinib + cetrelimab + chemotherapy cohort at each dose level will be wild-type. Wild-type is defined 
as subjects without FGFR gene alteration and subjects with FGFR gene alterations other than the select 
FGFR alterations described in Table 4. All other subjects must have at least one select FGFR alteration 
as defined in Table 4.
5.
Criterion modified per Amendment 2
5.1 Must have measurable disease by radiological imaging according to the Response 
Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline.
6.
Criterion modified per Amendment 2
6.1 Criterion modified per Amendment 3


6.2 Prior systemic therapy for metastatic urothelial cancer:

Phase 1b erdafitinib + cetrelimab cohort:

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–
Any number of lines of prior therapy
–
Renal function for subjects must have a creatinine clearance (CrCl) ≥30 mL/min 
as calculated by Cockcroft-Gault (Attachment 8)

Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
–
No prior systemic therapy for metastatic disease. 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 chemotherapy 
in the metastatic setting
–
Renal function for subjects must have a creatinine clearance (CrCl) ≥30 mL/min 
to receive carboplatin and ≥60 mL/min to receive cisplatin as calculated by 
Cockcroft-Gault (Attachment 8)

Phase 2:
–
No prior systemic therapy for metastatic disease. 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 chemotherapy in the metastatic setting.
–
Cisplatin-ineligible based on:

ECOG PS 0-1 AND at least one of the following criteria:
–
Renal function defined as creatinine clearance (CrCl) ˂60 mL/min 
as calculated by Cockcroft-Gault (Attachment 8) (Galsky 2011)
–
Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 
5.0.
–
Grade 2 or higher hearing loss per NCI-CTCAE version 5.0,

OR
–
ECOG PS 2
7.
Criterion modified per Amendment 2
7.1 Criterion modified per Amendment 3
7.2 ECOG PS Grade of (see Attachment 3) as defined below:
Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and ECOG 
0-2 for carboplatin.
Phase 2: ECOG 0-2
8.
Criterion modified per Amendment 1
8.1 Criterion modified per Amendment 2
8.2 Criterion modified per Amendment 3
8.3 Adequate organ function at Screening defined as follows:

Phase 1b erdafitinib + cetrelimab cohort and Phase 2

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regarding the use of birth control methods for subjects participating in clinical trials. 
Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, 
during the study and for 5 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception 
associated with inhibition of ovulation; intrauterine device; intrauterine 
hormone-releasing system; vasectomized partner;
–
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.
Note: If the childbearing potential changes after start of the study or the risk of 
pregnancy changes, a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria. If reproductive status is questionable, 
additional evaluation should be considered. It should be noted that interaction between 
hormonal contraception and the combination of the study drugs have not been studied. 
Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of true sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, post-
ovulation methods], declaration of abstinence for the duration of exposure to the study 
drugs, and withdrawal are not acceptable methods of contraception).
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort:
Before the first dose of study drug:
Women of childbearing potential (defined as: fertile, following menarche and until becoming post-
menopausal unless permanently sterile as a result of hysterectomy, bilateral salpingectomy, or bilateral 
oophorectomy) and fertile men who are sexually active must agree to use a highly effective method of 
contraception (<1%/year failure rate) during the study and for 6 months after the last dose of study drug. 
For men who are sexually active with women of childbearing potential: agree to use a condom with 
spermicidal foam/gel/film/cream/suppository during the study and for 6 months after the last dose of 
study drug. Contraception must be consistent with local regulations regarding the use of birth control 
methods for subjects participating in clinical trials. Women and men must agree not to donate eggs (ova, 
oocytes) or sperm, respectively, during the study and for 6 months after the last dose of study drug.
Examples of highly effective methods include:
–
user-independent methods: implantable progestogen-only hormone contraception associated with 
inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized 

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partner;
–
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.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes, a 
woman must begin a highly effective method of contraception, as described throughout the inclusion 
criteria. If reproductive status is questionable, additional evaluation should be considered. It should be 
noted that interaction between hormonal contraception and the combination of the study drugs have not 
been studied. Therefore, it is unknown whether the study drugs may reduce the efficacy of the 
contraceptive method.
–
Sexual abstinence
(True sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of true sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, 
post-ovulation methods], declaration of abstinence for the duration of exposure to the study drugs, and 
withdrawal are not acceptable methods of contraception).
10.
Women of childbearing potential must have a negative pregnancy test at Screening 
within ≤7 days of C1D1 (first dose of study drug) using a highly sensitive pregnancy 
test (serum -human chorionic gonadotropin [-hCG]); see Section 9.6.4).
11.
Sign an informed consent form indicating that he or she understands the purpose of and 
procedures required for the study, and is willing and able to participate in the study. 
Consent is to be obtained prior to the initiation of any study-related tests or procedures 
that are not part of standard of care for the subject’s disease.
12.
Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
4.2.
Exclusion Criteria
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 C1D1. For Phase 1b, subjects who have 
received the following prior anti-tumor therapy:

Received nitrosoureas and mitomycin C within 6 weeks. 
2.
Criterion modified per Amendment 3
2.1 Phase 1b erdafitinib + cetrelimab cohort:

Chemotherapy within 3 weeks of C1D1.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2:

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
Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given 
>12 months prior to recurrent disease progression and did not result in drug-related 
toxicity leading to treatment discontinuation.
3.
Criterion modified per Amendment 2
3.1 Criterion modified per Amendment 3
3.2 Prior anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy. Prior neoadjuvant/adjuvant 
checkpoint inhibitor therapy is allowed if the last dose was given >12 months prior to 
recurrent disease progression and did not result in drug-related toxicity leading to 
treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also 
allowed.
4.
Criterion modified per Amendment 2
4.1 Active malignancies requiring concurrent therapy other than urothelial cancer.
5.
Symptomatic central nervous system metastases.
6.
Prior FGFR inhibitor treatment.
7.
Radiation therapy ≤30 days prior to planned C1D1. 
8.
Criterion modified per Amendment 2
8.1 Criterion modified per Amendment 3
8.2 History of uncontrolled cardiovascular disease including:

Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de 
Pointes, cardiac arrest, or known congestive heart failure Class III-V (Attachment 
6) within the preceding 3 months; cerebrovascular accident or transient ischemic 
attack within the preceding 3 months.
9.
Known to be seropositive for human immunodeficiency virus or acquired immune 
deficiency syndrome.
10.
Any of the following:

Evidence of serious active viral, bacterial, or uncontrolled systemic fungal 
infection.

Active autoimmune disease or a documented history of autoimmune disease that 
requires systemic steroids or immunosuppressive agents.
Note: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception 
to this rule. Subjects that require intermittent use of bronchodilators or local steroid 

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injections would not be excluded from the study. Subjects with hypothyroidism stable 
on hormone replacement will not be excluded from the study. Subjects with a history 
of transient autoimmune manifestations of an acute infectious disease that resolved 
upon treatment of the infectious agent (eg, acute Lyme arthritis) will not be excluded 
from the study.

Grade 3 or higher toxicity effects from previous treatment with immunotherapy.

Psychiatric conditions (eg, alcohol or drug abuse), dementia, or altered mental 
status.

Any other issue that would impair the ability of the subject to receive or tolerate 
the planned treatment at the investigational site, to understand informed consent or 
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.
11.
Pulmonary compromise requiring supplemental oxygen use to maintain adequate 
oxygenation.
12.
Active or chronic hepatitis B or hepatitis C disease as determined by hepatitis B surface 
antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody (anti-HCV) 
positivity at Screening. If positive, further testing of quantitative levels to rule out 
active infection is required (see Attachment 2).
13.
Criterion modified per Amendment 3
13.1
Phase 1b erdafitinib + cetrelimab and Phase 1b erdafitinib + cetrelimab + platinum 
chemotherapy cohort: Not recovered from reversible toxicity of prior anticancer therapy (except 
toxicities which are considered by the investigator as not clinically significant, such as alopecia, skin 
discoloration, or Grade 1 hearing loss or neuropathy).
Phase 2: Not recovered from reversible toxicity of prior anticancer therapy (except 
toxicities which are considered by the investigator as not clinically significant such as 
alopecia, or skin discoloration).
14.
Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, 
known gastric ulcers, or unhealed incisions.
15.
Criterion modified per Amendment 2
15.1 Allergies, hypersensitivity, or intolerance to protein-based therapies or with a 
history of any significant drug allergy (such as anaphylaxis, hepatotoxicity, or 
immune-mediated thrombocytopenia or anemia), or to excipients of erdafitinib or 
cetrelimab (see the Investigator’s Brochures for a list of excipients).

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16.
Criterion modified per Amendment 2
16.1 Current central serous retinopathy (CSR) or retinal pigment epithelial detachment 
(RPED) of any Grade.
17.
Criterion deleted per Amendment 2
18.
Criterion modified per Amendment 2
18.1 Use of immunosuppressant agents, including, but not limited to: systemic 
corticosteroids at doses exceeding 10 mg/day of prednisone or its equivalent, 
methotrexate, cyclosporine, azathioprine, and tumor necrosis factor α (TNF-α) 
blockers, within 2 weeks before the planned first dose of study drug.
19.
Vaccinated with a live attenuated vaccine within 28 days prior to the first dose of study 
drug and for 3 months after receiving the last dose of study drug. Annual inactivated 
influenza vaccine is permitted.
20.
Criterion modified per Amendment 3
20.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Pregnant or breast-feeding, or 
planning to become pregnant while enrolled in this study or within 5 months after 
receiving the last dose of study drug.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Pregnant or breast-feeding, 
or planning to become pregnant while enrolled in this study or within 6 months after receiving
the last dose of study drug.
21.
Criterion modified per Amendment 3
21.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: Plans to father a child while 
enrolled in this study or within 5 months after receiving the last dose of study drug.
Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: Plans to father a child while enrolled 
in this study or within 6 months after receiving the last dose of study drug.
22.
Criterion modified per Amendment 2
22.1 Major surgery within 4 weeks of enrollment, or inadequate recovery from the 
toxicity and/or complications from the intervention prior to starting therapy. 
23.
Criterion modified per Amendment 3
23.1 Phase 1b erdafitinib + cetrelimab cohort and Phase 2: not applicable.

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responsible medical monitor including the final decision must be documented and retained in the 
sponsor’s trial master file and in the investigator’s study files.
If a ≥Grade 3 AE is not attributable to study treatment (erdafitinib or cetrelimab), or the disease 
under study, then all study drugs should be held. If the event resolves to Grade 1 or baseline within 
4 weeks, erdafitinib may be reintroduced at one dose level lower. If the same toxicity does not 
recur or worsen within 4 weeks after re-starting erdafitinib, then cetrelimab may be reintroduced 
at the same dose. Following re-introduction of both study drugs, if the same AE recurs at ≥Grade 
3 or there is a second incidence of a ≥Grade 3 event that is not attributable to erdafitinib, cetrelimab 
or the disease under study, both study drugs should be discontinued.
Guidance for the management of toxicity associated with erdafitinib or cetrelimab, is provided in 
Sections 6.2 and 6.3, respectively.
For more information regarding the following sections, please refer to the 
main body of the protocol.
Page #
Section 6.2 Administration of Erdafitinib
Page 80
Section 6.3 Administration of Cetrelimab
Page 91
Section 6.4 Administration of Platinum Chemotherapy
Page 101
Section 6.5 Toxicity Due to One Study Drug and Continuation of Treatment
Page 101
Section 7 Treatment Compliance
Page 101
Section 8 Concomitant Therapy
Page 102
Section 9 Study Evaluations
Page 105
Section 9.1 Study Procedures
Page 105
Section 9.2 Efficacy Evaluations
Page 108
Section 9.3 Pharmacokinetics and Immunogenicity
Page 110
Section 9.4 Pharmacodynamic Evaluations
Page 111
Section 9.5 Predictive and Exploratory Biomarkers
Page 111
Section 9.6 Safety Evaluations
Page 113
Section 9.7 Sample Collection and Handling
Page 117
Section 10 Subject Completion/Discontinuation of Study 
Treatment/Withdrawal From the Study
Page 117

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Section 11 Statistical Methods
Page 118
Section 12 Adverse Event Reporting
Page 123
Section 13 Product Quality Complaint Handling
Page 130
Section 14 Study Drug Information
Page 130
Section 15 Study-Specific Materials
Page 133
Section 16 Ethical Aspects
Page 133
Section 17 Administration Requirements
Page 138