Conditions: Castration-Resistant Prostate Carcinoma Double-Negative Prostate Carcinoma Metastatic Prostate Carcinoma Prostate Adenocarcinoma Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8
Keywords: Prostate
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
This phase II trial studies how well erdafitinib in combination with abiraterone acetate or enzalutamide works in treating patients with double negative prostate cancer. Erdafitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Testosterone can cause the growth of prostate cancer cells. Abiraterone acetate lowers the amount of testosterone made by the body. This may help stop the growth of tumor cells that need testosterone to grow. Enzalutamide blocks the use of testosterone by the tumor cells. Giving erdafitinib with abiraterone acetate or enzalutamide may work better in treating patients with prostate cancer compared to abiraterone acetate or enzalutamide alone.

Detailed description:
OUTLINE: Patients receive abiraterone acetate orally (PO) once daily (QD) or enzalutamide PO QD on days 1-21. Patients also receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Arms:
arm 1: Patients receive abiraterone acetate orally PO QD or enzalutamide PO QD on days 1-21. Patients also receive erdafitinib PO QD on days 1-21. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.

Interventions: intervention 1: Abiraterone Acetate intervention 2: Enzalutamide intervention 3: Erdafitinib
Intervention descriptions: intervention 1: Given PO intervention 2: Given PO intervention 3: Given PO

Protocol document:
Prot_SAP_000.pdf: 
 
 
Official Title: 
Erdafitinib plus Abiraterone Acetate or Enzalutamide in 
Double Negative Prostate Cancer 
NCT Number: 
NCT03999515 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
10/17/2022 
 
 


PI: Michael T. Schweizer
Protocol Version: 6.0 
1 
Version Date: 17 September 2020 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Clinical Protocol 
Erdafitinib plus Abiraterone Acetate or Enzalutamide in Double Negative Prostate Cancer 
Protocol Version 6.0  
 Protocol: RG1005038 (CC10288) 
Date: August 26, 2022 
Sponsor-Investigator / PI: Michael T. Schweizer 
University of Washington / Fred Hutchinson Cancer 
Center 
Email: schweize@uw.edu 
JNJ-42756493  Erdafitinib 
Drug and Funding Support: Janssen Research & Development * 
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity providing drug and funding support for Janssen Research & 
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; 
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Sciences Ireland UC; or 
Janssen Research & Development, LLC. 
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR 
Part 312). 
Status: 
Approved 
Date: 
26 August 2022 
Prepared by:   Michael T. Schweizer 
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. 
IRO REC'D 10/10/2022
FHCRC IRB Approval  
10/17/2022 
Document Released Date


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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Version Date: 17 September 2020 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
 
 
 
 
TABLE OF CONTENTS 
TIME AND EVENTS SCHEDULE............................................................................................................... 10 
ABBREVIATIONS ...................................................................................................................................... 12 
1. 
INTRODUCTION................................................................................................................................ 14 
1.1. 
Background .................................................................................................................................... 14 
1.2. 
Double Negative Prostate Cancer ................................................................................................. 15 
1.3. 
Fibroblast Growth Factor Receptors and Erdafitinib ...................................................................... 19 
1.3.1. 
Fibroblast Growth Factor Receptors ........................................................................................... 19 
1.3.2. 
Erdafitinib .................................................................................................................................... 20 
1.3.2.1. 
Erdafitinib Efficacy ................................................................................................................... 20 
1.3.2.2. 
Erdafitinib Safety...................................................................................................................... 21 
1.4. 
Enzalutamide ................................................................................................................................. 22 
Refer to Enzalutamide’s FDA label for additional pharmacology and clinical data. .............................................. 23 
1.5. 
Abiraterone Acetate ....................................................................................................................... 24 
1.6. 
Overall Rationale for the Study ...................................................................................................... 28 
2. 
OBJECTIVE AND ENDPOINTS ........................................................................................................ 28 
2.1. 
Primary Objective ........................................................................................................................... 28 
2.2. 
Secondary Objectives .................................................................................................................... 29 
2.3. 
Planned Exploratory Objectives ..................................................................................................... 29 
3. 
STUDY DESIGN AND RATIONALE ................................................................................................. 29 
4. 
SUBJECT POPULATION .................................................................................................................. 31 
4.1. 
Inclusion Criteria ............................................................................................................................ 31 
4.2. 
Exclusion Criteria ........................................................................................................................... 32 
5. 
TREATMENT ALLOCATION AND BLINDING ................................................................................. 34 
6. 
DOSAGE AND ADMINISTRATION .................................................................................................. 34 
6.1. 
Erdafitinib ....................................................................................................................................... 34 
6.1.1. 
Dose Modifications and Dose Delays for Erdafitinib ................................................................... 35 
6.1.2. 
Guidance for Specific Erdafitinib Toxicities ................................................................................. 37 
6.1.2.1. 
Grading of Hyperphosphatemia and Nail Disorders ................................................................ 37 
6.1.2.2. 
Guidelines for the Management of Elevated Phosphate Levels .............................................. 37 
6.1.2.3. 
Guidelines for the Management of Dry Mouth and Stomatitis ................................................. 38 
6.1.2.4. 
Guidelines for the Management of Dry Skin and Skin Toxicity ................................................ 39 
6.1.2.5. 
Guidelines for Management of Nail Toxicity (Onycholysis, Onychodystrophy, and    
Paronychia).............................................................................................................................. 40 
6.1.2.6. 
Guidelines for Eye Toxicity Associated With Vision Changes ................................................. 42 
6.1.2.7. 
Guidelines for the Management of Dry Eye ............................................................................. 44 
6.2. 
Enzalutamide ................................................................................................................................. 44 
6.2.1. 
Dose Modifications ...................................................................................................................... 44 
6.3. 
Abiraterone Acetate ....................................................................................................................... 44 
6.3.1. 
Dose Modifications for LFT Abnormalities Attributed to Abiraterone Acetate .................................... 45 
6.3.2. 
Dose Modifications for Hypokalemia Attributed to Abiraterone Acetate ............................................. 45 
6.3.3. 
Dose Modifications for Hypertension and Edema/Fluid Retention Attributed to Abiraterone 
Acetate ......................................................................................................................................... 46 
7. 
TREATMENT COMPLIANCE ............................................................................................................ 46 
8. 
CONCOMITANT THERAPY .............................................................................................................. 46 
8.1. 
Permitted Medications .................................................................................................................... 47 


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8.2. 
Prohibited Medications ................................................................................................................... 47 
8.3. 
Precautions for Concomitant Medications ...................................................................................... 48 
9. 
STUDY EVALUATIONS .................................................................................................................... 49 
9.1. 
Study Procedures ........................................................................................................................... 49 
9.1.1. 
Overview ..................................................................................................................................... 49 
9.1.2. 
Screening Phase ......................................................................................................................... 50 
9.1.3. 
Treatment Phase ........................................................................................................................ 50 
9.1.4. 
End of Treatment ........................................................................................................................ 51 
9.2. 
Efficacy Evaluations ....................................................................................................................... 51 
9.2.1. 
Evaluations ................................................................................................................................. 52 
9.2.1.1. 
Pathologic Assessment ........................................................................................................... 52 
9.2.1.2. 
RECIST Assessment of Disease ............................................................................................. 53 
9.2.1.3. 
Radiographic Images Assessment .......................................................................................... 53 
9.3. 
Correlative research ....................................................................................................................... 53 
9.4. 
Safety Evaluations ......................................................................................................................... 54 
9.4.1. 
Adverse Events ........................................................................................................................... 54 
9.4.2. 
Clinical Laboratory Tests ............................................................................................................ 54 
9.4.3. 
Renal Toxicity Evaluation ........................................................................................................... 55 
9.4.4. 
Electrocardiogram ....................................................................................................................... 55 
9.4.5. 
Ophthalmic Examination ............................................................................................................. 55 
9.4.6. 
Vital Signs ................................................................................................................................... 56 
9.4.7. 
Physical Examination .................................................................................................................. 56 
9.4.8. 
ECOG Performance Status ........................................................................................................ 56 
9.5. 
Sample Collection and Handling .................................................................................................... 56 
10. 
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 56 
10.1. 
Completion ..................................................................................................................................... 56 
10.2. 
Discontinuation of Study Treatment/Withdrawal from the Study.................................................... 57 
10.3. 
Withdrawal From the Use of Research Samples ........................................................................... 58 
11. 
DATA MONITORING AND ADVERSE EVENT REPORTING .......................................................... 58 
11.1. 
Management of Safety Data .......................................................................................................... 59 
11.2. 
Definitions ....................................................................................................................................... 59 
11.3. 
Pregnancy ...................................................................................................................................... 63 
11.4. 
Adverse Event Monitoring and Reporting ...................................................................................... 63 
11.5. 
Procedures for Reporting Safety and Data and Product Quality Complaints (PQCs) for 
J&J Medicinal Products to the Company ....................................................................................... 64 
11.5.1. 
Serious Adverse Events (SAE), Adverse Events of Special Interest, and Special Reporting 
Situations  ................................................................................................................................. 64 
11.5.2. 
Product Quality Complaints Reporting........................................................................................ 65 
11.6. 
Evaluating Adverse Events............................................................................................................. 66 
11.6.2. 
Maintenance of Safety Information ............................................................................................. 68 
11.6.3. 
SAEs Listing ................................................................................................................................ 68 
11.7. 
IRB Reporting ................................................................................................................................. 68 
11.8. 
Protocol Amendments .................................................................................................................... 69 
11.9. 
Informed Consent ........................................................................................................................... 69 
12. 
STATISTICAL METHODS................................................................................................................. 69 
12.1. 
Subject Information ........................................................................................................................ 69 
12.2. 
Sample Size Determination ............................................................................................................ 69 
12.3. 
Efficacy Analyses ........................................................................................................................... 70 
12.4. 
Correlative Research Analyses ...................................................................................................... 70 
REFERENCES ............................................................................................................................................ 71 
Appendix 2: Common Terminology Criteria for Adverse Events V5.0 (CTCAE) ......................................... 75 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
 
 
Erdafitinib plus Abiraterone Acetate or Enzalutamide in Double Negative Prostate Cancer 
 
Background 
 
Many of the treatments for metastatic castration-resistant prostate cancer (mCRPC) are 
directed at suppressing the androgen receptor (AR)-signaling axis. While AR-directed 
therapies are initially effective, resistance inevitability occurs. The continued lethality of this 
disease underscores the importance of testing therapeutics aimed at alternate pathways. 
Mechanistic studies have revealed that MAPK-signaling, which is activated by FGF/FGFR 
signaling, is an important AR bypass mechanism in men with late stage, double negative 
prostate cancer (DNPC). Importantly, targeting FGF/FGFR-signaling with pan-FGFR 
inhibitors results in significant tumor growth inhibition in both engineered LNCaPAPIPC cells 
and DNPC LuCaP 173.2 PDX models1. It is important to note that unlike other malignancies 
(e.g. bladder and lung cancer), patients with a DNPC phenotype usually do not harbor genomic 
alterations in FGFR, and over-activation of FGF/FGFR-signaling is primarily driven by 
autocrine/paracrine activation of this pathway. In total, this data demonstrates that 
FGF/FGFR-signaling is a critical driver of late stage CRPC, and supports testing FGFR 
inhibitors in DNPC patients. 
 
On this basis, we are launching a phase II trial testing the pan-FGFR inhibitor erdafitinib in men 
with metastatic CRPC who have previously progressed on either abiraterone acetate or 
enzalutamide and who have exhibited a DNPC phenotype on biopsy. Patients will continue on 
the most recent next- generation AR-directed therapy they progressed on (i.e. either abiraterone 
acetate or enzalutamide) in order to maintain suppression of AR-signaling, and erdafitinib will 
be added to their regimen. Erdafitinib will be dosed at the recommended Phase II dose, and 
abiraterone acetate or enzalutamide will be administered at their respective FDA approved dose. 
Study subjects will continue on erdafitinib plus either abiraterone acetate or enzalutamide until 
radiographic progression or intolerable toxicity. We hypothesize that erdafitinib in combination 
with a next-generation AR-directed therapy will show clinical efficacy in men with mCRPC with 
a DNPC phenotype who have progressed on abiraterone acetate or enzalutamide 
 
Objectives 
 
Primary Objective: To determine the objective tumor response rate in subjects with measurable 
lesions as defined by RECIST v1.1 criteria in mCRPC patients with a DNPC molecular 
phenotype receiving either enzalutamide or abiraterone acetate in combination with erdafitinib. 
 
Secondary Objectives 
 
1. Determine the radiographic PFS in patients using RECIST 1.1 criteria for soft 
tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for 
bone metastases2,3 
2. Determine the time to response using RECIST 1.1 criteria2 
3. Determine the overall survival defined as the time interval from C1D1 to the date 
of death 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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4. PSA response, defined as >50% reduction in PSA compared with baseline at any 
point during treatment 
5. Assess the incidence and severity of adverse events according to National Cancer 
Institute- Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 
 
Planned Exploratory Objectives 
 
Correlative work will be performed in order to determine biomarkers predictive of response to 
combination therapy. Examples of correlative work may include, but will not be limited to: 
 
1. Immunohistochemistry (IHC) for phosphorylated FGFR and FGFR substrate 2 (FRS2) 
in tumor tissue 
2. IHC for PSA and AR expression in tumor tissue 
3. Tumor tissue transcript profiling studies to assess candidate biomarkers for 
response/resistance to FGFR inhibitor therapy and to evaluate core signaling program 
for FGF/FGFR, MAPK, and AR. 
4. Next-generation sequencing of pre-treatment tumor biopsies and cell-free 
circulating tumor DNA (ctDNA) to identify genomic alterations correlating with 
response or resistance to treatment, and confirm FGFR alteration status 
5. Serial blood (baseline, 12-weeks, progression) will be obtained in order to develop 
a blood-based gene expression response signature 
6. Serum FGF ligand levels (FGF8, FGF9, FGF19) will be drawn at baseline, 12-weeks 
and at progression 
 
Study Design 
This will be a phase II trial testing the pan-FGFR inhibitor, erdafitinib, in men with metastatic 
CRPC who have progressed on either abiraterone acetate or enzalutamide (Fig 6). Eligible patients 
must have CRPC (defined as disease progression in spite of a castrate serum testosterone [≤50 
ng/dl]), and evidence of RECIST evaluable disease to enroll2. Given that the patient population 
of interest will be heavily pre-treated, and likely enriched for both small cell/NE and double 
negative prostate cancer, it is recommended that patients undergo a baseline metastatic biopsy 
prior to enrolling to rule out predominate small cell/NE variant prostate cancer. Patients with DNPC 
defined by IHC criteria will be eligible to enroll (see Section 9.2.1.1). Transcript profiling 
methods for identifying DNPC may also be accepted for determining trial eligibility at the PI’s 
discretion. This is based on data showing that transcriptional signatures can accurately define 
the various prostate cancer subtypes, including DNPC4,5. Eligible patients must have 
demonstrated evidence of active progression per Prostate Cancer Working Group 3 (PCWG3) 
criteria while on enzalutamide or abiraterone acetate at any time prior to enrollment3. If not 
surgically castrated, participants must be maintained on an LHRH analogue (e.g. leuprolide, 
goserelin) 
Eligible patients will continue on the next-generation AR-directed therapy they most recently 
progressed on (i.e. either abiraterone acetate or enzalutamide) in order to maintain suppression 
of AR-signaling, and erdafitinib will be added to their regimen. If a trial subject is not 
currently on abiraterone or enzalutamide at the time of screening, they must restart the AR-


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
 
 
directed therapy most recently received and demonstrate two successive PSA rises or other 
evidence of progression prior to starting treatment per protocol. Erdafitinib will be 
administered at 8 mg once daily orally, with pharmacodynamic uptitration to 9 mg if serum 
phosphate was below 5.5mg/dL in absence of significant toxicity on cycle 1 day 14 (see 
Section 6.1). 
Abiraterone acetate or enzalutamide will be administered at their respective FDA approved dose 
(i.e. abiraterone acetate 1000 mg PO daily; enzalutamide 160 mg PO daily). Subjects continuing 
on abiraterone acetate will also be required to receive prednisone 5 mg PO twice daily in order 
to blunt mineralocorticoid symptoms associated with abiraterone acetate. Study subjects will 
continue on erdafitinib plus either abiraterone acetate or enzalutamide until radiographic 
progression, intolerable toxicity or two-years of treatment, whichever comes first. 
 
Study Schema 
 
 
 
Eligibility 
 
Inclusion Criteria: 
 
1. Patients must be > 18 years of age prior to signing informed consent 
 
2. History of histologically diagnosed prostatic adenocarcinoma 
 
3. Participants must have evidence of castration resistant prostate cancer as evidenced by a 
confirmed rising PSA or radiographic progression (per Prostate Cancer Working Group 3 
[PCWG3] criteria) and a castrate serum testosterone level (i.e. < 50 ng/dL)3 
 
4. Participants must have previously progressed on abiraterone acetate and/or enzalutamide, 
with PSA or radiographic progression on the most recent agent per PCWG3 criteria. If 
the most recent agent received was abiraterone or enzalutamide, there should be no 
washout prior to initiating erdafitinib per protocol3 
 
5. Measurable disease as defined per RECIST v1.1 criteria2 
 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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FGFR Inhibition in DNPC 
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6. Subjects who have progressed on only one next-generation AR-directed therapy (e.g. 
abiraterone, enzalutamide) and who have not received taxane chemotherapy will be 
required to have evidence of double-negative prostate cancer as defined by 
immunohistochemistry (see Section 9.2.1.1) on biopsy. A fresh metastatic biopsy within 
8 weeks is preferred; however, any archival tissue showing a DNPC phenotype will be 
acceptable for determining eligibility. Patients who have received two prior lines of AR-
directed therapy and at least one prior taxane do not require histologic confirmation of 
DNPC. Note: transcript profiling methods for defining DNPC may be accepted per the 
PI’s discretion 
 
7. ECOG performance status score <2 
 
8. Clinical and laboratory values and cardiovascular measurements at screening: 
 
Hematology 
Hemoglobin 
> 8  g/dL (>5 mmol/L) (must be without 
red blood cell [RBC] transfusion within 7 
days prior to the laboratory test) 
Platelets 
> 75 x 109/L 
Absolute Neutrophil Count (ANC) 
> 1.5 x 109/L (prior growth factor support 
is permitted but must be without support in 
the 7 days prior to the laboratory test) 
Chemistry 
AST and ALT 
< 2.5 x upper limit of normal (ULN) or < 5 
x ULN for subjects with liver metastases 
Creatinine clearance 
>40 mL/min/1.73 m2 based upon Modified 
Diet in Renal Disease formula calculation 
Total bilirubin 
< 1.5 x ULN; except in subjects with 
congenital bilirubinemia, such as Gilbert’s 
syndrome 
Cardiovascular 
Corrected QT interal (QTcF or QTcB) 
<480 msec based on the average of 
triplicate assessments performed 
approximately 5 minutes apart 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; GFR = glomerular filtration rate; QTcB = QT corrected interval by the 
Bazett’s formula; QTcF = QT corrected interval by the Fridericia’s formula; ULN = 
upper limit of normal 
IF Glibert’s disease is present, direct bilirubin can be measured 
 
9. Subjects must agree to use acceptable contraception (see Section 11.3 for requirements) 
 
10. Must sign an informed consent form (ICF) indicated that he or she understands the 
purpose of, and procedures required for, the study and is willing to participate in the 
study 
 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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FGFR Inhibition in DNPC 
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Exclusion Criteria 
 
1. Treatment with any other investigational agent or participation in another clinical trial 
with therapeutic intent within 14 days prior to enrollment 
 
2. Active malignancies (i.e. requiring treatment change in the last 24 months) other than 
malignancy under study (except skin cancers within the last 24 months that are 
considered completely cured) 
 
3. Evidence of predominant small cell or neuroendocrine variant prostate cancer (see 
section 9.2.1.1) on most recent standard of care metastatic biopsy 
 
4. Symptomatic central nervous system (CNS) metastases. Treated CNS metastases will be 
allowed if these are stable for at least 8 weeks prior to enrollment 
 
5. Received prior FGFR inhibitor treatment or if the subject as known allergies, 
hypersensitivity, or intolerance to erdafitinib or its excipients 
 
6. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any 
grade 
 
7. Has persistent phosphate level >ULN during screening (on 2 consecutive assessments at 
least 1 week apart, within 14 days of treatment and prior to Cycle 1 Day 1) and despite 
medical management 
 
8. Has a history of current uncontrolled cardiovascular disease including: 
 
a. Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de 
Pointes, cardiac arrest, or known congestive heart failure Class III-V within the 
preceding 3 months; cerebrovascular accident or transient ischemic attack within 
the preceding 3 months 
 
b. Pulmonary embolism or other VTE (venous thromboembolism) within the 
preceding 2 months 
 
9. Has known active AIDS (human immunodeficiency virus (HIV) infection) 
 
10. Hepatitis B infection as defined according to the American Society of Clinical Oncology 
guidelines. In the event the infection status is unclear, quantitative levels are necessary to 
determine the infection status. Hepatitis C (anti-hepatitis C virus [HCV] antibody positive 
or HCV-RNA quantitation positive) or known to have a history of hepatitis C. If positive, 
further testing of quantitative levels to rule out positivity is required 
 
11. Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities 
which are not clinically significant such as alopecia, skin discoloration, hot flashes, 
Grade 1 neuropathy, Grade 1-2 hearing loss) 


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12. Has impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, 
known gastric ulcers, or unhealed incisions 
 
13. Major surgery within 2 weeks of the first dose, or will not have fully recovered from 
surgery, 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) 
 
14. Any serious underlying medical conditions, such as: 
a. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal 
infection 
b. Active autoimmune or a documented history of autoimmune disease 
 
Statistical Considerations 
Sample Size Justification 
Although there are no published data on ORR among patients with progressive disease on both 
abiraterone acetate and enzalutamide, several small studies have explored the objective 
response rates of abiraterone acetate following enzalutamide and vice versa in the post-
docetaxel setting: with ORRs ranging from 3-8%6,7. Therefore, if we assume a historical-
control ORR (H0) of 5% and an alternative hypothesis of a 25% ORR (H1), a sample size of 
23 patients gives 86% power to detect a difference in ORR of the hypothesized magnitudes 
with a type-1 error of 3% based on an exact binomial test. We will therefore plan to enroll up 
to 25 patients to account for 10% dropout. 
 
Analysis Plan 
The primary objective will be to determine the ORR, which will be calculated as the 
percentage of patients, with 95% confidence intervals, achieving a complete response (CR) or 
partial response (PR) across the entire study population at any time. On the basis of an exact 
binomial test, 4 responses are needed to reject the null hypothesized 5% historical control 
ORR in favor of the alternative at a significance level of p=0.026. Secondary objectives will 
include determining: radiographic progression free survival (PFS) in patients using RECIST 
1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria 
for bone metastases; time to response using RECIST 1.1 criteria; overall survival (OS) 
defined as the time interval from C1D1 to the date of death; PSA response, defined as >50% 
reduction in PSA compared with baseline at any point during treatment; and the incidence and 
severity of adverse events according to National Cancer Institute-Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.02,3. Survival endpoints (e.g. PFS, OS) will 
be presented with Kaplan-Meier curves, and the median survival with 95% CI will be 
calculated. Rates will be reported as percentages with 95% CI. We will characterize AEs by 
type and grade. Safety will be summarized as the severity and frequency of a given AE. 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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TIME AND EVENTS SCHEDULE 
 
Pre- 
Screeninge 
Screening 
Treatment Cycles 
End of 
Treatment 
Treatment Cycle 
Pre- 
Screeninge 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 
4 
After 
Cycle 4 
Discontinue 
Cycle Day 
Day -56 to 
0 
Day -30 to 
0 
Day 1 ± 7 
daysf 
Day 14 ± 
2 days 
Day 1 ± 7 
days 
Within 14 
daysg 
Administrative 
Procedures 
Informed Consent 
X 
Inclusion/Exclusion 
Criteria 
X 
Demographics and 
Medical History 
X 
Prior and Concomitant 
Medication Review 
X 
X 
X 
X 
X 
Q1C 
X 
Erdafitinib 
Dispensation 
X 
X 
X 
X 
Q1C 
Clinical Assessments 
Review Adverse 
Events 
X 
X 
X 
X 
Q1C 
X 
ECOG Performance 
Status 
X 
X 
X 
X 
X 
Q1C 
X 
Vital Signs and 
Weight 
X 
X 
X 
X 
X 
Q1C 
X 
Ophthalmic exam 
X 
Physical Examinationa 
X 
X 
X 
X 
X 
Q1C 
X 
EKG 
X 
Laboratory 
Assessments 
PSA 
X 
X 
Q3C 
X 
Testosterone Level 
X 


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Pre- 
Screeninge 
Screening 
Treatment Cycles 
End of 
Treatment 
Treatment Cycle 
Pre- 
Screeninge 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 
4 
After 
Cycle 4 
Discontinue 
Cycle Day 
Day -56 to 
0 
Day -30 to 
0 
Day 1 ± 7 
daysf 
Day 14 ± 
2 days 
Day 1 ± 7 
days 
Within 14 
daysg 
Phosphate Level 
X 
X 
X 
X 
X 
X 
Q1C 
X 
CBC with Differential 
X 
X 
X 
X 
X 
X 
Q1C 
X 
Comprehensive Serum 
Chemistry Panel 
X 
X 
X 
X 
X 
Q1C 
X 
PT/INR and PTT 
X 
X 
Correlative Studies 
Blood Collectionb 
X 
X 
X 
Research biopsy 
X 
Xh 
Pathologic evaluationc 
X 
X 
Radiographic 
assessmentsd 
X 
X 
Q3C 
Xi 
a. 
Full physical exam is required at screening. Subsequent physical exams may be targeted. 
b. 
Refer to Laboratory Manual for details on correlative blood sample processing. 
c. 
Pathologic assessment of a biopsy demonstrating DNPC at any point in the patient’s treatment history is a pre-screening requirement. 
However, a fresh biopsy within 8 weeks of enrollment is recommended to rule out predominate small cell/NE variant prostate cancer. 
Research biopsy will only occur if considered safe by the treatment team. 
d. 
Radiographic assessments should include a CT chest/abdomen/pelvis and bone scan. 
e. 
If archival metastatic tissue previously obtained  is already available and suitable for pathologic evaluation, another 
metastatic biopsy will not be mandated. CBC with Differential, PT/INR and PTT will only be obtained if metastatic biopsy 
is planned. 
f. 
Assessments done during the screening period do not need to be repeated if within 7 days. 
g. 
Assessments do not need to be repeated if within 7 days. 
h. 
Research biopsy will be performed only if feasible (i.e. safe and metastatic lesion amenable to biopsy is present). 
i. 
Radiographic assessments do not need to be repeated if within 8 weeks. 
 
 
 
 


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ADT 
Androgen Deprivation Therapy 
AE 
Adverse Event 
ANC 
Absolute Neutrophil Count 
aPTT 
Activated Partial Thromboplastin Time 
AR 
Androgen Receptor 
AR-V 
Androgen Receptor Splice Variant 
ARFL 
Full Length Androgen Receptor 
ARV7 
Androgen Receptor Splice Variant 7 
BID 
Twice Daily 
CR 
Complete Response 
CRPC 
Castration-Resistant Prostate Cancer 
CTC 
Circulating Tumor Cell 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
Cell-Free Circulating Tumor DNA 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
FFPE 
Formalin-Fixed Paraffin Embedded 
FHCRC 
Fred Hutchinson Cancer Research Center 
HSPC 
Hormone-sensitive Prostate Cancer 
IF 
Immunofluorescence 
IHC 
Immunohistochemistry 
INR 
International Normalized Ratio 
IV 
Intravenous 
LHRH 
Luteinizing Hormone-Releasing Hormone 
mCRPC 
Metastatic Castration-Resistant Prostate Cancer 
NCI 
National Cancer Institute 
OTC 
Over-The-Counter 
PC 
Prostate Cancer 
PCWG 
Prostate Cancer Working Group 
PD 
Progressive Disease 
PD 
Pharmacodynamic 
PDX 
Patient Derived Xenograft 
PK 
Pharmacokinetic 
PO 
By Mouth 
PR 
Partial Response 
PSA 
Prostate Specific Antigen 
PSA50 
50% Decline in PSA from Baseline 
PT 
Prothrombin Time 
Q1C 
Every 1 Cycle 


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Q3C 
Every 3 Cycles 
Q3W 
Every 3 weeks 
qPCR 
Quantitative Real-Time PCR 
RNA-Seq 
RNA Sequencing 
SD 
Stable Disease 
T 
Testosterone 
ULN 
Upper Limit of Normal 
UW 
University of Washington 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. 
INTRODUCTION 
 
1.1. 
Background 
Prostate cancer is the second leading cause of cancer death among American men8. It is primarily 
an androgen driven malignancy, with treatment of metastatic disease aimed at removing 
androgen stimulus. Since the 1940s, the backbone of treatment for men with newly diagnosed 
advanced prostate cancer has entailed either surgical or medical castration (i.e. androgen 
deprivation therapy; ADT). While ADT is initially highly effective in men with metastatic 
prostate cancer, resistance invariably develops, with disease progression despite castrate levels of 
serum testosterone (i.e. ≤50 ng/dL) signifying the emergence of a disease state known as 
castration resistant prostate cancer (CRPC). 
 
Metastatic CRPC (mCRPC) remains a fatal disease despite six treatments approved by the FDA 
since 2004, which have been shown to extend survival9-17. The first of these agents to be 
approved was docetaxel, a semisynthetic taxane which inhibits microtubule synthesis. The 
landmark TAK-327 and SWOG-9916 trials reported that docetaxel had an overall survival 
benefit in mCRPC when compared to mitoxantrone14,17. Since then, a second taxane, cabazitaxel 
has been shown to have a survival benefit in men with mCRPC who had progressed after 
docetaxel treatment and was approved for use in this setting11. There has also been a 
radiopharmaceutical and an immunotherapeutic agent which have gained approval for mCRPC. 
Radium-223 is an alpha emitting calcium mimetic which prolongs survival in men with mCRPC 
that is predominately metastatic to the bones13. Sipuleucel-T is an immunotherapy in which 
autologous peripheral blood monocytes (PBMCs) are activated by a recombinant fusion protein 
consisting of the prostate antigen prostatic acid phosphatase fused to granulocyte-macrophage 
colony-stimulating factor12. 
 
The observation that AR regulated genes (e.g. PSA) remain expressed in a castrate state led to 
the further exploration of the AR-signaling axis as a therapeutic target in men with mCRPC and 
have resulted in the development of effective new AR-directed agents like abiraterone acetate 
and enzalutamide. Both of these drugs inhibit AR-signaling in men with mCRPC through 
disrupting the ligand-AR interaction (abiraterone acetate through ligand depletion and 
enzalutamide through receptor antagonism)9,10,15 These agents are unfortunately not curative, 
however, and resistance typically occurs within 1-2 years. In addition, given the considerable 
mechanistic overlap between abiraterone acetate and enzalutamide, it is not surprising that 
clinical evidence of cross-resistance between these agents has begun to emerge6,7 Recent work 
by our group has shown that in the face of chronic AR-signaling inhibition, a subset of these 
patients will develop androgen pathway-independent prostate cancer (APIPC) – a molecular 
prostate cancer subset defined by no AR-signaling activity and the absence of neuroendocrine 
features (i.e. double negative prostate cancer; DNPC)1. 
 
Mechanistic studies have revealed that MAPK-signaling, which is activated by the fibroblast 
growth factor (FGF)/FGF receptor (FGFR) pathway, is an important AR bypass mechanism in 
men with DNPC. Importantly, targeting FGF/FGFR-signaling with pan-FGFR inhibitors results 
in significant tumor growth inhibition in both engineered APIPC cells and DNPC patient derived 
xenograft (PDX) models1. In contrast to other malignancies (e.g. bladder and lung cancer), 
patients with DNPC usually do not harbor genomic alterations in FGFR, and over-activation of 


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FGF/FGFR-signaling is primarily driven by autocrine/paracrine activation of this pathway. In 
total, this data demonstrates that FGF/FGFR-signaling is a critical driver of late stage mCRPC 
and supports our hypothesis that the pan-FGFR inhibitor erdafitinib in combination with 
abiraterone acetate or enzalutamide will be effective in men with multi-drug resistance mCRPC. 
 
1.2. 
Double Negative Prostate Cancer 
Despite multiple effective therapies, mCRPC remains an invariably fatal disease with resistance 
to currently available therapies occurring in 1-2 years in most cases. Various pathways to 
resistance have been described, many of which still rely on the androgen axis18.  Recent work, 
however, has demonstrated that a subset of these cancers become completely independent of AR- 
signaling, without expressing classic neuroendocrine (NE) or small cell markers (e.g. 
synaptophysin) – a disease state herein referred to as double negative prostate cancer (DNPC) or 
androgen pathway independent prostate cancer (APIPC). Additional work has shown that DNPC, 
as well as other prostate cancer subtypes (e.g. AR+/NE-, AR-/NE+ and AR+/NE+) are 
associated with reproducible transcriptional profiles, which accurately define these molecular 
subtypes4,5. The emergence of DNPCs has become more prevalent with the widespread use of 
the next-generation AR-signaling inhibitors abiraterone acetate and enzalutamide. As an 
example, there has been a shift toward more tumors demonstrating a DNPC phenotype following 
the approval of abiraterone acetate in 2011 compared to the pre-abiraterone acetate era, and data 
from our rapid autopsy program has shown that 23.3% of mCRPC patients will die with DNPC 
compared to only 5% prior to 20111. 
 
 
Figure 1. The incidence of AR-null/NE-null prostate cancers has increased since approval of abiraterone acetate in 
2011. 
 
Given that nearly 1/4 mCRPC patients will die of DNPC – a clinical state with no proven 
therapies – new therapeutic approaches for these men are sorely needed. In order to study the 
molecular drivers of DNPC, our group created an AR-null/NE-null engineered cell-line model 
from parental LNCaP cells (Fig 2)1. LNCaP prostate cancer cells were transduced with an 


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inducible anti-AR short hairpin RNA (shRNA) as well as an androgen response element-driven 
suicide gene (LNCaPshAR/pATK). LNCaPshAR/pATK cells were then subjected to increasingly severe 
AR pathway suppression. After 2 weeks of androgen deprivation in charcoal stripped 
serum(CSS), medium was supplemented with 1 mg/mL doxycycline (Dox) to induce the anti-AR 
shRNA, which produced >99% cell death. After 5 months, a residual population of viable cells 
remained. This colony was treated with a 2-week course of ganciclovir to eliminate cells 
expressing functional AR. Surviving cells were designated LNCaP-AR Program-Independent 
Prostate Cancer (LNCaPAPIPC). 
 
 
Figure 2. Development of a cellular model of APIPC. LNCaP cells with a doxycycline (Dox)-inducible shRNA 
targeting the AR (shAR) and an androgen-driven thymidine kinase gene (pATK) were depleted of androgens using 
ADT then treated with Dox to induce the AR-directed shRNA, then treated with ganciclovir to eliminate cells with 
AR-driven thymidine kinase expression. 
 
AR and PSA were nearly undetectable in LNCaPAPIPC and transcripts comprising an AR activity 
signature were substantially decreased compared to the parental cell line (Fig 3A). Likewise, 
there was no AR or PSA protein expression in LNCaPAPIPC grown in vivo as subcutaneous 
xenografts24. Importantly, NE-associated genes were not upregulated in LNCaPAPIPC cells grown 
with or without androgen supplementation (Fig 3B). Furthermore, LNCaPshAR/pATK and 
LNCaPAPIPC grown as murine xenografts do not express the NE markers chromogranin or 
synaptophysin.  Studies examining the drivers of LNCaPAPIPC cell growth found that an autocrine 
FGF signaling program is likely activated in LNCaPAPIPC in the absence of AR to maintain cell 
survival and growth via MAPK (Fig 3C and D). Importantly, RNA-seq data from our rapid 
autopsy program demonstrates that DNPC patients have a similar transcriptional program to our 
LNCaPAPIPC model, with overexpression of FGF ligands, FGF receptors and genes comprising 
the MEK/ERK activity signature1. 


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Figure 3. LNCaPAPIPC cells demonstrate an AR-null/NE-null transcriptional program, with activation of MAPK 
signaling and overexpression of FGF8. A. LNCaPAPIPC demonstrate differential expression of AR regulated genes 
compared to LNCaPshAR/pATK. B. LNCaPAPIPC dp not demonstrate expression of NE prostate cancer genes. NE- 
LuCaP PDX gene expression is provided for reference. C. Phosphorylated MEK and dually phosphorylated 
ERK1/2 (ppERK1/2) are elevated in LNCaPAPIPC compared with LNCaPshAR/pATK. D. FGF8 is overexpressed in 
LNCaPAPIPC compared to LNCaPshAR/pATK. 


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Figure 4. Expression of FGF ligands, FGF receptors, and genes comprising an MEK/ERK activity signature. 
Relative ratios of RNA-seq transcript abundances are shown, along with mean FPKM values and signature scores 
(AR+/NE , n = 58 tumors from 35 men; AR /NE , n = 9 tumors from 5 men). 
 
To demonstrate that FGF8 was sufficient to promote the growth of cells cultured under total AR 
pathway suppression, we treated parental LNCaPshAR/pATK grown in androgen-deprived 
conditions with Dox to suppress AR expression, and added FGF8b1. FGF8b maintained cell 
proliferation during AR pathway ablation (Fig 5A). Of note, the addition of the FGFR 
antagonist, PD173074, to cells treated with Dox and FGF8 was growth inhibitory. LNCaPAPIPC 
murine xenografts were also inhibited by PD173074 (Fig 5B). We also tested whether FGFR 
inhibition was an effective strategy in a patient derived xenograft (PDX) model of DNPC, the 
LuCaP 173.2 model, and found that treatment with the FGFR antagonist CH-5183284 did indeed 
result in significant growth inhibition (Fig 5C). Finally, we compared the growth inhibitory 
effects of erdafitinib (a potent pan-FGFR inhibitor) vs. CH-5183284 in LNCaPAPIPC cells grown 
in androgen-deprived culture conditions and found that erdafitinib was a more potent inhibitor 
of LNCaPAPIPC growth. These data indicate that pharmacologic inhibition of FGFR activity is 
likely to be effective in men with DNPC. 
 


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Fig 5. FGF signaling can rescue prostate cancer cell growth following AR-signaling ablation and targeting the FGF 
receptor is effective in DNPC models. A. LNCaPshAR/pATK cells were cultured in androgen-depleted medium ±25 
ng/mL FGF8, ±1 mM PD173074 (FGFR inhibitor), and ±1 mg/mL Dox. Solidlines, no Dox; dotted lines, with Dox. 
Cell number was determined using Cyquant, and values were normalized to day 0. Note: Addition of Dox results in 
AR knockdown via an inducible AR shRNA (see Fig 2). B. LNCaPAPIPC cells were inoculated subcutaneously in 
castrate SCID mice receiving Dox-supplemented feed. When tumors reached 200 mm3 in size, treatment was initiated 
with the FGFR antagonist PD173074 or vehicle control. Tumor volumes were measured every 2 days (n = 5). *p < 
0.01. C. LuCaP173.2 tumors were implanted subcutaneously in castrate SCID mice. When tumors reached 200 mm3 
in size, treatment was initiated with the FGFR antagonist CH-5183284 or vehicle control. Tumor volumes were 
measured every 2 days (n = 15). *p < 0.01. D. LNCaPshAR/pATK cells were cultured in androgen-depleted medium with 
either erdafitinib or CH-5183284. Cell growth was significantly (P<0.05) inhibited with erdafitinib compared to CH- 
5183284. 
 
More recent data has broadly implicated a FGFR signaling as a key mediator of lineage plasticity, 
which typically accompanies resistance to AR-signaling inhibitors and occurs increasingly in late 
stage prostate cancer19,20.  This work has shown that erdafitinib may also be able to reprogram 
CRPC toward a more differentiated phenotype.  Indeed, additional unpublished work from our 
group has demonstrated that FGFR inhibition may exert an anti-tumor effect across a variety of 
prostate cancer phenotypes (Figure 6).  These data support using erdafitinib more broadly iin the 
treatment of late stage prostate cancer. In addition, we have observed marked phenotypic 
heterogeneity in men with late stage prostate cancer, indicating that metastatic biopsies targeting a 
single lesion may fail to appreciate lineage plasticity at other sites of disease and/or emergence of 
DNPC phenotypes20-22. 


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Figure 6. Response to FGFRi in LuCaP PDX cells. Tumors were dissociated and then cells were treated for 3-days in 
vitro. Viability was assessed by CellTitre Glo. Neuroendocrine (NEPC), DNPC, AR-low and AR+ PDX cell survival 
data is provided  
 
1.3. 
Fibroblast Growth Factor Receptors and Erdafitinib 
 
1.3.1. 
Fibroblast Growth Factor Receptors 
The family of fibroblast growth factor receptors (FGFRs) consists of four highly conserved 
transmembrane receptors tyrosine kinases, namely FGFR1 to 4 and a 5th receptor, which lacks the 
intracellular kinase domain (FGFR5, also known as FGFRL1). Together, these receptors are able 
to bind to over 20 different fibroblast growth factor (FGF) ligands. FGFR signaling has been 
shown to be enhanced by genetic alterations such as gene amplification, mutation or chromosomal 
translocation, thereby affecting various cellular mechanisms such as angiogenesis, anti-apoptosis, 
cell migration and proliferation in a variety of cancer entities. 


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1.3.2. 
Erdafitinib 
 
Erdafitinib is a highly selective and potent oral pan-FGFR tyrosine kinase inhibitor with high 
affinity and low nanomolar inhibitory activity for all FGFR family members, FGFR 1, 2, 3 and 4. 
In FGFR pathway activated cancer cell lines, the concentration required for 50% inhibition 
(IC50) is in the low nanomolar range 0.1 to 129.2 nM. It has demonstrated activity in FGFR 
pathway-activated cancer cell lines including squamous non-small cell lung cancer (NSCLC), 
gastric, breast, hepatocellular cancer (HCC), endometrial, bladder, multiple myeloma, and acute 
myeloid leukemia. Non-FGFR driven cell lines require significantly higher drug concentration 
for inhibition of cell proliferation to be observed. Target inhibition and pathway modulation have 
been demonstrated in cellular models at active cellular concentrations. Brief exposure to 
erdafitinib has been demonstrated to result in long-term target inhibition. Erdafitinib has been 
shown to have in vivo antitumor activity in mouse xenograft models of FGFR-driven gastric, 
bladder, and squamous NSCLC tumor models, and in patient-derived xenografts from squamous 
NSCLC, gastric, breast, and hepatocellular tumors. 
 
In humans, absorption of erdafitinib was estimated to be near complete. Following single and 
multiple once-daily administration, erdafitinib exposure (Cmax and AUC) increased in a dose- 
proportional manner across the dose range of 0.5 to 12 mg. Multiple dose erdafitinib PK was time 
independent and steady state was achieved after 2 weeks of daily administration. With a once daily 
dose regimen, mean (coefficient of variation [CV%]) steady state accumulation ratio for AUC 
from time 0 to 24 hours after daily dosing (AUCτ) was 4.07 (32.0%), corresponding to a mean 
effective half-life (t1/2) of 58.9 hours. 
 
For the most comprehensive nonclinical and clinical information regarding erdafitinib, refer to the 
latest version of the Investigator's Brochure and Addenda for erdafitinib (Erdafitinib IB). 
 
1.3.2.1. 
Erdafitinib Efficacy 
 
Study BLC2001: 
 
This is an ongoing Phase 2, multicenter, open-label study to evaluate the efficacy and safety of 
single- agent erdafitinib in subjects with advanced ie, metastatic or surgically unresectable 
urothelial carcinoma and whose tumors had certain FGFR genetic alterations. 
 
Key efficacy results are based on response for the 87 chemo-relapsed/refractory subjects in the 8- 
mg daily regimen. Responses were assessed using Response Evaluation Criteria in Solid Tumors 
(RECIST), (version 1.1). Investigator assessed response indicated that the primary objective had 
been met (objective response rate [ORR] of 40% and the lower bound of the 95% CI exceeding 
25%). IRRC assessment of response for subjects treated in the 8-mg daily regimen was 
comparable to that reported by investigator. Responses were rapid and durable, with a median 
time to first response of 1.41 months and median duration of response (DOR) of 5.98 months. 
An estimated 30% of responders had response for more than 1 year. Median progression-free 
survival (PFS) was 5.52 months, with a median follow up of 11.2 months. Median overall 
survival (OS) was 13.8 months and the 12-month survival rate was 53%. 


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Study EDI1001: 
 
This was a Phase 1, first-in-human, open label, multicenter, 4-part, dose escalation study to 
explore the safety, PK, and pharmacodynamics (PD) of erdafitinib administered orally to adult 
subjects with advanced or refractory solid malignancies or lymphoma. 
 
Of the 187 subjects treated in this study, 30 subjects had urothelial carcinoma. The 10 subjects 
treated with erdafitinib 9 mg once daily who responded to treatment with erdafitinib all carried 
mutations or translocations in FGFR. The ORR for response-evaluable urothelial subjects with 
FGFR mutations or translocations was 70.0% which included 7 subjects with PR. 
 
All 9 subjects with cholangiocarcinoma carried mutations or translocations of FGFR. The ORR 
for response-evaluable subjects with cholangiocarcinoma was 27.3%; 3 subjects achieved PR. 
 
Study HCC1001: 
 
Study HCC1001 is an open-label, multicenter, 2-part, Phase 1/2a study to evaluate the safety, PK, 
PD, and clinical responses of erdafitinib administered orally to Asian subjects ≥18 years of age 
and with advanced HCC. 
 
Of the 53 subjects treated, 52 subjects with advanced HCC were evaluable for response. The best 
response to treatment was PR, for 2 subjects in the 10-mg intermittent group. The ORR was 3.8% 
for all response-evaluable subjects, and 4.8% for 42 response-evaluable subjects with FGF19 
amplification. This low response rate led to the discontinuation of recruitment to the study. 
 
Study LUC1001: 
 
Study LUC2001 is an open-label, multicenter, phase 2a clinical study to evaluate the clinical 
efficacy, safety, and PK of erdafitinib in Asian subjects with selected FGFR translocations or 
mutations, RET activating mutations or translocations, or other evidence of FGFR pathway 
activation. 
 
Of the 24 subjects treated, 23 subjects were evaluable for response. The ORR was 26.1%; 6 
subjects had a PR. For the 11 subjects with cholangiocarcinoma, all of whom were treated with 8- 
mg daily and who had an FGFR2 mutation of translocation, 5 subjects had a confirmed PR, for an 
ORR of 45.5% and 9 subjects had at least SD, for a disease control rate (DCR) of 81.8%. 
 
1.3.2.2. 
Erdafitinib Safety 
In pooled analyses for subjects who received erdafitinib doses of 8 or 9 mg once daily in Studies 
EDI1001, BLC2001, and GAC1001, all 164 subjects experienced at least 1 adverse event (AE). 
The most frequently reported adverse events were hyperphosphatemia (81.7%), stomatitis 
(56.1%), dry mouth (45.7%), diarrhea (41.5%), decreased appetite (37.8%), constipation (35.4%), 
dysgeusia (35.4%), and dry skin (31.7%). Grade 3 or higher treatment-emergent adverse events 
(TEAEs) were reported for 66.5% of subjects. The most frequently reported Grade 3 or worse AEs 
were stomatitis (10.4%), hyponatremia (9.8%), asthenia (6.1%), anemia (5.5%), fatigue (4.3%), 
and dyspnea (3.7%). Serious adverse events (SAE) were reported for 40.9% of subjects. Thirty 
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(6.7%) had AEs that were fatal and included general physical health deterioration (2.4%) and 
asthenia (1.2%) in the context of disease progression. None of the fatal AEs were considered drug- 
related. 
 
Central serous retinopathy (CSR; inclusive of chorioretinopathy, detachment of macular retinal 
pigment epithelium, detachment of retinal pigment epithelium, retinal detachment, retinal edema, 
retinopathy, and vitreous detachment) is an adverse event of special interest. Adverse events of 
clinical importance include other eye disorders (excluding CSR), skin and nail changes, 
hyperphosphatemia, and arrhythmias. Adverse drug reactions include hyperphosphatemia, nail 
disorders, skin disorders, palmar-plantar erythrodysesthesia syndrome (PPES), and central serous 
retinopathy. 
 
1.4. 
Enzalutamide 
Enzalutamide works through competitive AR inhibition and, unlike the older anti-androgens (e.g. 
bicalutamide, nilutamide), is a pure AR antagonist. It additionally has the ability to prevent AR 
nuclear translocation and DNA binding to nuclear response elements23. It was approved in 2012 
for men with mCRPC post-docetaxel16 It has also gained approval for men who are 
docetaxel-naïve given that a recently completed Phase III study showed OS improvements in a 
pre-chemotherapy population as well9 In that patient population enzalutamide was shown to 
result in a 37% reduced risk of death compared to placebo (HR 0.63, 95% CI, 0.53-0.75; 
P<0.001)9. 
 
Enzalutamide was initially tested in a Phase I/II dose escalation trial24. In that study 
enzalutamide was tested at doses ranging from 30 mg to 600 mg by mouth daily. It was found to 
exert an antitumor effect at all doses tested, with a PSA response rate (i.e. ≥50% PSA declines) 
in 78 out of 140 enrolled subjects (56%). Fatigue was the most common adverse event (AE) and 
generally occurred following 30-days of treatment. At doses ≥240 mg daily, an increasing 
proportion of patients required dose reductions secondary to fatigue. Overall grade 3-4 AEs 
included: fatigue (11%), anemia (3%), arthralgia (2%), asthenia (2%) and seizures (2%). Overall 
mild (i.e. grade 2) AEs included: fatigue (27.1%), nausea (8.6%), dyspnea (7.9%), anorexia 
(5.7%) and back pain (5.7%). Two witnessed seizures and one questionable seizure occurred in 
patients receiving doses of 600 mg, 360 mg and 480 mg, respectively. Only 1/87 patients treated 
at a daily dose of ≤240 mg discontinued treatment for an AE, compared to 7/53 at doses ≥360 
mg. While 240 mg daily was deemed the maximum tolerated dose, it was noted that extent and 
proportion of patients achieving PSA decreases plateaued somewhere between 150 mg and 240 
mg daily. As such, enzalutamide 160 mg by mouth daily was ultimately selected for further 
investigation. 
 
On the basis of the aforementioned Phase I/II results, the AFFIRM trial, a large randomized 
Phase III study powered to detect differences in survival, was launched16 This enrolled men with 
CRPC who had already progressed on docetaxel. Subjects were randomized 2:1 between 
enzalutamide 160 mg daily (N=800) and placebo (N=399). This study met its primary endpoint, 
demonstrating a median OS of 18.4 months with enzalutamide compared to 13.6 months with 
placebo (HR for death, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The rate of AEs between 
enzalutamide and placebo were similar. Enzalutamide had a lower rate of grade 3 or higher AEs 
compared to placebo (45.3% vs 53.1%, respectively). Rates of fatigue, diarrhea and hot flashes 


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were higher with enzalutamide (Table 1). There were notably 5 patients (0.6%) that experienced 
a seizure in the enzalutamide arm compared to zero in the placebo arm. One of these seizure 
required medical intervention, the others were self-limited. Predisposing factors were present in 
several patients, and included: two subjects with brain metastases, one subject inadvertently 
received IV lidocaine prior to the seizure and one subject had brain atrophy and a history of 
heavy alcohol use. The results from this study ultimately lead to the approval of enzalutamide in 
men with CRPC who had already received prior docetaxel. 
 
More recently, the results of another randomized Phase III study, the PREVAIL trial, were 
released9 This study randomized men with CRPC who were docetaxel naïve between 
enzalutamide 160 mg daily (N=871) and placebo (N=844). As was the case with AFFIRM, the 
PREVAIL trial demonstrated an OS advantage with enzalutamide. The median OS improved 
from 30.2 months to 32.4 months with enzalutamide treatment (HR for death, 0.706; 95% CI, 
0.60 to 0.84; P<0.0001). While improvement in survival is modest, it should be noted that those 
in the placebo group received other proven prostate cancer therapies at a higher rate than those 
on the enzalutamide arm (e.g. 32.8% vs 56.7% received docetaxel and 20.5% vs 45.6% received 
abiraterone acetate). AEs occurred at comparable rates between the enzalutamide and placebo 
arms. 
 
Refer to Enzalutamide’s FDA label for additional pharmacology and clinical data. 


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PREVAIL 
AFFIRM 
 
 
Adverse 
Event 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1: Adverse events associated with enzalutamide. Data from the AFFIRM and 
PREVAIL trials9,16 
 
1.5. 
Abiraterone Acetate 
Developed through rational design based on a parent pregnenolone structure, abiraterone 
acetate functions through inhibition of cytochrome P450-17 (CYP-17), a key family of 
enzymes involved in gonadal, adrenal and intratumoral androgen synthesis25-27 When given in 
conjunction with a GnRH analogue, it has the ability to rapidly drive castrate level 
testosterone (i.e. <20-50 ng/dL) to undetectable28,29 Unlike ketoconazole, another CYP-17 
inhibitor used in the CRPC setting, abiraterone acetate is highly specific for the CYP-17 
family of enzymes, making it generally better tolerated than ketoconazole27,29,30. It can lead to 
mineralocorticoid excess, however, through a compensatory elevation in adrenocorticotropic 
hormone (ACTH) that occurs in response to depressed cortisol levels. When prednisone is 
co-administered with abiraterone acetate, mineralocorticoid associated side effects (e.g. fluid 
retention, hypokalemia and hypertension) are mostly prevented, although these are observed 
more frequently in those receiving abiraterone acetate compared to placebo10,15,31 Abiraterone 
acetate is currently FDA approved for the treatment of CRPC in patients who are either pre- 
Enzalutamide 
(N=871) 
All 
Grade 
Grades 
 3-4 
(%) 
(%) 
Placebo 
(N=844) 
All 
Grad 
es 
Grade 
(%) 
3-4 (%) 
Enzalutamide 
(N=800) 
Placebo (N=399) 
All 
All 
Grad 
Grade 
 
Grad es 
3-4
 
 es 
Fatigue 
35.6 
1.8 
25.8 
1.9 
34 
6 
29 
7 
Back pain 
27 
2.5 
22.2 
3 
Constipation 
22.2 
0.5 
17.2 
0.4 
Diarrhea 
21 
1 
18 
0.3 
Hot flashes 
20 
0 
10 
0 
Arthralgias / 
musculoskel 
etal pain 
20.3 
1.4 
16 
1.1 
14 
1 
10 
0.3 
Headache 
12 
0.8 
6 
0 
Cardiac 
event/disord 
er 
10.1 
2.8 
7.8 
2.1 
6.3 
1.1 
8 
2.5 
Hypertensio 
n 
13.4 
6.8 
4.1 
2.3 
6.6 
3.3 
Abnormal 
liver 
function 
testing 
0.9 
0.2 
0.6 
0.1 
1 
0.4 
2 
0.8 
Seizure 
0 
0 
0.1 
0 
0.6 
0.6 
0 
0 


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or post-docetaxel. 
 
Two dose escalation Phase I studies were completed utilizing abiraterone acetate28,32. Neither 
study documented dose-limiting toxicities, however, side effects of note included: hypertension 
(12-29%), hypokalemia (24-48%) and peripheral edema (5-24%). This side effect profile was felt 
most likely to be a result of mineralocorticoid excess secondary to a compensatory elevation in 
ACTH occurring in the context of partially blocking adrenal steroid synthesis. These side effects 
were managed with eplerenone, beta-blockers, diuretics and/or corticosteroids. Furthermore, 
these studies provided preliminary evidence for abiraterone acetate’s efficacy in men with 
chemotherapy naïve CRPC. 
 
A subsequent Phase II study evaluated abiraterone acetate in men with CRPC post-docetaxel 
treatment33. This study incorporated prednisone 5 mg twice daily into the treatment regimen in 
an effort to mitigate the aforementioned mineralocorticoid associated side effects. At a dose of 
1000 mg daily, abiraterone acetate was found to produce PSA declines of at least 50% in 22/58 
(36%) men. Partial responses by Response Evaluation Criteria in Solid Tumors (RECIST) 
criteria were seen in 4/22 (18%) patients with evaluable tumors. Importantly, no significant 
hypertension or hypokalemia was noted – likely due to the co-administration of prednisone. 
 
Proof of principle that further androgen suppression is effective in controlling CRPC was 
provided for in the landmark Phase III COU-AA-301 trial. In that study it was demonstrated that 
abiraterone acetate, when given to men with CRPC previously treated with docetaxel, resulted in 
a significant reduction in the risk of death compared to placebo (HR 0.65, 95% CI, 0.54-0.77; 
P<0.001)10. Subsequently the COU-AA-302 trial demonstrated similar efficacy in men with 
CRPC pre-docetaxel (HR 0.79, 95% CI, 0.66-0.96; P < .0151)15. These two trials demonstrated a 
higher incidence of mineralocorticoid associated side effects in spite of the co-administration of 
prednisone. Hypokalemia, peripheral edema and hypertension occurred at approximate rates of 
17%, 28-31% and 10-22% in the abiraterone acetate cohorts respectively. Other adverse events 
observed were generally low grade. Of note there did appear to be higher rates of fatigue, 
arthralgias, aminotransferase abnormalities and non-fatal cardiac events with abiraterone acetate. 
Overall, abiraterone acetate was felt to be generally well tolerated, however. A summary of the 
adverse events observed in these two Phase III trials are listed in Table 1. Ultimately, on the 
basis of the COU-AA-301 and COU-AA-302 trials abiraterone acetate was approved in the post- 
and pre-docetaxel setting respectively. 


PI: Michael T. Schweizer 
Protocol Version: 6.0 
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COU-AA-301 
COU-AA-302 
Adverse Event 
Abiraterone acetate + 
Prednisone (n=791) 
Placebo + Prednisone 
(n=394) 
Abiraterone acetate + 
Prednisone (n=542) 
Placebo + Prednisone 
(n=540) 
  
All Grades (%) 
Grade 3-4 
(%) 
All Grades 
(%) 
Grade 3-4 
(%) 
All Grades 
(%) 
Grade 3-4 
(%) 
All Grades 
(%) 
Grade 3-4 
(%) 
Anemia 
23 
7.5 
26 
7.4 
- 
- 
- 
- 
Thrombocytopenia 
4 
1.4 
3 
0.5 
- 
- 
- 
- 
Neutropenia 
1 
0.1 
0.3 
0.3 
- 
- 
- 
- 
Febrile neutropenia 
0 
0 
0 
0 
- 
- 
- 
- 
Diarrhea 
18 
0.6 
53 
1.3 
22 
18 
  
Fatigue 
44 
8.3 
169 
9.9 
39 
34 
  
Asthenia 
13 
2.3 
52 
2 
- 
- 
- 
- 
Back pain 
30 
5.9 
129 
9.6 
32 
32 
  
Nausea 
30 
1.6 
124 
2.5 
- 
- 
- 
- 
Vomiting 
21 
1.8 
97 
2.8 
- 
- 
- 
- 
Hematuria 
8 
1.4 
31 
2.3 
- 
- 
- 
- 
Abdominal pain 
12 
2 
44 
1.5 
- 
- 
- 
- 
Pain in arm or leg 
17 
2.4 
79 
5 
17 
16 
  
Dyspnea 
13 
1.3 
46 
2.3 
- 
- 
- 
- 
Constipation 
26 
1 
120 
1 
23 
19 
  
Pyrexia 
9 
0.4 
35 
1.3 
- 
- 
- 
- 
Arthralgia 
27 
4.2 
89 
4.1 
28 
24 
  
Urinary tract infection 
12 
2.1 
28 
0.5 
- 
- 
- 
- 
Pain 
2 
0.6 
19 
1.8 
- 
- 
- 
- 
Bone pain 
25 
5.6 
110 
7.4 
20 
19 
  
Fluid retention or edema 
31 
2.3 
88 
1 
28 
0.7 
24 
2 
Hypokalemia 
17 
3.8 
33 
0.8 
17 
2 
13 
2 
Cardiac disorder* 
13 
4.1 
42 
2.3 
19 
6 
16 
3 
Liver-function test 
abnormalities or 
Hepatotoxicity 
10 
3.4 
32 
3 
4.2 
8 
9.8 
3 


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Hypertension 
10 
1.3 
31 
0.3 
- 
- 
- 
- 
Hot flush 
- 
- 
- 
- 
22 
18 
  
Muscle spasm 
- 
- 
- 
- 
14 
20 
  
Cough 
- 
- 
- 
- 
17 
  
14 
  
Table 2: Adverse events observed on the COU-AA-30110 and COU-AA-30234 trials. 
*Cardiac disorders included: ischemic heart disease, myocardial infarction, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, cardiac 
failure and possible arrhythmia-related tests, signs and symptoms 
 


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Abiraterone acetate plus the GnRH agonist leuprolide have also been tested in the neoadjuvant 
setting. Taplin and colleagues recently reported on the results of a randomized Phase II study35 
In that trial men were randomized between 24 weeks of neoadjuvant GnRH agonist plus 12 
weeks of abiraterone acetate (N=28) and 24 weeks of both neoadjuvant GnRH plue abiraterone 
acetate (N=30). That trial demonstrated a negative margin rate of 90% and pCR rate of 10% in 
the cohort receiving 24 weeks of both leuprolide and abiraterone acetate, with an additional 14% 
of patients achieving a near pCR (defined as ≤5 mm residual tumor). The cohort receiving 24 
weeks of GnRH agonist and 12 weeks of abiraterone acetate achieved a negative margin rate of 
81%, a pCR rate of 4% and a near pCR rate of 0%. Differences in pathologic outcomes between 
cohorts were not statistically significant; although, the trial was not powered to detect these 
differences. 
 
 
1.6. 
Overall Rationale for the Study 
Many of the treatments for mCRPC are directed at suppressing the AR-signaling axis. While 
AR-directed therapies are initially effective, resistance inevitability occurs. The continued 
lethality of this disease underscores the importance of testing therapeutics aimed at alternate 
pathways. As outlined above, mechanistic studies have revealed that MAPK-signaling, which is 
activated by FGF/FGFR signaling, is an important AR bypass mechanism in men with late stage, 
DNPC. Importantly, targeting FGF/FGFR-signaling with pan-FGFR inhibitors results in 
significant tumor growth inhibition in both engineered LNCaPAPIPC cells and DNPC LuCaP 
173.2 PDX models1. It is important to note that unlike other malignancies (e.g. bladder and lung 
cancer), patients with a DNPC phenotype usually do not harbor genomic alterations in FGFR, 
and over-activation of FGF/FGFR-signaling is primarily driven by autocrine/paracrine activation 
of this pathway. In total, this data demonstrates that FGF/FGFR-signaling is a critical driver of 
late stage CRPC, and supports testing FGFR inhibitors in DNPC patients. 
 
On this basis, we are launching a phase II trial testing the pan-FGFR inhibitor erdafitinib in men 
with metastatic CRPC who have previously progressed on abiraterone acetate and/or 
enzalutamide and exhibit a DNPC phenotype on biopsy. Patients will continue on the most 
recent next-generation AR-directed therapy they progressed on (i.e. either abiraterone acetate or 
enzalutamide) in order to maintain suppression of AR-signaling, and erdafitinib will be added to 
their regimen. Erdafitinib will be dosed at the recommended Phase II dose, and abiraterone 
acetate or enzalutamide will be administered at their respective FDA approved dose. Study 
subjects will continue on erdafitinib plus either abiraterone acetate or enzalutamide until 
radiographic progression or intolerable toxicity. We hypothesize that erdafitinib in combination 
with a next-generation AR-directed therapy will show clinical efficacy in men with mCRPC with 
a DNPC phenotype who have progressed on abiraterone acetate or enzalutamide 
 
2. 
OBJECTIVE AND ENDPOINTS 
 
2.1. 
Primary Objective 
 
To determine the objective tumor response rate in subjects with measurable lesions as defined by 
RECIST v1.1 criteria in mCRPC patients with a DNPC molecular phenotype receiving either 
enzalutamide or abiraterone acetate in combination with erdafitinib. 


29 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
 
 
2.2. 
Secondary Objectives 
 
1. Determine the radiographic PFS in patients using RECIST 1.1 criteria for soft tissue 
metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for bone 
metastases2,3 
2. Determine the time to response using RECIST 1.1 criteria2 
3. Determine the overall survival defined as the time interval from C1D1 to the date of 
death 
4. PSA response, defined as >50% reduction in PSA compared with baseline at any point 
during treatment 
5. Assess the incidence and severity of adverse events according to National Cancer 
Institute- Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 
 
2.3. 
Planned Exploratory Objectives 
 
Correlative work will be performed in order to determine biomarkers predictive of response to 
combination therapy. Examples of correlative work may include, but will not be limited to: 
 
1. Immunohistochemistry (IHC) for phosphorylated FGFR and FGFR substrate 2 (FRS2) in 
tumor tissue 
2. IHC for PSA and AR expression in tumor tissue 
3. Tumor tissue transcript profiling studies to assess candidate biomarkers for 
response/resistance to FGFR inhibitor therapy and to evaluate core signaling program for 
FGF/FGFR, MAPK, and AR. 
4. Next-generation sequencing of pre-treatment tumor biopsies and cell-free circulating 
tumor DNA (ctDNA) to identify genomic alterations correlating with response or 
resistance to treatment, and confirm FGFR alteration status 
5. Serial blood (baseline, 12-weeks, progression) will be obtained in order to develop a 
blood-based gene expression response signature 
6. Serum FGF ligand levels (FGF8, FGF9, FGF19) will be drawn at baseline,12-weeks and 
at progression 
 
 
3. 
STUDY DESIGN AND RATIONALE 
This will be a phase II trial testing the pan-FGFR inhibitor, erdafitinib, in men with metastatic 
CRPC who have previously progressed on abiraterone acetate and/or enzalutamide (Fig 7). Eligible 
patients must have CRPC (defined as disease progression in spite of a castrate serum testosterone 
[≤50 ng/dl]), and evidence of RECIST evaluable disease to enroll2. Given that the patient 
population of interest will be heavily pre-treated, and likely enriched for both small cell/NE and 
double negative prostate cancer, it is recommended that patients undergo a baseline  biopsy prior to 
enrollment to rule out predominate NE/small cell variant prostate cancer. Patients with DNPC as 
defined by IHC criteria will be eligible to enroll (see Section 9.2.1.1). Transcript profiling methods 
for identifying DNPC may also be accepted for determining trial eligibility at the PI’s discretion. 
This is based on data showing that transcriptional signatures can accurately define the various 
prostate cancer subtypes, including DNPC4,5. Eligible patients must have demonstrated evidence of 
progression per Prostate Cancer Working Group 3 (PCWG3) criteria while on enzalutamide or 


30 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
abiraterone acetate at any time prior to enrollment3. If not surgically castrated, participants must be 
maintained on an LHRH analogue (e.g. leuprolide, goserelin).  
 
Eligible patients will continue on the most recent next-generation AR-directed therapy they 
progressed on (i.e. either abiraterone acetate or enzalutamide) in order to maintain suppression of 
AR-signaling and erdafitinib will be added to their regimen. If a trial subject is not currently on 
abiraterone or enzalutamide at the time of screening, they must restart the AR-directed therapy 
most recently received and demonstrate two successive PSA rises or other evidence of 
progression prior to starting treatment per protocol. Erdafitinib will be administered at 8 mg once 
daily orally, with pharmacodynamic uptitration to 9 mg if serum phosphate was below 5.5mg/dL in 
absence of significant toxicity on cycle 1 day 14 (see Section 6.1). 
 
Abiraterone acetate or enzalutamide will be administered at their respective FDA approved dose 
(i.e. abiraterone acetate 1000 mg PO daily; enzalutamide 160 mg PO daily). Subjects continuing 
on abiraterone acetate will also be required to receive prednisone 5 mg PO twice daily in order to 
blunt mineralocorticoid symptoms associated with abiraterone acetate. Study subjects will 
continue on erdafitinib plus either abiraterone acetate or enzalutamide until radiographic 
progression, intolerable toxicity or two-years of treatment, whichever comes first. 
 
The primary objective will be to determine the objective tumor response rate in measurable 
lesions as defined by RECIST v1.1 criteria.  For the purpose of defining objective response rate, 
confirmation of response will not be required. If a patient drops out of the study prior to first on- 
study radiographic assessment, they will be considered a non-responder for the purpose of the 
primary analysis; however, an additional subject will be accrued to account for early dropouts. 
Key secondary objectives will include determining: radiographic progression free survival (PFS) 
in patients using RECIST 1.1 criteria for soft tissue metastases and Prostate Cancer Working 
Group 3 (PCWG3) criteria for bone metastases; time to response using RECIST 1.1 criteria; 
overall survival (OS) defined as the time interval from C1D1 to the date of death; PSA response, 
defined as >50% reduction in PSA compared with baseline at any point during treatment; and the 
incidence and severity of adverse events according to National Cancer Institute-Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.02,3. 
 
This study will also include a number of correlative studies aimed at identifying candidate 
biomarkers for response/resistance to FGFR inhibitor therapy. We will plan to obtain pre- and 
post-treatment biopsies as well as serial blood samples in order to develop blood-based 
biomarkers for response/resistance to erdafitinib. Given our rapidly evolving understanding of 
prostate cancer biology, it is impossible to prospectively define all the relevant biomarkers for 
the patient population enrolled on this study. Examples of the studies to be conducted may 
include, but will not be limited to the following. Protein expression studies at baseline and at the 
time of progression, including IHC for AR, PSA, phospho-FRS2 and phosphor-FGFR. 
Transcript profiling studies (RNA-seq) on metastatic biopsies to assess activation of the core 
AR-, MAPK- and FGF/FGFR-signaling programs, and to identify unknown pathways involved 
in mediating response/resistance to treatment. Next-generation sequencing to assess for FGFR 
mutations. Baseline protein and transcript expression, as well as changes in these parameters 
with treatment will be correlated with clinical outcomes. This information will be used to 
develop a gene expression response-signature, which we will be assessed in blood samples. 


31 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
 
 
Fig 7. Study schema. 
 
4. Subject Population 
 
 
Full study screening for eligible subjects will be performed within 30 days before administration of the study 
drug. 
 
The inclusion and exclusion criteria for enrolling subjects in this study are described in the following 2 
subsections. 
 
4.1 Inclusion Criteria 
Each potential subject must satisfy all of the following criteria to be enrolled in the study: 
 
 
1. Patients must be > 18 years of age prior to signing informed consent 
 
2. History of histologically diagnosed prostatic adenocarcinoma 
 
3. Participants must have evidence of castration resistant prostate cancer as evidenced by a confirmed 
rising PSA or radiographic progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) 
and a castrate serum testosterone level (i.e. < 50 ng/dL) 
 
4. Participants must have previously progressed on abiraterone acetate and/or enzalutamide, with PSA 
or radiographic progression on the most recent agent per PCWG3 criteria. If the most recent agent 
received was abiraterone or enzalutamide there should be no washout prior to initiating erdafitinib 
per protocol 
 
5. Measurable disease as defined per RECIST v1.1 criteria 
 
6. Subjects who have progressed on only one next-generation AR-directed therapy (e.g. abiraterone, 
enzalutamide) and who have not received taxane chemotherapy will be required to have evidence of 
double-negative prostate cancer as defined by immunohistochemistry (see Section 9.2.1.1) on 
biopsy. A fresh metastatic biopsy within 8 weeks is preferred; however, any archival tissue showing 
a DNPC phenotype will be acceptable for determining eligibility. Patients who have received two 


32 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
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Version Date: 17 September 2020 
 
 
prior lines of AR-directed therapy and at least one prior taxane do not require histologic 
confirmation of DNPC.  
Note: transcript profiling methods for defining DNPC may be accepted per the PI’s discretion 
 
7. ECOG performance status score <2 
 
8. Clinical and laboratory values and cardiovascular measurements at screening: 
 
Hematology 
Hemoglobin 
> 8  g/dL (>5 mmol/L) (must be without 
red blood cell [RBC] transfusion within 7 
days prior to the laboratory test) 
Platelets 
> 75 x 109/L 
Absolute Neutrophil Count (ANC) 
> 1.5 x 109/L (prior growth factor support 
is permitted but must be without support in 
the 7 days prior to the laboratory test) 
Chemistry 
AST and ALT 
< 2.5 x upper limit of normal (ULN) or < 5 
x ULN for subjects with liver metastases 
Creatinine clearance 
>40 mL/min/1.73 m2 based upon Modified 
Diet in Renal Disease formula calculation 
Total bilirubin 
< 1.5 x ULN; except in subjects with 
congenital bilirubinemia, such as Gilbert’s 
syndrome 
Cardiovascular 
Corrected QT interal (QTcF or QTcB) 
<480 msec based on the average of 
triplicate assessments performed 
approximately 5 minutes apart 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; GFR = glomerular filtration rate; QTcB = QT corrected interval by the 
Bazett’s formula; QTcF = QT corrected interval by the Fridericia’s formula; ULN = 
upper limit of normal 
IF Glibert’s disease is present, direct bilirubin can be measured 
 
9. Subjects must agree to use acceptable contraception (see Section 11.3 for requirements) 
 
10. Must sign an informed consent form (ICF) indicated that he or she understands the purpose of, and 
procedures required for, the study and is willing to participate in the study 
 
Exclusion Criteria 
 
1. Treatment with any other investigational agent or participation in another clinical trial with 
therapeutic intent within 14 days prior to enrollment 
 
2. Active malignancies (i.e. requiring treatment change in the last 24 months) other than malignancy 
under study (except skin cancers within the last 24 months that are considered completely cured) 
 


33 
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3. Evidence of predominant small cell or neuroendocrine variant prostate cancer (see section 9.2.1.1) 
on most recent standard of care metastatic biopsy 
 
4. Symptomatic central nervous system (CNS) metastases. Treated CNS metastases will be allowed if 
these are stable for at least 8 weeks prior to enrollment 
 
5. Received prior FGFR inhibitor treatment or if the subject as known allergies, hypersensitivity, or 
intolerance to erdafitinib or its excipients 
 
6. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade  
 
7. Has persistent phosphate level >ULN during screening (on 2 consecutive assessments at least 1 week 
apart, within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management 
 
8. Has a history of current uncontrolled cardiovascular disease including: 
 
a. Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac 
arrest, or known congestive heart failure Class III-V within the preceding 3 months; 
cerebrovascular accident or transient ischemic attack within the preceding 3 months 
 
b. Pulmonary embolism or other VTE (venous thromboembolism) within the preceding 2 
months 
 
9. Has known active AIDS (human immunodeficiency virus (HIV) infection) 
 
10. Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. 
In the event the infection status is unclear, quantitative levels are necessary to determine the 
infection status. Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA 
quantitation positive) or known to have a history of hepatitis C. If positive, further testing of 
quantitative levels to rule out positivity is required 
 
11. Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are 
not clinically significant such as alopecia, skin discoloration, hot flashes, Grade 1 neuropathy, Grade 
1-2 hearing loss) 
 
12. Has impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known 
gastric ulcers, or unhealed incisions 
 
13. Major surgery within 2 weeks of the first dose, or will not have fully recovered from surgery, 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) 
 
14. Any serious underlying medical conditions, such as: 
a. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection 
 
b. Active autoimmune or a documented history of autoimmune disease 
 


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c. Psychiatric conditions (e.g., alcohol or drug abuse), dementia, or altered mental status 
 
15. 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 (e.g., 
compromise the well-being) or that could prevent, limit, or confound the protocol-specified 
assessments 
 
16. Patient, who, in the opinion of their treating physician, requires immediate treatment (e.g. those with 
extensive liver metastases)  
 
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, Screening Phase, describes options for retesting. Section 17.4, Source Documentation, 
describes the required documentation to support meeting the enrollment criteria. 
 
 
 
5 TREATMENT ALLOCATION AND BLINDING 
 
6 DOSAGE AND ADMINISTRATION
6.1 Erdafitinib 
Erdafitinib will be provided as a tablet for oral administration. Subjects will be instructed to take 
erdafitinib orally once daily for 21 days on a 21-day cycle. Treatment will be up-titrated to 9 mg, 
maintained at 8 mg, or withheld, based on phosphate level measured on Cycle 1 Day 14, and taking 
into account observed toxicity to that day. Erdafitinib is to be taken with approximately 240 mL 
(8 ounces) of water. The tablets should be swallowed intact and subjects should not attempt to 


35 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
dissolve them in water. Each dose should be taken at approximately the same time each day. 
Subjects should avoid consuming grapefruit or Seville orange, due to CYP450 3A4/5 inhibition 
by such fruits. 
 
Up-titration Guidelines 
All subjects will start erdafitinib 8 mg once daily from Day 1 to Day 14. On Day 14, a blood 
sample will be drawn to determine serum phosphate concentration. 
 
• 
Subjects with serum phosphate levels higher than 9 mg/dL will withhold erdafitinib treatment, 
with at least weekly assessment of serum phosphate until it returns to less than 7.0 mg/dL (see 
Table 4 for detailed guidelines regarding further treatment). 
• 
Subjects with serum phosphate levels between 7.0 to 9.0 mg/dL should increase the erdafitinib 
dose to 9 mg once daily, while concurrently initiating treatment with a phosphate binder such 
as sevelamer (see Table 4 for details). 
• 
Subjects with serum phosphate level less than 7.0 mg/dL will increase the erdafitinib dose to 
9 mg once daily without concomitant phosphate binder such as sevelamer. 
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 per institutional guidelines). 
 
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. 
 
6.1.1 Dose Modifications and Dose Delays for Erdafitinib 
Treatment with erdafitinib should be discontinued or modified based on toxicity as described in 
Table 1. For eye, skin/nail, dry mouth/mucositis, liver, and phosphate toxicity, specific 
recommendations in the management guidelines are provided in Sections 6.1.2.2 through 6.1.2.7. 
 
Table 1.        Erdafitinib Dose Modification Rules Based on Toxicity 
 
Toxicity 
Grade 
Action 
Dose modification after resolution of AE 
1 
None 
Continue same dose 
2 
None or consider interruption 
If interrupted, restart at same dose or 1 dose lower, if necessary. 
3 
Interrupt drug 
Restart at 1 or 2 doses lower if recovery (to ≤Grade 1 or back to 
baseline for non-hematologic toxicity) is within 28 days. 
Discontinue drug if unresolved for >28 days. 
4 
Interrupt drug 
Discontinue* 
a For eye, skin/nail, dry mouth/mucositis, liver, and phosphate toxicity please follow specific recommendations in the 
management guidelines. 


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PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
• 
Subjects with any grade of toxicity (Grade 1 to 4) should be provided symptomatic treatment 
where applicable. 
• 
If erdafitinib is interrupted consecutively for 1 week or longer due to drug-related toxicity, 
erdafitinib may be reintroduced at either the same dose level or the first reduced dose level 
following recovery from the toxicity (see dose reduction levels in Table 2). A second dose 
reduction may be implemented following a second occurrence of drug-related toxicity. 
• 
If erdafitinib must be withheld for more than 28 days for a drug-related adverse event that 
fails to resolve to acceptable level (e.g., ≤Grade 1 non-hematologic toxicity or back to 
baseline), treatment with erdafitinib should be discontinued except when the subject has been 
deriving benefit from treatment, and the investigator can demonstrate that continued treatment 
with erdafitinib is in the best interest of the subject. Erdafitinib may be re-started at the same 
or a lower dose (Table 2) if the Sponsor-Investigator (Dr. Schweizer) concurs with the 
assessment. 
• 
If erdafitinib was dose-reduced and the adverse event that was the reason for this dose- 
reduction has completely resolved, the dose may be re-escalated to the next higher dose if the 
subject was deriving benefit from treatment, and the investigator can demonstrate that dose 
re-escalation of erdafitinib is in the best interest of the subject and the Sponsor-Investigator 
concurs with the assessment. 
• 
In all cases of clinically significant impaired wound healing or imminent surgery or potential 
bleeding complications, it is recommended that dose administration be interrupted, 
appropriate clinical laboratory data (e.g., coagulation) be carefully monitored, and supportive 
therapy administered, where applicable. Dose administration may be restarted when it is 
considered safe and at an appropriate dose, according to the investigator’s assessment. 
 
 
Dose modification rules are provided in Table 2. 
Table 2. 
Erdafitinib Dose Reduction Levels 
 
Category 
No up-titration 
With up-titration 
Dose 
Dose 
Starting dose 
6 mg 
8 mg 
8 mg 
Up-titration 
None 
None 
9 mg 
1st dose reduction 
5mg 
6 mg 
8 mg 
2nd dose reduction 
4mg 
5 mg 
6 mg 
3rd dose reduction 
stop 
4 mg 
5 mg 
4th dose reduction 
stop 
4 mg 
5th dose reduction 
stop 


37 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
6.1.2 Guidance for Specific Erdafitinib Toxicities 
 
6.1.2.1 Grading of Hyperphosphatemia and Nail Disorders 
Hyperphosphatemia and adverse events related to nails will be graded as outlined in Table 3. 
 
Table 3: 
Grading of Hyperphosphatemia and Nails Adverse Events 
Adverse Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nail Changes 
(onychodystrophy) 
Nail discoloration, 
asymptomatic 
separation of the 
nail bed from the 
nail plate or nail 
loss 
Nail/finger tips 
pain, symptomatic 
separation of the 
nail bed from the 
nail plate or nail 
loss; limiting 
instrumental ADL 
Severe nail finger 
tips pain, 
symptomatic 
separation of the 
nail bed from the 
nail plate or nail 
loss; significantly 
limiting 
instrumental ADL 
Life-threatening 
consequences, 
urgent   intervention 
indicated 
Hyperphosphatemia 
5.5-6.9 mg/dl 
1.8-2.2 mmol/L 
7.0-8.9 mg/dl 
2.3-2.9 mmol/L 
9.0-10.0 mg/dl (2.9- 
3.2 mmol/L), or 
asymptomatic soft 
tissue calcification 
with any phosphate 
level 
>10 mg/dl (>3.2 
mmol/L), or 
symptomatic soft 
tissue calcification 
with any phosphate 
level 
 
 
6.1.2.2 Guidelines for the Management of Elevated Phosphate Levels 
Guidelines for the clinical management of elevated serum phosphate levels are presented in 
Table 4. Hyperphosphatemia should be graded according to Table 3. 
 
Table 4: 
Guidelines for Management of Serum Phosphate Elevation 
Serum Phosphate 
Level 
Study Drug Management 
Symptom Management 
<5.5 mg/dL 
(<1.8 mmol/L) 
Continue erdafitinib treatment. 
None. 
5.5-6.9 mg/dL 
(1.8-2.2 mmol/L) 
Continue erdafitinib treatment. 
Restriction of phosphate intake to 
600 – 800 mg/day. 
7.0-9.0 mg/dL 
(2.3-2.9 mmol/L) 
Continue erdafitinib treatment. 
A dose reduction will be implemented for persistenta 
hyperphosphatemia defined as serum phosphate 
≥7 mg/dL for a period of 2 months) or if clinically 
necessary (e.g., in the presence of additional adverse 
events linked to hyperphosphatemia or electrolyte 
disturbances) 
Restriction of phosphate intake to 
600 – 800 mg/day. 
Start sevelamer 800 to 1,600 mg 
TID with food until phosphate 
level is <7.0 mg/dL. 
>9.0-10 mg/dL 
(>2.9-3.2 mmol/L) 
Withholdb erdafitinib treatment until serum phosphate 
level returns to <7.0 mg/dL (weekly testing 
recommended). 
Re-start treatment at the same dose level. 
A dose reduction will be implemented for persistenta 
hyperphosphatemia (defined as serum phosphate 
Restriction of phosphate intake to 
600 – 800 mg/day. 
Sevelamer up to 1,600 mg TID 
with food until serum phosphate 
level returns to <7.0 mg/dL. 


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PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
 
Table 4: 
Guidelines for Management of Serum Phosphate Elevation 
Serum Phosphate 
Level 
Study Drug Management 
Symptom Management 
≥9 mg/dL for a period of 1 month) or if clinically 
necessary (e.g., in the presence of additional adverse 
events linked to hyperphosphatemia or electrolyte 
disturbances) 
>10.0 mg/dL 
(>3.2 mmol/L) 
Withholdb erdafitinib treatment until serum phosphate 
level returns to <7.0 mg/dL (weekly testing 
recommended). 
Re-start treatment at the first reduced dose level. 
If persistenta hyperphosphatemia (≥10 mg/dL) for >2 
weeks, erdafitinib should be discontinued 
permanently. 
Medical management as clinically 
appropriate. 
Significant 
alteration in 
baseline renal 
function or Grade 3 
hypocalcemia 
Erdafitinib should be discontinued permanently. (In 
situations where the subject is having clinical benefit 
and the investigator and the Sponsor-Investigator 
agree that continuation of treatment is in the best 
interest of the subject, the drug may be re-started at 2 
dose levels lower if appropriate. Follow other 
recommendations described above.) 
Medical management as clinically 
appropriate. 
Note: These are general guidelines that are based on emerging data and consensus experience of participating investigators or 
the experts in the field. The treating physicians must use clinical judgment and local standard of care to decide the best way to 
manage phosphate elevation. If sevelamer hydrochloride (Renagel®) is not available, use of other phosphate binders (non- 
calcium containing) based on the local standard is recommended, including sevelamer carbonate (Renvela) or lanthanum 
carbonate (Fosrenol®). These guidelines will be updated based on emerging data. Additional information on phosphorous in 
foods by class of food can also be found at www.permanente.net/homepage/kaiser/pdf/42025.pdf. Additional information for 
phosphate management and diet can be found at the National Kidney Foundation website 
(http://www.kidney.org/atoz/content/phosphorus.cfm) 
a. Persistent hyperphosphatemia is considered to be more than 1 sequential phosphate value above the cut-off. 
b. Study drug interruptions for hyperphosphatemia suggested to be 7 days duration. 
 
 
6.1.2.3 Guidelines for the Management of Dry Mouth and Stomatitis 
Guidelines for the clinical management of dry mouth (xerostomia) and stomatitis are provided in 
Table 5 and Table 6, respectively. 
 
• 
General Prophylaxis: 
− 
Good oral hygiene 
− 
Use a soft toothbrush 
− 
Avoidance of spicy, acidic, hard, and hot food and beverages 
− 
Use of mild-flavored toothpastes 
− 
Use of saline-peroxide or salt and baking soda mouthwashes 3 or 4 times per day 
− 
Water soluble lubrication agents like artificial saliva (for xerostomia or dry mouth) 


39 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
 
Table 5: 
Guidelines for the Management of Dry Mouth (Xerostomia) 
Grade and Definition 
Study Drug Management 
Symptom Management 
Grade 1: symptomatic (e.g., dry or thick saliva) 
without significant dietary alteration; 
unstimulated saliva flow >0.2 mL/min 
Continue erdafitinib at 
current dose. 
Sorbitol lozenges PRN 
Grade 2: moderate symptoms; oral intake 
alterations (e.g., copious water, other 
lubricants, diet limited to purees and/or soft, 
moist foods); unstimulated saliva 0.1 to 0.2 
mL/min 
Continue erdafitinib at 
current dose. 
Sorbitol lozenges PRN and 
Cevimiline 30 mg TID or 
Pilocarpine 5 mg TID 
Grade 3: inability to adequately aliment orally; 
tube feeding or TPN indicated; unstimulated 
saliva less than 0.1 ml/min 
Hold erdafitinib (for up to 
28 days), with weekly 
reassessments of clinical 
condition. 
When resolved to ≤Grade 
1 or baseline, restart at 1 
dose level below in 
consultation with the 
Sponsor-Investigator. 
Sorbitol lozenges PRN and 
Cevimiline 30 mg TID or 
Pilocarpine 5 mg TID 
Grade 4: life-threatening consequences, 
urgent intervention indicated 
Discontinue erdafitinib. 
Evaluation and therapy as 
clinically indicated 
 
 
 


40 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
Table 6: 
Guidelines for the Management of Oral Mucositis 
Grade 
Study Drug Management 
Symptom Management 
Grade 
1 
Continue study drug at current dose. 
• Continue general prophylaxis 
recommendations. 
• Dexamethasone solution (0.5 mg/5mL 
solution) swish and spit QID 
or similar solution that is available in your 
country 
and lidocaine 2-5% jelly or solution. 
• Consider clotrimazole/nystatin if subjects are 
at risk of developing oral candidiasis. 
Grade 
2 
• Consider holding study drug if the 
subject has other study-drug related 
concomitant Grade 2 AEs. 
• Hold study drug if the subject was 
already on symptom management 
(dexamethasone solution swish and 
spit and lidocaine 2-5% jelly or 
solution) for more than a week. 
• If the study drug is withheld, reassess 
in 1-2 weeks. 
• If this is the first occurrence of 
toxicity and resolves to ≤Grade 1 or 
baseline within 2 weeks, restart at 
same dose. 
• If  recurrent event or takes >2 weeks 
to resolve to ≤Grade 1 or baseline, 
then restart at 1 dose level below. 
• Dexamethasone solution (0.5 mg/5mL 
solution) swish and spit QID 
or similar solution that is available in your 
country and lidocaine 2-5% jelly or solution. 
• Consider concomitant etiologies such as oral 
candidiasis, oral herpes and recommend 
appropriate anti-fungal or anti-viral agents. 
Grade 
3 
• Hold study drug, with reassessments 
of clinical condition in 1-2 weeks. 
• When resolves to ≤Grade 1 or 
baseline, restart at 1 dose level below 
in consultation with the medical 
monitor. 
• Dexamethasone solution (0.5 mg/5mL 
solution) swish and spit QID 
or similar solution that is available in your 
country  
and lidocaine 2-5% jelly or solution. 
• Consider pain management strategies. 
• Consider IV hydration. 
Grade 
4 
Discontinue study drug. 
Evaluation and therapy as clinically indicated. 
AE=adverse event; QID=quater in die (four times each day). 
 
 
6.1.2.4 Guidelines for the Management of Dry Skin and Skin Toxicity 
Guidelines for the management of dry skin are provided in Table 7. 


41 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Protocol Number: CC10288 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
Version Date: 17 September 2020 
 
 
• 
General prophylaxis: 
− 
Avoid unnecessary exposure to sunlight and excessive use of soap. 
− 
Avoid bathing in excess; use tepid rather than hot water. 
− 
Use moisturizers regularly; apply thick, alcohol-free and oil-in-water based emollient 
cream on exposed and dry areas of the body. 
− 
Avoid perfumed products, bubble bath, perfumed soaps, and take breaks from shaving. 
− 
Use broad spectrum sunscreen with a skin protection factor (SPF) ≥15. 
− 
Wear cotton clothes next to skin rather than wool, synthetic fibers, or rough clothing. 
− 
Use occlusive alcohol-free emollient creams (jar or tub) for treatment of mild/moderate 
xerosis. 
− 
For scaly areas, use exfoliants (ammonium lactate 12% or lactic acid cream 12%). 
 
 
Table 7: 
Guidelines for Management of Dry Skin 
Grade and Definition 
Study Drug Management 
Symptom Management 
Grade 1: Dry skin covering less 
than 10% body surface area (BSA) 
and no associated erythema or 
pruritus 
Continue erdafitinib at current dose. 
Use fragrance free moisturizing 
cream or ointment BID over entire 
body. 
Use ammonium lactate 12% cream 
or salicylic acid 6% cream BID 
over dry/scaly/hyperkeratotic areas 
such as palms and soles. 
Grade 2: Dry skin covering 10 to 
30% BSA and associated with 
erythema or pruritis with limited 
instrumental activities of daily 
living (IADL) 
Continue erdafitinib at current dose. 
Use fragrance free moisturizing 
cream or ointment BID over entire 
body. 
Use ammonium lactate 12% cream 
or salicylic acid 6% cream BID 
over dry/scaly/hyperkeratotic areas 
such as palms and soles. 
Use zinc oxide 13-40% at night for 
areas with fissures. 
Grade 3: Dry skin covering >30% 
BSA and associated with pruritis; 
limiting self-care activities of daily 
living (ADL) 
Hold erdafitinib (for up to 28 days), 
with weekly reassessments of 
clinical condition. 
When resolves to ≤Grade 1 or 
baseline, restart at 1 dose level 
below in consultation with the 
Sponsor-Investigator. 
Use topical steroid ointment or 
cream* BID and zinc oxide 13-40% 
at night for areas with fissures. 
Grade 4: Dry skin with life- 
threatening consequences, urgent 
intervention indicated 
Discontinue erdafitinib. 
Evaluation and therapy as clinically 
indicated 
*Topical Steroid Ointments: Clobetasol 0.05%, Betamethasone 0.05%, Fluocinonide 0.05% 
 
 
6.1.2.5 Guidelines for Management of Nail Toxicity (Onycholysis, 
Onychodystrophy, and Paronychia) 
Guidelines for management of nail discoloration/loss/ridging (onycholysis/onychodystrophy) are 
provided in Table 8. Guidelines for the management of paronychia are provided in Table 9. 


42 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
• 
General Prophylaxis: 
− 
Good hygienic practices, keep fingers and toes clean. 
− 
Keep nails trimmed 
− 
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) 
− 
Trimming nails but avoiding aggressive manicuring 
 
 


43 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
Table 8: 
Guidelines for Management of Nail Discoloration/Loss/Ridging (Onycholysis/ 
Onychodystrophy) 
Grade  
Study Drug Management 
Symptom Management 
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 (periungal 
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 (periungal 
edema/erythema/ tenderness or discharge), 
obtain bacterial cultures, and then start the 
following: treatment with oral antibiotic for 
2 weeks (cefadroxil 500 mg BID, 
ciprofloxacin 500 mg BID, or 
sulfamethoxazole/trimethoprim BID). 
For cases 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. 
BID=bis in die (two times each day). 


44 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
 
Table 9: 
Guidelines for Management of Paronychia 
Grade and Definition 
Study Drug Management 
Symptom Management 
Grade 1: Nail fold edema or 
erythema; disruption of the cuticle 
Continue erdafitinib at current 
dose. 
Topical antibiotics AND vinegar 
soaksa 
Grade 2: Nail fold edema or 
erythema with pain; associated 
with discharge or nail plate 
separation; limiting instrumental 
ADL 
Continue erdafitinib at current 
dose. 
Consider erdafitinib holding if no 
improvement in 1 to 2 weeks. 
When resolves to ≤Grade 1 or 
baseline, restart at same or 1 dose 
level below in consultation with 
the Sponsor-Investigator. 
Topical antibiotics AND vinegar 
soaksa AND topical antifungal lacquer 
daily for 6+ weeks (ciclopirox olamine 
8% OR efinaconazole 10% OR 
amorolfine 5% weekly OR 
bifonazole/urea ointment daily) 
For signs of infection (periungal 
edema/erythema/tenderness and/or 
discharge), obtain bacterial cultures, 
and then start the following: treatment 
with oral antibiotic for 2 weeks 
(cefadroxil 500 mg BID, ciprofloxacin 
500 mg BID, or sulfamethoxazole/ 
trimethoprim (Bactrim) DS BID). 
Grade 3: Limiting self-care ADLs, 
surgical intervention, or 
intravenous antibiotics indicated 
Hold erdafitinib (for up to 28 
days), with weekly reassessments 
of clinical condition. 
When resolves to ≤ grade 1 or 
base line, restart at one dose level 
below in consultation with the 
Sponsor-Investigator. 
Vinegar soaksa AND consider nail 
avulsion 
For signs of infection (periungal 
edema/erythema/tenderness and/or 
discharge), obtain bacterial cultures, 
and then start the following: treatment 
with oral antibiotic for 2 weeks 
(cefadroxil 500 mg BID, ciprofloxacin 
500 mg BID, or sulfamethoxazole/ 
trimethoprim (Bactrim) DS BID). 
For cases of severe/refractory infection 
consider intravenous antibiotics. 
Consider dermatological and/or 
surgical evaluation. 
Grade 4: life-threatening 
consequences, urgent intervention 
indicated 
Discontinue erdafitinib. 
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 
 
 
 
6.1.2.6 Guidelines for Eye Exam and Toxicity Associated With Vision Changes 
The baseline ophthalmological examinations must be performed by an ophthalmologist and should 
include assessment of visual acuity, slit lamp examination, 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 ophthalmological test should be 
performed once during screening. The Amsler Grid test will also be administered by the treating 
physician or nurse as screening visit. Additional exams should be performed as clinically necessary 
based on the findings of the Amsler grid test and clinical assessment at regular intervals as deemed 
necessary by the screening ophthalmologist.  
When CSR/ retinal pigment epithelial detachments (RPED) is suspected then an OCT should be 
performed. Fluorescein angiography could be considered appropriate in conditions such as suspected 


45 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
retinal vein occlusion (RVO). It is also recommended that color fundus photos or OCT images be 
obtained and stored in the patient’s file for future reference. In patients with suspected retinal pathology 
such as CSR or RVO a consultation with a retina specialist should be considered.  
Assessment and Evaluation Plan for Subjects in a Study and New Subjects  
New subjects enrolling onto this study 
• 
Patients that are yet to be consented should have a baseline ophthalmological exam including 
fundoscopy as described, prior to the first dose of study medication.  
• 
Additionally, an Amsler grid test should be performed at the beginning of every new cycle, end of 
treatment, and at follow up visits to identify any new abnormalities (observation of wavy, broken or 
distorted lines or a blurred or missing area of vision).  
• 
If the subject is asymptomatic and the Amsler grid test is negative, then continue study medication 
at current dose and schedule.  
• 
If the subject is asymptomatic and the Amsler grid test is positive (observation of wavy, broken or 
distorted lines or a blurred or missing area of vision) then the subject should have a full 
ophthalmological exam as described, within 7 days. If this is not possible then the study drug should 
be withheld until a full ophthalmological exam is performed.  
• 
If the subject has ocular abnormalities, manage as outlined below.  
Subjects currently enrolled with no ocular symptoms  
• 
An Amsler grid test should be performed at the beginning of every new cycle, 
end of treatment and at follow up visits to identify any new abnormalities 
(observation of wavy, broken or distorted lines or a blurred or missing area 
of vision).  
• 
If the subject is asymptomatic and the Amsler grid test is negative, then 
continue study medication at the current dose and schedule.  
• 
If the subject is asymptomatic and the Amsler grid test is positive 
(observation of wavy, broken or distorted lines or a blurred or missing area 
of vision) then the subject should have a full ophthalmological exam as 
described, within 7 days. If this is not possible then the study drug should 
be withheld until a full ophthalmological exam is performed.  
Any subject with ocular symptoms  
Subjects that have ocular symptoms at any time should be managed as per the 
guidelines in Table 10 and as outlined in the current version of the 
Investigator’s Brochure.  
Additional modification to the type and or frequency of these exams could be made 
based on emerging data and/or in consultation with regulatory agencies. If and 
when such changes are made they will be communicated and incorporated into 
existing protocols.  


46 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
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Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
 
 


47 
Protocol Number: Pending 
FGFR Inhibition in DNPC 
JNJ-42756493 Erdafitinib 
PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
Table 10: 
Guidelines for Management of Eye Toxicity 
Definition 
Study Drug Management 
Symptom Management 
Asymptomatic or mild 
symptoms; clinical or 
diagnostic observations only 
Or abnormal Amsler grid test 
Refer for an ophthalmologic examination. If an 
ophthalmologic exam cannot be performed within 7 days, 
withhold treatment of erdafitinib until an examination can be 
performed. 
If there is no evidence of eye toxicity on ophthalmologic 
examination, continue erdafitinib therapy at the same dose 
level. 
If diagnosis from ophthalmologic examination is keratitis or 
retinal abnormality such as central serous retinopathy (CSR)/ 
retinal pigment epithelial detachments (RPED), withhold 
erdafitinib until signs and symptoms have resolved. 
If toxicity is reversible (complete resolution or stabilization 
and asymptomatic) in 4 weeks according to ophthalmologic 
examination, resume erdafitinib therapy at the next lower 
dose level after consultation with the medical monitor.a 
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.a 
Refer the subject for an 
ophthalmologic examination. 
For retinal pathology perform 
OCT as appropriate and 
consider referral to a retinal 
specialist for further evaluation. 
Follow specific treatment per 
the ophthalmologist’s 
recommendation. 
Moderate; minimal, local 
symptoms 
Or noninvasive intervention 
indicated; limiting age 
appropriate instrumental ADL 
Immediately withhold erdafitinib therapy. 
If there is no evidence of drug-related corneal or retinal 
pathology on ophthalmologic examination, withhold 
erdafitinib until signs and symptoms have resolved. Resume 
erdafitinib therapy at the next lower dose level. 
If diagnosis from ophthalmologic examination is keratitis or 
retinal abnormality such as CSR/RPED, withhold erdafitinib 
until signs and symptoms have resolved, stabilized, or subject 
is lost to follow-up or withdraws consent (which ever 
happens first). 
If toxicity is reversible (complete resolution or stabilization 
and asymptomatic) within 4 weeks according to 
ophthalmologic examination, resume erdafitinib therapy at 
the next lower dose level after consultation with the medical 
monitor. 
Retinal pigment epithelial detachment, if observed, should 
be monitored at approximately 2-3-week intervals until 
resolution.  
Monitor for recurrence every 1 to 2 weeks for a month and 
as clinically appropriate thereafter. If there is no recurrence, 
then re-escalation can be considered in consultation with 
the medical monitor.  
Refer subject to an 
ophthalmologist for evaluation 
with an ophthalmologic 
examination. 
For retinal pathology, perform 
OCT as appropriate and 
consider referral to a retinal 
specialist for further evaluation. 
Follow specific treatment per 
the ophthalmologist’s 
recommendation. 
Severe or medically 
significant but not immediate 
sight-threatening symptoms; 
hospitalization or prolongation 
of existing hospitalization 
indicated; disabling; limiting 
self-care ADL 
Report as a serious adverse event and immediately withhold 
erdafitinib therapy. If toxicity is not reversible, permanently 
discontinue erdafitinib. If however the toxicity is reversible 
(complete resolution or stabilization and asymptomatic) 
within 4 weeks and the subject is having clinical benefit, and 
the investigator and the Sponsor-Investigator agree that re- 
starting drug is in the best interest of the subject, then 
erdafitinib therapy may be resumed at 2 dose levels lower if 
appropriate. Monitor for recurrence using appropriate 
investigations every 1 to 2 weeks for a month and as 
clinically appropriate thereafter. For cases of recurrence 
consider permanent discontinuation. 
Refer subject to an 
ophthalmologist for evaluation 
with an ophthalmologic 
examination. 
For retinal pathology, perform 
OCT as appropriate and 
consider referral to a retinal 
specialist for further evaluation. 
Follow specific treatment per 
the ophthalmologist’s 
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Table 10: 
Guidelines for Management of Eye Toxicity 
Definition 
Study Drug Management 
Symptom Management 
Symptoms with sight- 
threatening consequences; 
urgent intervention indicated; 
blindness (20/200 or worse) in 
the affected eye 
Permanently discontinue treatment with erdafitinib . 
Report as a serious adverse event and monitor resolution of 
the event until complete resolution, stabilization or the 
subject is lost to follow-up or withdraws consent (which ever 
happens first). 
Promptly refer subject to an 
ophthalmologist for evaluation 
with an ophthalmologic 
examination. 
Follow specific treatment per 
the ophthalmologist’s 
recommendation. 
Eye toxicities should be graded according to NCI-CTCAE. 
ADL=Activities of Daily Living, OCT= Optical Coherence Tomography 
 
 
6.1.2.7 Guidelines for the Management of Dry Eye 
• 
General considerations: Avoid unnecessary exposure to sunlight, use sunglasses in bright 
light. 
• 
Prophylactic   management:   Frequent   use   of   artificial   tear   substitutes   is   strongly 
recommended. 
• 
Reactive management: 
− 
Withhold erdafitinib for Grade 3 toxicity 
− 
Artificial tear substitutes if not started, every 4 to 6 hours 
− 
Hydrating /lubricating eye gels and ointments 
− 
Severe treatment-related dry eye should be evaluated by an ophthalmologist 
 
6.2. 
Enzalutamide 
Enzalutamide is administered in capsules containing 40 mg of enzalutamide. It will be administered 
at the FDA approved dose of 160 mg (4 capsules) by mouth daily. Enzalutamide doses should be 
taken as close as possible to the same time each day. Subjects will take 4 capsules of enzalutamide 
once daily. 
 
6.2.1. 
Dose Modifications 
Patients who experience a Grade 3 or greater toxicity deemed at least possibly related to 
enzalutamide that cannot be ameliorated by the use of adequate medical intervention should have 
their treatment interrupted until the toxicity improves to a Grade 2 or lower severity. The exception 
will be non-clinically significant AEs such as hot flashes. Patients may subsequently be re-started 
on study drug, including at a reduced dose of 120 mg (3 tablets) by mouth daily will be allowed 
with approval by the sponsor-investigator. 
 
6.3. 
Abiraterone Acetate 
Abiraterone acetate is administered in 250 mg tablets. It will be administered at the FDA 
approved dose of 1000 mg (4 tablets) by mouth daily. Systemic exposure of abiraterone acetate 
is increased when administered with food, with an approximate 7- and 5-fold increase in the Cmax 
and AUC respectively when given with a low-fat meal. When given with a fatty meal, the Cmax 
and AUC increased 17- and 10-fold respectively. Given this variation, no food should be 
consumed at least 2 hours before and one hour after taking abiraterone acetate. Abiraterone 
acetate is associated with symptoms of mineralocorticoid excess, and should be taken 
concurrently with prednisone 5 mg by mouth twice daily to blunt these side effects. Abiraterone 


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acetate doses should be taken as close as possible to the same time each day. Subjects will take 4 
tablets of abiraterone acetate once daily. 
 
6.3.1. 
Dose Modifications for LFT Abnormalities Attributed to Abiraterone Acetate 
Dose modifications are provided as guidance and should not replace the investigator’s own 
clinical judgment. 
Toxicity 
Dose of abiraterone acetate 
Dose of prednisone 
Grade 1 
No change 
No change 
Grade 2 
Hold until return to Grade 1 or 
baseline, resume after discussion 
and agreement with the Sponsor- 
Investigator * 
No change 
≥Grade 3 
Discontinue 
Taper off 
*Note: Treatment will be permanently discontinued for Grade 3 toxicity lasting longer than 5 
days, or any grade toxicity that has not resolved to Grade 1 or less within 2 weeks 
 
 
6.3.2. Dose Modifications for Hypokalemia Attributed to Abiraterone Acetate 
Dose modifications are provided as guidance and should not replace the investigator’s own 
clinical judgment. 
 
Toxicity 
Dose of abiraterone acetate 
Dose of prednisone 
Grade 1 or 2 
Initiate oral potassium 
supplementation, titrate to 
≥3.5 to ≤5.0 mmol/L, maintenance 
at ≥4.0 mmol/L recommended* 
No change 
≥Grade 3 
Hold and initiate IV potassium and 
cardiac monitoring, resume only after 
discussion and approval by 
the Sponsor-Investigator * 
No change 
Recurrence ≥Grade 3, 
or Grade 4 
Discontinue 
Taper off 
*Note: Treatment will be permanently discontinued for Grade 3 toxicity lasting longer than 5 
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be allowed to resume/continue treatment if serum potassium level is maintained ≥3.5 to ≤5.0 
mmol/L with oral potassium supplementation. 
 
6.3.3. Dose Modifications for Hypertension and Edema/Fluid Retention Attributed to 
Abiraterone Acetate 
Dose modifications are provided as guidance and should not replace the investigator’s own 
clinical judgment. 
Toxicity 
Dose of abiraterone acetate 
Dose of prednisone 
Grade 1 
No change 
No change 
Grade 2 
Hold until return to Grade 1 or 
baseline, resume at full dose* 
No change 
≥Grade 3 
Hold until Grade 1 or baseline, 
resume at full dose* 
No change 
Recurrence 
≥Grade 3, or 
Grade 4 
Discontinue 
Taper off 
*Note: Treatment will be permanently discontinued for Grade 3 toxicity lasting longer than 5 
days, or any grade toxicity that has not resolved to Grade 1 or less within 2 weeks. 
 
 
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 drug 
diary (Appendix 3) will be given to the subject to record date and time of drug intake at home. 
During the course of the study, the investigator or designated study research staff will be 
responsible for providing additional instruction to reeducate any subject who is not compliant with 
the study drug schedule. 
 
8 CONCOMITANT THERAPY 
Concomitant therapies are to be recorded at the time of screening (within 30 days prior to the first 
dose of study drug), throughout the study, and up to 30 days after the last dose of study drug in the 
appropriate section of the CRF. 
 
All therapies (prescriptions or over the counter medications) continued at the start of the study or 
started during the study and different from the study drug must be documented in the concomitant 
therapy section of the CRF. Caution should be exerted for subjects taking anti-coagulant therapies. 
Frequent monitoring for international normalized ratio (INR) is allowed at the treating physician’s 
discretion. 
 
The Sponsor Investigator must be notified in advance, or as soon as possible thereafter, of any 
instances where prohibited medications are administered. 


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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 (e.g., insulin for diabetes and hormone replacement 
therapy) is acceptable. Permitted medications are to be recorded at the time of screening (within 
30 days prior to the first dose of study drug), throughout the study, and up to 30 days after the last 
dose of study drug in the appropriate section of the eCRF. 
 
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. 
• 
Documented infectious complication should be treated with oral or IV antibiotics or other 
anti-infective agents as considered appropriate by the treating investigator for a given 
infectious condition, according to standard institutional practice. 
• 
Growth factor support 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. 
• 
Palliative radiotherapy: Localized radiotherapy for symptomatic control is permitted, but 
should not include definitive radiation to target lesions. 
• 
Chronic supportive therapies: Ongoing bisphosphonates and denosumab or other supportive 
therapies are permitted.. 
 
8.2 Prohibited Medications 
The following concomitant medications are prohibited during the study. The Sponsor-Investigator 
must be notified in advance, or as soon as possible thereafter, of any instances in which prohibited 
therapies were administered. 
 
• 
Concurrent investigational agents 
• 
Medications known to increase serum levels of calcium (thiazide diuretics, vitamin A 
supplements, vitamin D supplements, calcium dietary supplements, calcium antacids, lithium, 
estrogens, anti-estrogens). Vitamin D and calcium supplements may be given if clinically 
indicated (in the setting of low serum vitamin D and calcium levels). Medications known to 
have calcium as an excipient should be avoided unless no alternatives exist. 
• 
Medications known to increase serum levels of phosphate, such as potassium phosphate 
supplements (oral or IV), vitamin D supplements, antacids, and phosphate-containing enemas 
and laxatives (oral/rectal) thought to increase serum phosphate levels. Medications known to 
have phosphate as an excipient should be avoided unless no alternatives exist. 


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8.3 Precautions for Concomitant Medications 
The following precautions are advised for subjects receiving erdafitinib: 
 
• Based on in vitro data, erdafitinib is metabolized by cytochrome CYP2C9 and CYP3A4. A 
clinical drug-drug interaction study showed that on average, erdafitinib exposure (Cmax 
and AUC) was increased 5-34% when co-administered with itraconazole (a strong 
inhibitor of CYP3A4) and 21-49% when co-administered with fluconazole (a moderate 
inhibitor of CYP2C9). For this reason, strong CYP3A4 and moderate CYP2C9 inhibitors 
should be used with caution (see Attachment 5). Consider alternative therapies that are not 
strong inhibitors of CYP3A4 or moderate inhibitors of CYP2C9 during treatment with 
erdafitinib. If co administration of these drugs is unavoidable, monitor the subject closely 
for adverse reactions and consider dose modifications accordingly. If the strong inhibitor 
of CYP3A or moderate inhibitor of CYP2C9 is discontinued, the erdafitinib dose may be 
increased in the absence of drug-related toxicity 
• The impact of moderate to strong inducers of CYP3A4 and CYP2C9 (such as rifampin) on 
erdafitinib was not clinically studied. Caution should be exercised for concomitant 
administration of erdafitinib and CYP inducers (see Attachment 5) 
• Erdafitinib was shown to inhibit, in in vitro experiments, human P-glycoprotein (P-gp) at 
concentrations achieved at therapeutic doses in humans. If the compound is administered 
with drugs that are substrates of P-gp, there is the potential for observing increased 
concentrations of the substrate drug. Therefore, caution should be exercised for co 
administered drugs that are P-gp substrates, such as digoxin, dabigatran, and fexofenadine 
(https://www.fda.gov/downloads/drugs/guidances/ucm292362.pdf); in addition, drugs with 
a narrow therapeutic index should only be used where the benefit outweighs the potential 
risk 
• For subjects taking erdafitinib: medications known to increase serum levels of phosphate, 
such as potassium phosphate supplements (oral or IV), vitamin D supplements, antacids, 
and phosphate-containing enemas and laxatives (oral/rectal) thought to increase serum 
phosphate levels. Caution should be exercised considering the risk benefit ratio, and more 
frequent monitoring of phosphate levels during treatment with medications known to 
increase the serum level of phosphate put in place 
• Concomitant use of medications that are known strong inducers of CYP3A4 is to be 
avoided with erdafitinib 
 
9 STUDY EVALUATIONS 
 
9.1 Study Procedures 
 
9.1.1 Overview 
The  Time  and  Events  Schedule  summarizes  the  frequency  and  timing  of  safety,  efficacy, 
biomarker, and other measurements applicable to this study. 
 
The number of blood samples and volume of blood that will be required from each subject for the 
various study procedures is outlined in the Laboratory Manual. The number of samples and the 
blood volume will vary depending on the number of cycles of the study drug that the subject 
receives.  Unscheduled blood samples may be required for safety issues of individual subjects 
 
The maximum research blood volume to be collected from each subject will be approximately 40 


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mL at any given timepoint. 
 
9.1.2 Screening Phase 
The Study Screening Period is 30 days before the first dose of study medication. Subjects must 
meet all of the inclusion and none of the exclusion criteria in Section 4. All information required 
for determining eligibility must be available prior to C1D1. Retesting of abnormal laboratory 
values that may lead to exclusion will be allowed once. Retesting will take place during an 
unscheduled visit in the screening phase. 
 
The following procedures will occur during the Study Screening Period: 
 
1. Comprehensive  medical  history  and  physical  exam,  including  height  and  weight, 
medications, blood pressure and heart rate 
 
2. ECOG performance status assessment 
 
3. Ophthalmic examination 
 
4. PSA (Prostate-specific antigen) 
 
5. CBC (Complete blood count) with differential 
 
6. CMP (Comprehensive Metabolic Panel - Sodium, Potassium, Chloride, BUN, Serum 
Creatinine, Calcium, Total Protein, Albumin, Total Bilirubin, AST, ALT, Alkaline 
Phosphatase, CO2) 
 
7. Serum testosterone 
 
8. Phosphate level 
 
9. PT/INR and PTT 
 
10. Radiographic assessments: CT chest/abdomen/pelvis and Bone scan 
 
11. Electrocardiogram (EKG) 
 
12. Pathologic evaluation of tumor tissue acquired at any time to assess for DNPC phenotype 
in patients who have only progressed on one AR-directed therapy and not 
previously treated with taxane chemotherapy (see 
Section 9.2.1.1). Note: 
metastatic biopsy obtained within 8 weeks of enrollment is preferred. 
 
9.1.3 Treatment Phase 
Assessments must be done within ±7 days of the specified time point unless 
indicated otherwise. All procedures are to be completed on Day 1 of each cycle 
unless otherwise noted. 
1. Comprehensive medical history and physical exam, including weight, medications, blood 
pressure and heart rate 
 
2. ECOG performance status assessment 


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3. PSA (Prostate-specific antigen) [to be completed after every 3 cycles (e.g. C4D1, C7D1, 
C10D1, etc)]. 
 
4. CBC (Complete blood count) with differential 
 
5. CMP (Comprehensive Metabolic Panel - Sodium, Potassium, Chloride, BUN, Serum 
Creatinine, Calcium, Total Protein, Albumin, Total Bilirubin, AST, ALT, Alkaline 
Phosphatase, CO2) 
 
6. Phosphate level [Day 1 of each cycle AND on C1D14 ±2 days] 
 
7. Radiographic assessments: CT chest/abdomen/pelvis and Bone scan [to be completed 
after every 3 cycles (e.g. C4D1, C7D1, C10D1, etc)]. 
 
8. Correlative blood draw [C1D1 and C4D1] 
 
 
9.1.4 End of Treatment 
Assessments must be done within ±14 days of the specified time point unless 
indicated otherwise. All procedures are to be completed on Day 1 of each cycle 
unless otherwise noted. Procedures need not be repeated if done within the past 
14 days. 
1. Comprehensive medical history and physical exam, including weight, medications, blood 
pressure and heart rate 
 
2. ECOG performance status assessment 
 
3. PSA (Prostate-specific antigen) 
 
4. CBC (Complete blood count) with differential 
 
5. CMP (Comprehensive Metabolic Panel - Sodium, Potassium, Chloride, BUN, Serum 
Creatinine, Calcium, Total Protein, Albumin, Total Bilirubin, AST, ALT, Alkaline 
Phosphatase, CO2) 
 
6. Phosphate level 
 
7. Radiographic assessments: CT chest/abdomen/pelvis and Bone scan 
 
8. Correlative blood draw 
 
9. Metastatic research biopsy. Will only be obtained if feasible (i.e. safe and amenable 
metastatic lesion). 
 
9.2 Efficacy Evaluations 
Disease assessments will be performed according to the Time and Events Schedule. Assessment 
of  responses  for  solid  tumors  will  be  performed  according  to  RECIST  (version  1.1)  by 


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investigators. For subjects who discontinue study drug before disease progression, tumor 
assessments should continue as described in Section 9.1.3. 
 
More frequent radiological assessments are allowed, if clinically indicated/desirable. Identical 
methodology 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. Patients will 
ideally undergo CT and bone scans to assess for radiographic progression; however, MRI may 
substitute the CT scan with approval of the sponsor-investigator. Ultrasound, fluorine 18- 
fluorodeoxyglucose positron emission tomography (FDG-PET), and plain x-rays are not 
acceptable methods of evaluating disease response in the absence of CT or MRI scans. 
 
If symptomatic deterioration (on the basis of global deterioration of health status) occurs without 
documentation of radiographic progression, the clinical findings used to make this determination 
must be specified in the eCRF and documented in the source documents. Every effort should be 
made to document the objective progression even after discontinuation of treatment for 
symptomatic deterioration. Tumor response will be reported by the investigator in the eCRF. 
 
9.2.1. Evaluations 
 
9.2.1.1 Pathologic Assessment 
It is well recognized that in the late stages of prostate cancer, dependency on AR-signaling is often 
lost, with ~10% tumors trans-differentiating into small cell/NE variants36,37. Recognizing the 
presence of small cell prostate cancer is imperative, as standard of care for these cases involves 
platinum-doublet chemotherapy akin to the regimens used to treat small cell lung cancer37,38. Clinical 
criteria to identify these cases, include: visceral metastases only, predominately lytic bone lesions, 
bulky lymphadenopathy, bulky high-grade prostatic or pelvic mass, low PSA level, 
neuroendocrine markers in serum and short interval to developing CRPC36,37. Given that many 
of these clinical features are expected to overlap with those of DNPC, it is recommended that 
the treating physician obtain a standard of care metastatic biopsy prior to enrollment to rule out 
predominate small cell/NE prostate cancer. 
 
Pathologic assessment during screening will involve IHC for AR or proteins that are regulated 
by AR-signaling (e.g. PSA, NKX3.1, etc.) and a NE marker (e.g. synaptophysin, INSM1, 
chromogranin, etc.). We will utilize a composite score for AR/AR regulated proteins and NE 
marker expression to define DNPC. This composite score will be calculated as follows: 
 
AR/AR regulated protein or NE marker composite expression score = (Percentage of nuclear 
AR/AR regulated protein or NE marker positive cells) x (Intensity of staining, where 1=low 
intensity, 2=moderate intensity and 3=high intensity) 
 
We will define AR/AR regulated protein negative as a score <40 and NE marker negative as a 
score <10. These cutoffs were selected based on prior experience from our rapid autopsy program. 
Of 73 AR+ cases, only 3 had AR composite expression scores <40. Similarly, 0 of 5 NE/small 
cell cases had synaptophysin scores <10. These cut offs were selected to avoid being overly 
stringent in defining the study population given that we have observed heterogeneity across tumors 
from rapid autopsy patients, with at least one case demonstrating a NE tumor in one location 
and a DNPC in the other24. Patients with evidence of small cell morphology on biopsy will be 
excluded. 
 


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Transcript profiling methods for identifying DNPC may also be accepted for determining trial 
eligibility at the PI’s discretion. This is based on data showing that transcriptional signatures can 
accurately define the various prostate cancer subtypes, including DNPC5,39. 
 
Given that intra/inter-tumoral phenotypic heterogeneity is increasingly recognized in late stage 
prostate cancer, and that FGFR inhibition plays an important role in mediating lineage plasticity 
in this clinical context, we will not require histologic confirmation of DNPC in late stage prostate 
cancer19-22. Patients who have previously progressed on two next-generation AR-directed therapies 
(e.g. abiraterone, enzalutamide) AND at least one prior taxane will not be required to undergo 
histologic assessment to determine eligibility. However, metastatic biopsy should be performed if 
there is clinical suspicion for a small cell/NE variant as outlined above.  
 
9.2.1.2. RECIST Assessment of Disease 
RECIST 1.1 is an accepted methodology by regulatory authorities. RECIST 1.1 will be applied by 
the investigator as the primary measure for assessment of tumor response, date of disease 
progression, and as a basis for all protocol guidelines related to disease status (e.g., discontinuation 
of study therapy). 
 
After screening, imaging will be repeated during the study as indicated in the Time and Events 
Schedule. 
 
9.2.1.3. Radiographic Images Assessment 
Bone scan and Computed tomography (CT) scans of the chest, abdomen, pelvis, and any other 
location where disease is present will be performed at Screening. During the study, disease 
response will be assessed using bone scan and CT scans of the locations of known disease. 
Magnetic resonance imaging may be used to evaluate sites of disease that cannot be adequately 
imaged using CT (in cases where MRI is desirable, the MRI must be obtained at baseline and at 
all subsequent response evaluations or in cases where use of CT scan is clinically contraindicated). 
For all other sites of disease, MRI studies do not replace the required chest, abdomen, and pelvic 
CT scans. Brain MRI and lumbar puncture are required, only if clinically indicated. 
 
Imaging should not be delayed due to delays in cycle starts or extension of cycle intervals. After 
disease progression is documented, subjects will be monitored as outlined in Section 9.1.4. 
 
If the site study team makes an initial assessment of disease progression, and if the subject is 
clinically stable, treatment may be continued if the investigator and sponsor-investigator 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 study treatments until such time as the treating physician 
and the sponsor-investigator agree that further continuation of treatment is no longer beneficial to 
the subject or he has completed two years of treatment total, whichever comes first. 
 
9.3. 
Correlative research 
This study will also include a number of correlative studies aimed at identifying candidate 
biomarkers for response/resistance to FGFR inhibitor therapy. We will evaluate pre- and post- 
treatment tissue as well as serial blood samples in order to develop blood-based biomarkers for 
response/resistance to erdafitinib. Baseline protein and transcript expression, as well as changes 
in these parameters with treatment will be correlated with clinical outcomes. This information 
will be used to develop a gene expression response-signature, which we will be assessed in 


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blood samples. 
 
Biospecimen samples (e.g., blood, tumor tissue) will be stored for up to five years following the 
completion of this study and any unused samples will be destroyed at the end of this time period. 
Samples will be stored at University of Washington and/or Fred Hutchinson Cancer Research 
Center, and the Sponsor-Investigator will oversee access to biospecimens. In order to protect the 
identity of study subjects, all biospecimen samples will be labeled with a subject-specific study 
ID code. Samples will be analyzed at University of Washington and/or Fred Hutchinson Cancer 
Research Institute. Biospecimens will used for research pertaining to this clinical study only. 
 
Next-generation sequencing 
Patients will undergo next-generation sequencing (NGS) using UW-OncoPlex, a comprehensive 
whole gene NGS panel that has been validated for use on tumor tissue and cell-free circulating 
tumor DNA (ctDNA)40. A research-based sequencing assay may also be utilized in order to 
evaluate for mutations in genes not covered by UW-OncoPlex. Sequencing studies will be 
prioritized for patients that have demonstrated a clinical response to treatment. 
 
Transcript profiling studies 
 
Transcript profiling studies (e.g. RNA-seq, NanoString) will be performed on metastatic biopsies 
to assess activation of the core AR-, MAPK- and FGF/FGFR-signaling programs, and to identify 
unknown pathways involved in mediating response/resistance to treatment41,42. We may also 
perform circulating tumor cell (CTC)-based transcript profiling studies using AdnaTest and 
multiplex qPCR or another blood-based transcript profiling assay.. 
 
Protein expression studies 
 
Protein expression studies at baseline and at the time of progression, including IHC for AR, PSA, 
phospho-FRS2 (a downstream target of the FGF8 cognate receptors: FGFR1IIIc and FGFR2IIIc) 
and phosphor-FGFR. Additional protein expression studies may be added depending on the results 
of NGS and transcript profiling studies. 
 
9.4. 
Safety Evaluations 
Safety assessments will be based on medical review of adverse event reports and the results of 
vital sign measurements, physical examinations, clinical laboratory tests, ECOG performance 
status, ophthalmic examinations, and other safety evaluations at specified time points as described 
in the Time and Events Schedule. 
 
Any clinically significant abnormalities or toxicities persisting at the end of the study will be 
followed by the investigator until resolution or until reaching a clinically stable endpoint. For 
adverse events such as skin/nail and mucosal toxicity, upon subject consent, photographs may be 
taken for assessment and monitoring of the toxicity. 
 
9.4.1. 
Adverse Events 
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or 
the subject's legally acceptable representative) for the duration of the study. The incidence of 
adverse events will be tabulated and reviewed for potential significance and clinical importance. 
Adverse events will be graded according the NCI-CTCAE, Version 4.0. Adverse events will be 


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followed by the investigator as specified in Section 11, Adverse Event Reporting. 
 
9.4.2. 
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology will be collected according to the Time and 
Events Schedule. More frequent clinical laboratory tests may be performed, as indicated by the 
overall clinical condition of the subject and for abnormalities that warrant more frequent 
monitoring. 
 
The investigator must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the adverse event section of the eCRF. Laboratory 
test results completed on Cycle 1 Day 1 should be reviewed prior to dosing and subjects should 
continue to meet eligibility requirements per the Inclusion/Exclusion criteria. 
 
The following tests will be performed: 
 
Complete Blood Count 
-hemoglobin 
-platelet count 
-white blood cell (WBC) count and differential 
 
Serum Chemistry Panel 
 
-sodium 
-chloride 
-blood urea nitrogen 
-glucose 
-potassium 
-bicarbonate (CO2) 
-creatinine 
-phosphate 
-albumin 
-total protein 
-alanine aminotransferase (ALT) 
-direct bilirubin 
-aspartate aminotransferase (AST) 
-total bilirubin 
-alkaline phosphatase 
 
 
9.4.3. 
Renal Toxicity Evaluation 
Creatinine or creatinine clearance will be determined per institutional standard. 
 
9.4.4. 
Electrocardiogram 
Screening electrocardiograms, to be used to determine subject eligibility, will be performed at the 
study site. 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 should be produced and stored in 
the subject’s source documents. The 12-lead ECG recorder device used should have been recently 
serviced and calibrated. The following variables should be measured: heart rate, RR, QT, PR, QRS, 
QTc (Fridericia) intervals. QTcF (Fridericia) will be used for assessment of QTc interval. The 
investigator will comment on the clinical relevance and document this in the eCRF (along with 
details of clinically significant findings). 
 
9.4.5. 
Ophthalmic Examination 
All subjects should have an ophthalmological examination performed at Screening by an 


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Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
ophthalmologist, which should include assessment of visual acuity, tonometry, fundoscopy 
(examination of both central and peripheral zones should be performed) and an Amsler Grid test; 
where available, an Optical Coherence Tomography (OCT) should be performed. A follow-up 
examination should be performed as clinically necessary based on the findings of the Amsler grid 
tests and clinical assessment. 
 
When Central Serous Retinopathy (CSR)/Retinal Pigment Epithelial Detachments (RPED) is 
suspected, an OCT should be performed. Fluorescein angiography could be considered appropriate 
in conditions such as suspected Retinal Vein Occlusion (RVO). It is also recommended that color 


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fundus photos or OCT images be obtained and stored in the subject’s records for future reference. 
In subjects with suspected retinal pathology such as CSR or RVO, a consultation with a retina 
specialist should be considered. 
 
Amsler grid testing will be administered by the treating physician or nurse at timepoints according 
to the Time and Events Schedule. Observation of wavy, broken or distorted lines, or a 
blurred/missing area of vision is equivalent to a positive Amsler grid test. For any positive Amsler 
grid test, subject should be referred for full ophthalmologic exam within 7 days. However, if the 
subject has an abnormal Amsler grid test 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. 
 
9.4.6. 
Vital Signs 
Blood pressure (systolic and diastolic), heart rate, and oral or tympanic temperature will be 
assessed. Abnormalities will be recorded as AEs 
 
9.4.7. 
Physical Examination 
A full physical examination, including height, and weight will be performed at screening. Targeted 
physical examinations of involved organs, and including weight, will be performed at subsequent 
visits as listed in the Time and Events Schedule. New abnormalities will be recorded as AEs. 
 
9.4.8. 
ECOG Performance Status 
Eastern Cooperative Oncology Group performance status score will be determined at pre-specified 
time points listed in the Time and Events Schedule. Eastern Cooperative Oncology Group scoring 
information is provided in Appendix 1. 
 
9.5.      Sample Collection and Handling 
The actual dates and times of sample collection must be recorded in the laboratory requisition 
form/source documentation. Refer to the Time and Events Schedules for the timing and frequency 
of all sample collections. 
 
Instructions for the collection, handling, and shipment of samples are found in the Laboratory 
Manual. 
 
10 SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY 
 
10.1. Completion 
A subject will be considered as having completed the study if he or she has died during the study 
or has not been withdrawn from the study by the end of the study. 


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10.2 Discontinuation of Study Treatment/Withdrawal from the Study 
 
Discontinuation of Study Treatment 
A subject who discontinues study treatment will continue to participate in the study for follow-up 
of survival status, resolution of any ongoing AEs, and disease assessments if treatment 
discontinuation occurs before disease progression. 
 
A subject's study treatment must be discontinued if: 
 
• 
The investigator believes that for safety reasons or tolerability reasons (e.g., adverse event) it 
is in the best interest of the subject to discontinue study treatment 
• 
Disease progression 
− 
Exception: if the investigator and sponsor-investigator agree that continuation of 
treatment is in the best interest of the subject considering the terminal nature of the 
underlying disease, he may receive erdafitinib until such time as the treating physician 
and the sponsor-investigator agree that further continuation of treatment is no longer 
beneficial to the subject. 
• 
The subject refuses further treatment with the study drug 
• 
The Sponsor-Investigator terminates the study 
• 
Investigator decision approved by the sponsor 
If a subject discontinues treatment, an End-of-Treatment visit should be conducted within 30 days 
of the subject’s last dose of study drug. The primary reason for treatment discontinuation will be 
clearly documented in the subject’s medical record and recorded in the eCRF. Once a subject 
discontinues treatment with the study drug, the subject will not be permitted to be retreated. 
 
If a subject discontinues study treatment for any reason before the end of the treatment phase, post- 
treatment 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 discontinues study drug and withdraws from the study before the end of the treatment 
period, all post-treatment assessments should be obtained. 
 
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 consent before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. In addition, subjects who withdraw consent 
must complete and sign a withdrawal of consent form to specify if they agree to have survival data 
collected or not. Study drug assigned to the withdrawn subject may not be assigned to another 


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subject. Subjects may be replaced only if the subject withdrew prior to the study drug 
administration. 
 
10.3. Withdrawal From the Use of Research Samples 
The subject may withdraw consent for use of samples for 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 main ICF. 
 
11 DATA MONITORING AND ADVERSE EVENT REPORTING 
Institutional support of trial monitoring will be in accordance with the FHCRC/University of 
Washington Cancer Consortium Institutional Data and Safety Monitoring Plan. Under the 
provisions of this plan, FHCRC Clinical Research Support coordinates data and compliance 
monitoring conducted by consultants, contract research organizations, or FHCRC employees 
unaffiliated with the conduct of the study. Independent monitoring visits occur at specified 
intervals determined by the assessed risk level of the study and the findings of previous visits per 
the institutional DSMP. 
 
In addition, protocols are reviewed at least annually and as needed by the Consortium Data and 
Safety Monitoring Committee (DSMC), FHCRC Scientific Review Committee (SRC) and the 
FHCRC/University of Washington Cancer Consortium Institutional Review Board (IRB). The 
review committees evaluate accrual, adverse events, stopping rules, and adherence to the 
applicable data and safety monitoring plan for studies actively enrolling or treating patients. The 
IRB reviews the study progress and safety information to assess continued acceptability of the 
risk-benefit ratio for human subjects. Approval of committees as applicable is necessary to 
continue the study. 
 
The trial will comply with the standard guidelines set forth by these regulatory committees and 
other institutional, state and federal guidelines. 
 
Additionally, scheduled meetings will take place weekly and will include the Sponsor Investigator 
(Michael Schweizer, MD), research nurse, data manager, and, when appropriate, the collaborators, 
sub-investigators, and biostatistician involved with the conduct of the protocol. 
 
During these meetings the investigators will discuss matters related to: safety of protocol 
participants, validity and integrity of the data, enrollment rate relative to expectation, 
characteristics of participants, retention of participants, adherence to protocol (potential or real 
protocol violations), data completeness, and progress of data for secondary objectives. 
 
If ≥3 out of the first 10 subjects enrolled are removed from the study due to a safety issue, the trial 
will terminate prematurely. Depending on the number of patients removed from the study due to 
safety issues, study accrual may have to be put on hold until the 10th subject has completed at least 
one treatment cycle. For example, if 2 subjects were removed for safety reasons prior to accruing 
the 10th subject, accrual would not continue until the 10th subject completes the first cycle. Safety 
issues will be continually monitored and safety oversight will be provided through the weekly 
meetings between the PI and relevant staff. 


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11.1 Management of Safety Data 
As the Sponsor-Investigator of the Study, Dr. Michael T. Schweizer shall be solely responsible 
for complying with required timelines, any safety-reporting obligation to competent Health 
Authorities, IRB/ECs and any participating (co or sub) investigators, as defined in applicable 
laws and regulations. 
 
This Study has been designated as an interventional study.  As such, all adverse events, special 
situations including pregnancies and product quality complaints will be reported from the time a 
subject has signed and dated an Informed Consent Form (ICF) until 30 days after the last 
documented use of the product under study within the study. All subsequent AEs and SAEs will 
be collected after this period if the Principal Investigator considers the AE/SAE to be causally-
related to the use of the study drug. 
 
For the purposes of this study, the J&J medicinal product(s) are: Balversa (erdafitinib (JNJ-
42756493) and Zytiga (abiraterone acetate).  
 
11.2 Definitions 
Adverse Event (AE) 
 
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 
and unintended sign (including an abnormal finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational or 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. 
 
Adverse Events of Special Interest 
 
Adverse events of special interest are events that Janssen Research & Development is actively 
monitoring as a result of a previously identified signal (even if non-serious). 
 
For erdafitinib, the adverse events of special interest are: 
 
• 
Central Serous Retinopathy: including PTs of retinal detachment, chorioretinopathy, 
detachment of retinal pigment epithelium, retinopathy, vitreous detachment, retinal 
edema, detachment of macular retinal pigment epithelium 
 
There are no adverse events of special interest for abiraterone acetate. 
 
 
Individual Case Safety Report (ICSR) 
 
A valid ICSR must contain the four minimum criteria required to meet regulatory reporting 


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requirements. 
• an identifiable subject (but not disclosing personal information such as 
the subject’s name, initials or address) 
 
• an identifiable reporter (investigational site) 
 
• The name of the investigational product (i.e. erdafitinib, abiraterone 
acetate and/or enzalutamide) 
 
• an adverse event, outcome, or certain special situations 
The minimum information required is: 
• date of therapy (start and end date, if available) 
 
• batch or lot number, if available 
 
• Suspected J&J medicinal product (doses, indication) 
 
• subject details (subject ID and country) 
 
• age at AE onset 
 
• reporter ID 
 
• adverse event detail (AE verbatim in English), onset date, relatedness, causality, 
action taken, outcome, (if available) 
 
• J&J protocol ID 
 
Adverse Drug Reaction (ADR) 
 
A noxious and unintended response to any dose of the drug (or biological) product for which there 
is a reasonable possibility that the product cause the response. ‘‘Reasonable possibility’’ means 
there is evidence to suggest a causal relationship between the drug and the adverse event. 
Suspected adverse reaction implies a lesser degree of certainty about causality than adverse 
reaction, which means any adverse event caused by a drug. 
 
Product Quality Complaint (PQC) 
 
A product quality compliant is defined as any suspicion of a product defect related to a potential 
quality issue during manufacturing, packaging, release testing, stability monitoring, dose 
preparation, storage or distribution of the product, or delivery system. Not all PQCs involve a 
subject. Lot and batch numbers are of high significance and need to be collected whenever 
available. 
 
Examples of PQC include but not limited to: 
 
• Functional Problem: e.g., altered delivery rate in a controlled release product 


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• Physical Defect:  e.g. abnormal odor, broken or crushed tablets 
 
• Potential  Dosing  Device  Malfunction:  e.g.,  auto-injector  button  not  working, 
needle detaching from syringe 
 
• Suspected Contamination 
 
• Suspected Counterfeit 
 
Serious Adverse Event (SAE) 
 
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose: 
 
• Results in death 
 
• Is life-threatening 
 
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.) 
 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
 
• Results in persistent or significant disability/incapacity 
 
• Is a congenital anomaly/birth defect 
 
• Is a suspected transmission of any infectious agent via a medicinal product 
 
• Is medically important* 
 
*Medical and scientific judgment should be exercised in deciding whether 
expedited reporting is also appropriate in other situations, such as important 
medical events that may not be immediately life threatening or result in death or 
hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the other outcomes listed in the definition above. These should 
usually be considered serious. 
 
NOTE:  DEATH  FOR  ANY  REASON  SHOULD  BE  REPORTED  AS  A  SERIOUS 
ADVERSE EVENT. 
 
Hospitalization 
 
For reports of hospitalization, it is the sign, symptom or diagnosis which led to the hospitalization 
that is the serious event for which details must be provided. 
 
Any event requiring hospitalization or prolongation of hospitalization that occurs during the study 
must be reported as a serious adverse event, except hospitalizations for the following: 


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• Hospitalizations not intended to treat an acute illness or adverse event (e.g., social 
reasons such as pending placement in long-term care facility) 
 
• Surgery or procedure planned before entry into the study. [Note: Hospitalizations 
that were planned before the start of data collection and where the underlying 
condition for which the hospitalization was planned has not worsened will not be 
considered serious adverse events. Any adverse event that results in a prolongation 
of the originally planned hospitalization is to be reported as a new serious adverse 
event.] 
 
Life-Threatening Conditions 
 
The cause of death of a subject in a study within 30-days of the last dose of one or more of the 
Study Drugs, whether or not the event is expected or associated with the study drug, is considered 
a serious adverse event. 
 
Disease progression should not be recorded as an adverse event or serious adverse event term; 
instead, signs and symptoms of clinical sequelae resulting from disease progression/lack of 
efficacy will be reported if they fulfill the serious adverse event definition. 
 
Unlisted (Unexpected) Adverse Event/Reference Safety Information 
 
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For a medicinal product(s) with a marketing authorization, 
the expectedness of an adverse event will be determined by whether or not it is listed in the 
applicable product information. 
 
For erdafitinib, the expectedness of an adverse event will be determined by whether or not it is 
listed in Section 6 of the Investigator's Brochure (reference safety information for assessment of 
expectedness of serious adverse reactions). 
 
For abiraterone acetate, the expectedness of an adverse event will be determined by whether or not 
it is listed in the FDA prescribing information. 
 
https://www.zytiga.com/ 
 
https://www.balversa.com/  
 
For Balversa™ (erdafitinib) and Zytiga™ (abiraterone acetate), the expectedness of an adverse event 
will be determined by whether or not it is listed in the Investigator's Brochure 
 
Special Reporting Situations 
 
Safety events of interest for a J&J medicinal product that require expediting reporting and/or 
safety evaluation include, but are not limited to: 
• Drug exposure during pregnancy (maternal and paternal) 
• Overdose of a J&J medicinal product 
• Exposure to a J&J medicinal product from breastfeeding 
• Suspected abuse/misuse of a J&J medicinal product 


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• Inadvertent or accidental exposure to a J&J medicinal product 
• Any failure of expected pharmacological action (i.e., lack of effect) of a J&J medicinal 
product  
• Medication error (includes potential, intercepted or actual) involving a J&J 
medicinal product (with or without patient exposure to the J&J medicinal 
product(s) under study, e.g., name confusion) 
• Suspected transmission of any infectious agent via administration of a medicinal 
product 
 
• Unexpected therapeutic or clinical benefit from use of a J&J   medicinal product 
 
These safety events may not meet the definition of an adverse event; however, from a 
Janssen Research & Development  perspective, they are treated in the same manner as 
adverse events. Special situations should be recorded on the Adverse Event page of the 
CRF. 
 
Any special situation that meets the criteria of a serious adverse event should be recorded 
on a Serious Adverse Event Report Form and be reported to Janssen Research & 
Development within 24 hours of becoming aware of the event. 
 
 
11.3 Pregnancy 
Erdafitinib is developed as an anticancer agent. There are no reproductive or developmental 
toxicology data available for erdafitinib. There may be unforeseeable risks to the embryo or 
fetus. Subjects (with a partner of child-bearing potential) must use medically acceptable methods 
of birth control prior to study entry and for the duration of the study, and for at least 3 months 
after the last intake of study drug. Subjects must use a condom with spermicide when sexually 
active and must not donate sperm from the first dose of study drug until 3 months after the last 
dose of study drug. Medically acceptable methods of contraception that may be used by the 
subject and/or his partner include hormonal prescription oral contraceptives, contraceptive 
injections, contraceptive patch, intrauterine device, true sexual abstinence, and surgical 
sterilization (e.g., confirmed successful vasectomy or tubal ligation). True sexual abstinence is an 
acceptable method of contraception and is defined as refraining from heterosexual intercourse 
during the entire period of the study, including up to 3 months after the last dose of study drug is 
given. Periodic abstinence (calendar, symptothermal, postovulation methods) is not considered 
an acceptable contraceptive method. 
 
Because the study drug may have an effect on sperm, pregnancies in partners of male subjects 
included in the study must be reported by the Sponsor-Investigator within 24 hours to  of their 
knowledge of the event using the Serious Adverse Event Form. All pregnancies must be reported 
from the time of informed consent and 90 days following last dose. Depending on local 
legislation this may require prior consent of the partner. Follow-up information regarding the 
outcome of the pregnancy and any postnatal sequelae in the infant will be required. 
 
11.4. Adverse Event Monitoring and Reporting 
The Sponsor Investigator, Sub-Investigators, and/or the research nurse will monitor each patient 
closely for the development of adverse events and toxicities and record all such events. Patients 


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will be evaluated for toxicity if they have received one dose of any of the Study Drugs. The timely 
reporting of adverse events (including toxic deaths) is required by the Food and Drug 
Administration (FDA). 
 
In general, the Sponsor-Investigator must immediately report (i.e. within 24 hours) to Janssen 
Research & Development any serious adverse event and Special Reporting Situations, whether or 
not considered drug related. Study endpoints that are serious adverse events (e.g., all-cause 
mortality) must be reported in accordance with the protocol unless there is evidence suggesting a 
causal relationship between the drug and the event (e.g., death as a result of anaphylactic reaction 
or fatal hepatic necrosis). In that case, the investigator must immediately report the event to 
Janssen Research & Development. The sponsor must record non-serious adverse events and report 
them to Janssen Research & Development according to the timetable outlined in the Research 
Funding Agreement section entitled Reporting of Data and to fulfill regulatory reporting 
requirements. 
 
For each subject, AEs, SAEs, Adverse Events of Special Interest and Special Reporting Situations 
should be recorded after informed consent is obtained until the subject has completed participation 
in the study as follows: 
 
A Serious Adverse event must be reported if it occurs during a subject’s participation in the Study 
(whether receiving Study Product or not) and within 30 days of receiving the last dose of Study 
Product. 
 
Any serious adverse event that is ongoing when a subject completes his/her participation in the 
Study must be followed until any of the following occurs: 
 
• the event resolves or stabilizes; 
 
• the event returns to baseline condition or value (if a baseline value is available); 
 
• the event can be attributed to agents(s) other than the Study Product, or to factors 
unrelated to Study conduct. 
 
11.5. Procedures for Reporting Safety and Data and Product Quality Complaints 
(PQCs) for J&J Medicinal Products to the Company 
All adverse events, whether serious or non-serious, related or not related, following 
exposure to study drugs are to be documented by the investigator and recorded in the CRF 
and in the subject’s source records. Investigators must record in the CRF their opinion 
concerning the relationship of the adverse event to the study drugs. 
 
All (serious and non-serious) adverse events reported for the study drugs should be 
followed up- in accordance with clinical practice. 
 
 
11.5.1. Serious Adverse Events (SAE), Adverse Events of Special Interest, and 
Special Reporting Situations 
All serious adverse events that have not resolved by the end of the study, or that 
have not resolved upon discontinuation of the subject's participation in the study, 


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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) 
The Sponsor Investigator will transmit all SAEs, Adverse Events of Special 
Interest and special situations following exposure to the Study Drugs in a form 
provided by the Janssen Research & Development within 24-hours of becoming 
aware of the event(s). 
All follow-up information for serious adverse events that are not resolved at the 
end of the study or by the time of patient withdrawal must be reported directly by 
the Sponsor Investigator, within 24 hours becoming aware, to Janssen Research 
& Development using their Serious Adverse Event Report 
All available clinical information relevant to the evaluation of a related SAE, 
Adverse Events of Special Interest, serious ADR or special situation is required. 
• The Sponsor Investigator is responsible for ensuring that these cases are 
complete and if not are promptly followed-up. A safety report is not 
considered complete until all clinical details needed to interpret the case 
are received. Reporting of follow-up information should follow the same 
timeline as initial reports. 
• Copies of any and all relevant correspondences with regulatory authorities 
and ethics committees regarding any and all serious adverse events, 
irrespective of association with the Study Drugs, are to be provided to the 
Janssen Research & Development within 24 hours of such report or 
correspondence being sent to applicable health authorities. 
 
11.5.2. Product Quality Complaints Reporting 
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 patients, investigators, and  Janssen Research & 
Development, and are mandated by regulatory agencies worldwide.  Janssen 
Research & Development has established procedures in conformity with 
regulatory requirements worldwide to ensure appropriate reporting of PQC 
information. Lot and/or Batch #s shall be collected or any reports failure of 
expected pharmacological action (i.e., lack of effect). The product should be 


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quarantined immediately and if possible, take a picture. 
 
All initial PQCs involving J&J medicinal product(s) under study  must be reported 
to Janssen Research & Development by the Sponsor Investigator within 24 
hours after being made aware of the event. The J&J contact will provide 
additional information/form to be completed. 
 
If the defect for the Lot and/or Batch of the J&J medicinal product(s) under 
study is combined with either a serious adverse event or non-serious adverse 
event, the Sponsor Investigator must report the PQC to Janssen Research & 
Development according to the serious adverse event reporting timelines.  A 
sample of the suspected product should be maintained for further investigation if 
requested by Janssen Research & Development. 
 
For SAEs, special reporting situations and PQCs following exposure to a non- 
J&J medicinal product under study, the Sponsor Investigator should notify the 
appropriate regulatory/competent authority or the manufacturer of that medicinal 
product (in the absence of appropriate local legislation) as soon as possible. 
 
11.6. 
Evaluating Adverse Events 
The grade and severity of the event will be determined using the DCT/NCI Common 
Terminology Criteria, CTCAE v.5.0 (Appendix 2). All appropriate treatment areas 
should have access to a copy of the CTCAE version 5.0. Study staff must use one of the 
CTCAE criteria to define the event. Adverse events not included in the CTCAE v.5.0 
should be reported and graded under the “Other” adverse event within the appropriate 
category and grade 1 to 5 according to the general grade definitions, mild, moderate, 
severe, life-threatening, fatal or disabling, as provided in the CTCAE. 
 
The event will be determined to be expected or unexpected. The determination of 
whether an AE is expected is based on agent-specific adverse event information 
provided in the Investigators Brochure (erdafitinib) or the FDA Prescribing Information 
(abiraterone acetate and enzalutamide). Unexpected AEs are those not listed in the 
agent-specific adverse event information. 
 
The event will be evaluated for relationship to the medical treatment or procedure. The 
Investigator should document his/her opinion of the relationship of the event to study 
medication as follows: 
 
• Unrelated- The adverse event is clearly not related to the investigational 
agent(s). 
• Unlikely- The adverse event is doubtfully related to the investigational 
agent(s). 
• Possible-The adverse event may be related to the investigational agent(s). 


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• Probable-The adverse event is most likely related to the investigational 
agent(s). 
• Definite- The adverse event is clearly related to the investigational agent(s). 
 
Based on this information, a decision will be made whether an adverse event should be 
reported as an expedited report (Serious Adverse Event) in addition to the routinely 
reported clinical data. All expedited adverse event reports that meet reporting criteria per 
institutional requirements should be submitted to the Institutional Review Board (IRB) 
and to the FDA. Additionally, all SAEs should be submitted to Janssen Research & 
Development within 24 hours of becoming aware of event and via secure e-mail. 
 
11.6.1. 
Documenting Adverse Events 
Each individual sign or symptom must be documented separately. Worksheets 
must be signed and dated by person conducting evaluation to be used as source 
documentation. The attribution of all adverse events must be verified by an 
investigator. Evaluation of laboratory toxicities may be documented directly on a 
printed laboratory report or CRF provided it is signed by the investigator. 
However, if an action was conducted due to this abnormality (e.g. RBC 
transfusion due to low Hgb) this would be recorded on the AE form also. 
Recording should be done in a concise manner using standard, acceptable medical 
terms. 
 
The adverse event recorded should not be a procedure or a clinical measurement 
(i.e. a laboratory value or vital sign) but should reflect the reason for the 
procedure or the diagnosis based on the abnormal measurement. 
Preexisting conditions that worsen in severity or frequency during the Study 
should also be recorded (a preexisting condition that does not worsen is not an 
adverse event). 
 
Further, a procedure or surgery is not an adverse event; rather, the event leading 
to the procedure or surgery is considered an adverse event. Any event requiring 
in-patient hospitalization that occurs during the course of a subject’s participation 
in a trial must be reported as an SAE. Hospitalizations that do not meet the criteria 
for SAE reporting are: 
 
A. Reasons described in the Protocol, e.g. drug administration, Protocol- 
required testing 
B. Surgery or procedure planned prior to entry into the Study. 
 
If, in the Sponsor Investigator’s judgment, a clinical significant worsening from 
baseline is observed in any laboratory or other test parameter (e.g. 
electrocardiogram (ECG), angiogram), physical exam finding, or vital sign, a 
corresponding clinical adverse event should be recorded. 
 
If a specific medical diagnosis has been made, that diagnosis or syndrome should 
be recorded as the adverse event, whenever possible.  However, a complete 
description of the signs, symptoms and investigations which led to the diagnosis 


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should be provided. For example, if clinically significant elevations of liver 
function tests are known to be secondary to hepatitis, “hepatitis” and not 
“elevated liver function tests” should be recorded. If the cause is not known, the 
abnormal test or finding should be recorded as an adverse event, using appropriate 
medical terminology (e/g/ thrombocytopenia, peripheral edema, QT 
prolongation). 
 
11.6.2. 
Maintenance of Safety Information 
All safety data should be maintained in a clinical database in a retrievable format. 
The Sponsor Investigator shall provide all adverse events, both serious and non- 
serious, in report format. However, in certain circumstances more frequent 
provision of safety data may be necessary, e.g. to fulfill a regulatory request, and 
as such the data shall be made available within a reasonable timeframe at Janssen 
Scientific Affairs’ request. 
 
11.6.3. 
SAEs Listing 
At a minimum, on a semi-annual basis and at the end of the Study, Janssen 
Research & Development  will provide to the Sponsor Investigator a listing of all 
SAEs reported to the Janssen Research & Development.  The Sponsor Investigator 
will review this listing and will resolve any discrepancies with the data provided 
by Janssen Research & Development. 
 
11.7. 
IRB Reporting 
The Sponsor Investigator is responsible to report serious adverse events and protocol 
problems (e.g. protocol deviations, non-adherence) to the FHCRC/University of 
Washington Cancer Consortium Institutional Review Board (IRB). Adverse events 
(AEs) that are unexpected, possibly related to the study drug, and serious or suggest a 
risk of greater harm from the research than previously known will be reported to the IRB 
per institutional policy. 
 
In addition, all safety data must be submitted to Janssen Research & Development. The 
following methods are acceptable for transmission of safety information to Janssen 
Research & Development.: 
 
• Electronically via J&J SECURE Email service (preferred) 
• For business purposes, if SECURE Email is non-functional: 
o Facsimile (fax), receipt of which is evidences in a successful fax 
transmission report 
o Telephone (if fax is non-functional) 
Contact information for Janssen Research & Development is below: 
 
SAE email: IIS-BIO-VIRO-GCO@its.jnj.com 
SAE fax: 1-866-651-0219 


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Follow-up reports must be submitted in a timely fashion as additional information 
becomes available.  The initial SAE report should be updated with the pertinent follow 
up information. 
 
11.8. 
Protocol Amendments 
Any changes to the protocol will be made in the form of an amendment and must be 
approved by the IRB before implementation. Changes to the protocol or informed 
consent will be reviewed and approved by Janssen Research & Development prior to 
submitting to the IRB for approval. 
 
11.9. 
Informed Consent 
Written informed consent will be obtained by a study investigator working on this study. 
An explanation of the nature of study, its purpose, procedures involved, expected 
duration, potential risks and benefits will be provided to each participant by the 
investigator or the research nurse. Each participant will be informed that participation in 
the study is voluntary and that he may withdraw from the study at any time, and that 
withdrawal of consent will not affect his subsequent medical treatment. Participants will 
be allowed time needed to make an informed decision. Participants will be encouraged 
to ask questions about the study and the consent before signing the consent form. 
Original signed consent forms will be filed in each patient’s research chart, while each 
patient will receive a copy of the consent document. No patient will enter the study 
before his informed consent has been obtained. 
 
 
12 STATISTICAL METHODS 
 
Statistical analysis will be done by the sponsor investigator or under the authority of the 
Sponsor- Investigator. A general description of the statistical methods to be used to analyze the 
efficacy and safety data is outlined below. 
 
The primary objective will be to determine the objective tumor response rate in subjects with 
measurable lesions as defined by RECIST v1.1 criteria in mCRPC patients with DNPC receiving 
either enzalutamide or abiraterone acetate.  Key secondary objectives will include determining: 
radiographic progression free survival (PFS) in patients using RECIST 1.1 criteria for soft tissue 
metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases; time to 
response using RECIST 1.1 criteria; overall survival (OS) defined as the time interval from 
C1D1 to the date of death; PSA response, defined as >50% reduction in PSA compared with 
baseline at any point during treatment; and the incidence and severity of adverse events 
according to National Cancer Institute-Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.02,3. 
 
12.1. Subject Information 
 
12.2. Sample Size Determination 
Although there are no published data on ORR among patients with progressive disease on both 
abiraterone acetate and enzalutamide, several small studies have explored the objective response 
rates of abiraterone acetate following enzalutamide and vice versa in the post-docetaxel setting: 


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with ORRs ranging from 3-8%.5,6 Therefore, if we assume a historical-control ORR (H0) of 5% 
and an alternative hypothesis of a 25% ORR (H1), a sample size of 23 patients gives 86% power 
to detect a difference in ORR of the hypothesized magnitudes with a type-1 error of 3% based on 
an exact binomial test. We will therefore plan to enroll up to 25 patients to account for 10% 
dropout. 
 
 
12.3. Efficacy Analyses 
The primary objective will be to determine the ORR, which will be calculated as the percentage 
of patients, with 95% confidence intervals, achieving a complete response (CR) or partial 
response (PR) across the entire study population at any time. On the basis of an exact binomial 
test, 4 responses are needed to reject the null hypothesized 5% historical control ORR in favor of 
the alternative at a significance level of p=0.026. If a patient drops out of the study prior to first 
on-study radiographic assessment, they will be considered a non-responder for the purpose of the 
primary analysis; however, an additional subject will be accrued to account for early dropouts. 
We will also present ORR, with 95% confidence intervals, for the patients receiving erdafitinib 
in combination with abiraterone acetate or enzalutamide separately. Secondary objectives will 
include determining: radiographic progression free survival (PFS) in patients using RECIST 1.1 
criteria for soft tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for 
bone metastases; time to response using RECIST 1.1 criteria; overall survival (OS) defined as the 
time interval from C1D1 to the date of death; PSA response, defined as >50% reduction in PSA 
compared with baseline at any point during treatment; and the incidence and severity of    
adverse events according to National Cancer Institute-Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.02,3. Survival endpoints (e.g. PFS, OS) will be presented 
with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be 
reported as percentages with 95% CI. We will characterize AEs by type and grade. Safety will be 
summarized as the severity and frequency of a given AE. 
 
 
12.4. Correlative Research Analyses 
Exploratory correlative work will be conducted with the goal to determine if there are 
biomarkers predictive of response/resistance to erdafitinib in combination with a next-generation 
AR-signaling inhibitor. Studies to be conducted include the following. Protein expression studies 
at baseline and at the time of progression, including IHC for AR, PSA, phospho-FRS2 and 
phosphor-FGFR. Transcript profiling studies (RNA-seq) on metastatic biopsies and blood to 
assess activation of the core AR-, MAPK- and FGF/FGFR-signaling programs, and to identify 
unknown pathways involved in mediating response/resistance to treatment. Next-generation 
sequencing to assess for FGFR mutations. Baseline protein and transcript expression, as well as 
changes in these parameters with treatment, will be correlated with the primary and secondary 
endpoints using chi-square tests and logistic regression, or (for PFS and OS) using proportional 
hazards models, Kaplan-Meier methods and log-rank tests. 


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REFERENCES 
 
1. 
Bluemn EG, Coleman I, Lucas JM, et al. Androgen Receptor Pathway-Independent Prostate Cancer is 
Sustained Through FGF Signaling. Cancer cell. 2017 [In press]. 
2. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). European journal of cancer (Oxford, England : 1990). 2009;45(2):228-247. 
3. 
Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-Resistant Prostate 
Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 
2016;34(12):1402-1418. 
4. 
Labrecque MP, Coleman IM, Brown LG, et al. Molecular profiling stratifies diverse phenotypes of 
treatment-refractory metastatic castration-resistant prostate cancer. The Journal of clinical investigation. 
2019;130:4492-4505. 
5. 
Su W, Han HH, Wang Y, et al. The Polycomb Repressor Complex 1 Drives Double-Negative Prostate Cancer 
Metastasis by Coordinating Stemness and Immune Suppression. Cancer Cell. 2019;36(2):139-155 e110. 
6. 
Loriot Y, Bianchini D, Ileana E, et al. Antitumour activity of abiraterone acetate against metastatic 
castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Annals of 
oncology : official journal of the European Society for Medical Oncology / ESMO. 2013;24(7):1807-1812. 
7. 
Schrader AJ, Boegemann M, Ohlmann CH, et al. Enzalutamide in castration-resistant prostate cancer 
patients progressing after docetaxel and abiraterone. Eur Urol. 2014;65(1):30-36. 
8. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA: a cancer journal for clinicians. 2020;70(1):7-30. 
9. 
Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in metastatic prostate cancer before 
chemotherapy. N Engl J Med. 2014;371(5):424-433. 
10. 
de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. 
N Engl J Med. 2011;364(21):1995-2005. 
11. 
de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic 
castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. 
Lancet. 2010;376(9747):1147-1154. 
12. 
Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate 
cancer. N Engl J Med. 2010;363(5):411-422. 
13. 
Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. 
N Engl J Med. 2013;369(3):213-223. 
14. 
Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and 
prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513-1520. 
15. 
Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous 
chemotherapy. The New England journal of medicine. 2013;368(2):138-148. 
16. 
Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after 
chemotherapy. The New England journal of medicine. 2012;367(13):1187-1197. 
17. 
Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for 
advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512. 
18. 
Graham L, Schweizer MT. Targeting persistent androgen receptor signaling in castration-resistant prostate 
cancer. Medical oncology (Northwood, London, England). 2016;33(5):44. 
19. 
Chan JM, Zaidi S, Love JR, et al. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory 
signaling. Science (New York, NY). 2022:eabn0478. 
20. 
Beltran H, Hruszkewycz A, Scher HI, et al. The Role of Lineage Plasticity in Prostate Cancer Therapy 
Resistance. Clinical cancer research : an official journal of the American Association for Cancer Research. 
2019;25(23):6916-6924. 
21. 
Ku SY, Rosario S, Wang Y, et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, 
metastasis, and antiandrogen resistance. Science (New York, NY). 2017;355(6320):78-83. 
22. 
Brady L, Kriner M, Coleman I, et al. Inter- and intra-tumor heterogeneity of metastatic prostate cancer 


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PI: Michael T. Schweizer 
Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
determined by digital spatial gene expression profiling. Nature communications. 2021;12(1):1426. 
23. 
Schweizer MT, Antonarakis ES. Abiraterone and other novel androgen-directed strategies for the 
treatment of prostate cancer: a new era of hormonal therapies is born. Ther Adv Urol. 2012;4(4):167-178. 
24. 
Scher HI, Beer TM, Higano CS, et al. Antitumour activity of MDV3100 in castration-resistant prostate 
cancer: a phase 1-2 study. Lancet. 2010;375(9724):1437-1446. 
25. 
Haidar S, Ehmer PB, Barassin S, Batzl-Hartmann C, Hartmann RW. Effects of novel 17alpha-
hydroxylase/C17, 20-lyase (P450 17, CYP 17) inhibitors on androgen biosynthesis in vitro and in vivo. J 
Steroid Biochem Mol Biol. 2003;84(5):555-562. 
26. 
Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor 
therapeutically. J Clin Oncol. 2011;29(27):3651-3658. 
27. 
Vasaitis TS, Bruno RD, Njar VC. CYP17 inhibitors for prostate cancer therapy. J Steroid Biochem Mol Biol. 
2011;125(1-2):23-31. 
28. 
Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, 
confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 
2008;26(28):4563-4571. 
29. 
O'Donnell A, Judson I, Dowsett M, et al. Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase 
inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. British journal of cancer. 
2004;90(12):2317-2325. 
30. 
Bryce A, Ryan CJ. Development and clinical utility of abiraterone acetate as an androgen synthesis 
inhibitor. Clin Pharmacol Ther. 2012;91(1):101-108. 
31. 
Attard G, Reid AH, Auchus RJ, et al. Clinical and biochemical consequences of CYP17A1 inhibition with 
abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate 
cancer. J Clin Endocrinol Metab. 2012;97(2):507-516. 
32. 
Ryan CJ, Smith MR, Fong L, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate 
demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior 
ketoconazole therapy. J Clin Oncol. 2010;28(9):1481-1488. 
33. 
Danila DC, Morris MJ, de Bono JS, et al. Phase II multicenter study of abiraterone acetate plus prednisone 
therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol. 
2010;28(9):1496-1501. 
34. 
Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous 
chemotherapy. N Engl J Med. 2013;368(2):138-148. 
35. 
Taplin ME, Montgomery B, Logothetis CJ, et al. Intense androgen-deprivation therapy with abiraterone 
acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized 
phase II neoadjuvant study. Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. 2014;32(33):3705-3715. 
36. 
Beltran H, Tomlins S, Aparicio A, et al. Aggressive variants of castration-resistant prostate cancer. Clinical 
cancer research : an official journal of the American Association for Cancer Research. 2014;20(11):2846-
2850. 
37. 
Nadal R, Schweizer M, Kryvenko ON, Epstein JI, Eisenberger MA. Small cell carcinoma of the prostate. 
Nature reviews Urology. 2014;11(4):213-219. 
38. 
Aparicio AM, Harzstark AL, Corn PG, et al. Platinum-based chemotherapy for variant castrate-resistant 
prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer 
Research. 2013;19(13):3621-3630. 
39. 
Labrecque MP, Coleman IM, Brown LG, et al. Molecular profiling stratifies diverse phenotypes of 
treatment-refractory metastatic castration-resistant prostate cancer. The Journal of clinical investigation. 
2019;130. 
40. 
Pritchard CC, Salipante SJ, Koehler K, et al. Validation and implementation of targeted capture and 
sequencing for the detection of actionable mutation, copy number variation, and gene rearrangement in 
clinical cancer specimens. The Journal of molecular diagnostics : JMD. 2014;16(1):56-67. 


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Protocol Version: 6.0 
Version Date: 17 September 2020 
 
 
41. 
Delpuech O, Rooney C, Mooney L, et al. Identification of Pharmacodynamic Transcript Biomarkers in 
Response to FGFR Inhibition by AZD4547. Molecular cancer therapeutics. 2016;15(11):2802-2813. 
42. 
Veldman-Jones MH, Brant R, Rooney C, et al. Evaluating Robustness and Sensitivity of the NanoString 
Technologies nCounter Platform to Enable Multiplexed Gene Expression Analysis of Clinical Samples. 
Cancer research. 2015;75(13):2587-2593. 
 
 
 


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Appendix 1: ECOG Performance Status 
 
Grade 
Description 
0 
Normal  activity.  Fully  active,  able  to  carry  on  all  pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time. Ambulatory and capable of all self-care, but 
unable to carry out any work activities. Up and about more than 50% 
of waking hours. 
3 
In bed >50% of the time. Capable of only limited self-care, confined 
to bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. 
Totally confined to bed or chair. 
5 
Dead. 
* As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., 
McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology 
Group. Am J Clin Oncol 5:649-655, 1982. The Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 


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Appendix 2: Common Terminology Criteria for Adverse Events V5.0 
(CTCAE) 
 
 
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0 will be utilized for adverse event reporting. 
 
 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R 
eference_5x7.pdf 


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Appendix 3: Pill Diary Templates 
 
 


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ICF_001.pdf: 
 
 
Official Title: 
Erdafitinib plus Abiraterone Acetate or Enzalutamide in 
Double Negative Prostate Cancer 
NCT Number: 
NCT03999515 
Document Type:  
Informed Consent Form 
Date of the 
Document: 
08/20/2020 
 
 


 
057IRBform_ModelConsentClin / Version 13.00 / 01-21-2019  
Consent Version Date: 07/15/2020  
Page 1 of 20  
 
Fred Hutchinson Cancer Research Center 
Seattle Cancer Care Alliance 
University of Washington 
Consent to take part in a research study: 
Erdafitinib plus Abiraterone Acetate or Enzalutamide 
in Double Negative Prostate Cancer 
Principal Investigator: Michael T. Schweizer, MD. University of Washington; Seattle 
Cancer Care Alliance; Fred Hutchinson Cancer Research Center 
206-606-6252 
 
Drug and Funding Support: Janssen Research & Development 
Emergency number (24 hours): 206-598-6190 
Request the on-call Oncology Fellow 
Important things to know about this study. 
You are invited to participate in a research study. The purpose of this research is to 
determine if erdafitinib in combination with either enzalutamide or abiraterone 
acetate plus prednisone is effective in men with metastatic prostate cancer that has 
progressed on standard hormonal therapy. 
People who agree to join the study will be asked to attend clinic approximately once 
every 3 weeks. You will receive erdafitinib in combination with either enzalutamide or 
abiraterone acetate plus prednisone, and treatment will continue for up to two years 
as long as there is no evidence of cancer growth or serious side effects. Blood will be 
collected at least every 3 weeks to monitor the effects of the study drugs. If felt to be 
safe by the treating physician, a metastatic biopsy will be performed after stopping 
treatment. 
We do not know if erdafitinib in combination with either enzalutamide or abiraterone 
acetate plus prednisone would help treat prostate cancer, and it could even make 
your condition/disease worse. Erdafitinib in combination with either enzalutamide or 
abiraterone acetate plus prednisone could cause side effects such as blood 
electrolyte abnormalities, diarrhea, dry mouth, mouth sores, decreased appetite, 
fatigue and abnormal liver function, as described below in this form.  
You do not have to join this study. You can choose to receive standard methods to 
treat prostate cancer instead of participating in this study. We will give you details 
about the purposes, procedures, risks and possible benefits related to this study. We 
will explain other choices that you have. We will also give you any other information 
that you need in order to make an informed decision about joining this study.  
IRO received 07/31/20
 
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Following is a more complete description of this study. Please read this description 
carefully. You can ask any questions you want to help you decide whether to join the 
study. If you join this study, we will give you a signed copy of this form to keep for 
future reference.  
We invite you to join this research study. 
We invite you to join this research study because you have metastatic prostate 
cancer that has previously progressed on abiraterone acetate and/or enzalutamide. 
Up to 25 people will join this study. 
Research is not the same as treatment or medical care. The purpose of a research 
study is to answer scientific questions.  
You do not have to be in the study. You are free to say “yes” or “no”, or to drop out 
after joining. If you say “no,” you would have no penalty or loss of benefits. Whatever 
you decide, your regular medical care would not change.  
Why are we doing this study? 
We are doing this study to examine the clinical effects of erdafitinib in combination 
with either enzalutamide or abiraterone acetate plus prednisone in men with 
metastatic prostate cancer that has previously progressed on standard hormonal 
therapies. We want to know if these drugs will result in prostate cancer tumors 
shrinking on scans. 
 
Abiraterone acetate plus prednisone and enzalutamide has an anti-prostate cancer 
effect and are currently approved to be used to treat metastatic prostate cancer. 
Erdafitinib is not approved for the treatment of any cancer and is currently an 
investigational drug. We think that combining erdafitinib with enzalutamide or 
abiraterone acetate plus prednisone will result in an even greater anti-prostate 
cancer effect than any one drug alone.  
In this study, we want to learn what effects, good or bad, the study drugs (erdafitinib 
in combination with either enzalutamide or abiraterone acetate plus prednisone) 
have on people with metastatic prostate cancer. If you join this study, we would give 
you erdafitinib in combination with either enzalutamide or abiraterone acetate plus 
prednisone and watch carefully for any side effects. 
What research tests, procedures, and treatments are done in this study? 
 
Study Procedures 
 
Screening Visit 
If you agree to take part in the study, your study doctor will have up to 30 days to 
complete screening tests to see if you qualify for the study. Your study doctor will be 
collecting specific information regarding your previous and current treatments you 
may have had.  That information will be used, along with other information about 
your cancer and general health, to determine whether you are eligible. The following 
 
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tests will be done at the beginning of the study, during the screening period. Your 
study doctor can give you more details about these tests. 
 
• 
A complete medical history will be collected including information on your 
general health, past surgeries, if you suffer from pain or other problems, and 
if you are taking any other medications or have recently been on any other 
research studies.  
• 
A physical assessment including vital signs (blood pressure, heart rate and 
temperature), height, and weight, and assessment of your ability to perform 
activities of daily living. 
• 
An eye exam will be performed at an ophthalmologist.  
• 
Routine blood samples will be drawn (about 2-3 teaspoons) for laboratory 
tests that measure your blood PSA level, testosterone level, chemistries 
(including kidney and liver function), blood counts (including white blood cells, 
hemoglobin and platelets) and the ability of your blood to form clots. 
• 
An electrocardiogram (EKG) will be performed. 
• 
You will undergo a CT and bone scan if not recently performed. 
• 
A biopsy is recommended prior to enrolling to ensure that you do not have 
‘small cell’ prostate cancer – a type of prostate cancer best treated with 
chemotherapy. This biopsy will be reviewed at the time of screening.[HC1]  
 
Your study doctor will review the test results and tell you whether or not you qualify 
to be in the study and that it is reasonably safe for you to join. These tests are also 
used to make sure things do not change too much while you are in the study.  
 
Treatment Visits (approximately every 21 days) 
If you are enrolled to the study, you will continue to take either enzalutamide or 
abiraterone acetate plus prednisone. Erdafitinib will be added to your treatment 
regimen. A 3-week supply of erdafitinib will be provided at the beginning of the 
Treatment Phase of the study and you will be given a new supply of erdafitinib at 
follow up visits every 3-weeks. You will be given a diary to record your study drug 
dosing. Study staff will instruct you on how to fill out your diary.  
 
You will be evaluated for side effects and asked about all medications you are taking 
throughout the study.  Below are the tests and procedures that will be done during 
the Treatment Phase of the study. The study doctor may perform more tests and 
procedures if they feel it is necessary to monitor your safety and evaluate your 
cancer. 
 
• 
At these visits your study doctor/nurse will ask you questions to assess your 
current state of health, to determine if there has been a change in your health 
or if there have been any unexpected events since your last visit. 
• 
Review of medications you are currently taking. 
• 
You will be provided with erdafitinib as well as a diary to keep track of when 
you take your study drugs.  
• 
A physical assessment including vital signs (blood pressure, heart rate and 
temperature) and weight, and assessment of your ability to perform activities 
of daily living. This will be completed by either your doctor or a research 
nurse. 
• 
Routine blood samples will be drawn (about 2-3 teaspoons) for laboratory 
tests that measure your blood chemistries (including kidney and liver 
function) and blood counts (including white blood cells, hemoglobin and 
 
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platelets) (note: an additional blood sample will also be collected 2 weeks 
after starting). 
• 
A blood sample will be drawn to measure prostate-specific antigen (PSA) 
(approximately every 9 weeks). 
• 
You will have a blood sample collected (about 2-3 tablespoon of blood for 
research purposes) (beginning of treatment and after 9 weeks only).  
• 
You will undergo a CT and bone scan every 9 weeks. 
 
End of Treatment Visit 
• 
At this visit your study doctor/nurse will ask you questions to assess your 
current state of health, to determine if there has been a change in your health 
or if there have been any unexpected events since your last visit. 
• 
Review of medications you are currently taking. 
• 
Any unused erdafitinib will be collected at this time.  
• 
A physical assessment including vital signs (blood pressure, heart rate and 
temperature), and weight, and assessment of your ability to perform activities 
of daily living. This will be completed by either your doctor or a research 
nurse. 
• 
Routine blood samples will be drawn (about 2-3 teaspoons) for laboratory 
tests that measure your blood PSA level, testosterone level, chemistries 
(including kidney and liver function) and blood counts (including white blood 
cells, hemoglobin and platelets)  
• 
You will have a blood sample collected (about 2-3 tablespoon of blood) for 
research purposes.  
• 
You will undergo a CT and bone scan if not recently performed. 
• 
If felt to be safe by your treating physician, you will undergo a research 
biopsy. 
How long would you stay in this study? 
If you join this study, you would stay in this study as long as there is no evidence of 
cancer growth or serious side effects while receiving the study drugs, or up to about 
two years of treatment administration. After that, you would have one additional 
follow-up exam in the office or clinic within 14 days of coming off the study. 
Doctors could take you out of this study at any time. This would happen if: 
• 
They think it is in your best interest not to continue in the study. 
• 
You are not able or willing to follow study procedures. 
• 
The whole study is stopped.   
If you withdraw from the study for any reason, previously collected information would 
remain in the study records and would be included in the analysis of results. This 
information could not be removed from the study records.  
What are the side effects (risks)? 
In this part of the consent form, we describe the side effects we expect from the tests 
and treatments in this study. Erdafitinib in combination with either enzalutamide or 
 
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abiraterone acetate plus prednisone could cause side effects we do not know about 
yet. We carefully watch everyone in the study for side effects.   
If you join this study, we would tell you if we discover new side effects that could 
affect you.  
This form lists side effects of individual drugs. Other side effects could occur when 
we use these drugs together. 
Side effects may be mild or very serious. Medicines could be given to help lessen 
side effects. Many side effects go away soon after you stop taking erdafitinib in 
combination with either enzalutamide or abiraterone acetate plus prednisone. In 
some cases, side effects can last a long time or never go away.  
Risks of Erdafitinib 
 
As of June 4, 2019, 562 subjects with different types of cancer have received treatment 
with erdafitinib monotherapy across 12 ongoing and completed  clinical studies. Side 
effects seen in five (5) pooled  studies, which enrolled a total of 501 subjects, are 
summarized below. 
 
Risks and side effects that could be related to erdafitinib include:  
Very Common (occurring in more than 35% of subjects) 
• 
Higher than normal levels of phosphate in the blood  
• 
Dry mouth  
• 
Swelling, redness, pain, or ulcers of the mouth  
• 
Diarrhea 
Common (occurring in 10% to 35% of subjects)  
• 
separation of the fingernail or toenail from the nail bed)  
• 
Infection of the fingernail or toenail 
• 
Weakness 
• 
Constipation 
• 
Distortion of the sense of taste 
• 
Vomiting 
• 
Nausea 
• 
Abdominal pain 
• 
Skin problems including dryness and cracking  
• 
Dry eye  
• 
Loss of hair 
• 
Low number of red blood cells which may cause tiredness or shortness of 
breath 
• 
Pain in joints 
• 
Fatigue  
• 
Back pain 
• 
Fever 
• 
Abnormal liver function tests 
• 
Urinary tract infection 
• 
Shortness of breath or trouble breathing  
 
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• 
Discomfort of the palms of the hands and soles of the feet that can range from 
a burning sensation or pain to peeling of the skin 
• 
Decreased appetite 
• 
Weight loss 
• 
Cough 
• 
Nose bleeds 
• 
Reversible fluid accumulation and swelling of the retina (internal part of the 
eye) that may or may not be associated with visual symptoms such as blurred 
or diminished vision or loss of vision 
Uncommon (occurring in 5% to less than 10% of subjects)  
• 
Itchy skin 
• 
Nail changes including brittleness, peeling, discoloration, ridging, and 
breakage 
• 
Indigestion 
• 
Difficulty or pain swallowing 
• 
Dry nose 
• 
Low sodium in the blood, which may cause weakness or confusion 
• 
Low magnesium in blood which, may cause muscle cramps, weakness, 
tremors or irregular heartbeat 
• 
High calcium in the blood, which may cause an increase in urination and thirst, 
bone pain, headaches, weakness and muscle cramps 
• 
Pain in arms or legs 
• 
Pain in muscles or bones 
• 
Insomnia (inability to sleep) 
• 
Blood in the urine 
• 
Redness, irritation, and infection of the eye 
• 
Increased tearing of the eye 
• 
Decreased blood pressure 
• 
Build-up of fluid in the body causing swelling 
• 
Headache 
• 
Increased level of a type of a-protein (alkaline phosphatase) in the blood 
• 
Increased level of a chemical waste product creatinine in the blood 
• 
Blurry vision 
 
Most side effects experienced by subjects were mild to moderate in severity and most 
of the side effects were reversible when the study drug was stopped. In rare cases 
some subjects experienced serious side effects. 
 
Not all of the possible side effects and risks related to erdafitinib are known at this 
time. Other currently unknown risks and discomforts could appear. The new side 
effects may be mild or severe and may or may not be reversible and could also result 
in death. You will be monitored very closely by your doctor and his/her team for any 
side effect that may be caused by the study drug. You will receive appropriate care if 
side effects occur. If you experience nail or skin side effects, your study doctor may 
ask to take a photograph so that your condition can be monitored and assessed.  
Please tell your study doctor if you have any of the side effects described above or 
any other ones not listed. You will be told of any new findings that may affect your 
decision to continue in this study.  
 
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It is very important that any new health problem is quickly reported to the 
investigator, regardless of whether or not you think it has to do with the study. 
Erdafitinib is cleared from the body by the liver and may interact with other drugs that 
are cleared in the liver. There are certain medications that should not be taken with 
erdafitinib. Therefore, it is important that you do not take any medication, food 
supplements, or herbal products unless it is discussed with and approved by your 
study doctor first.  
 
The activity of erdafitinib may be significantly decreased when given in combination 
with enzalutamide. In addition, other drugs may also result in decreased activity of 
erdafitinib when given in combination. You should discuss the potential for these 
drug interactions with your treating physician before signing this consent form. 
 
Reproductive Risks associated with Erdafitinib 
The effect of erdafitinib on sperm is unknown. From when you start taking the study 
drug until 3 months after your last dose, you must use a condom with spermicide 
when you have sex and must not donate sperm. In addition, your partner must use a 
recognized form of contraception as described below unless they are surgically 
sterile. This is done to prevent pregnancy. If you have had a vasectomy (confirmed 
to be successful), you do not need to use a condom for birth control. If your partner 
becomes pregnant in the time between when you start taking the study drug until 3 
months after your last dose, you must tell the study doctor immediately. The sponsor 
may ask you and your partner to allow them to collect information about her 
pregnancy and the health of the baby.  
If your partner is able to have children [and you are sexually active], your partner 
must use highly effective birth control (contraception) during the study and until 3 
months after taking the last dose of study drug. For women, birth control methods 
that can be used while their partner is on this study include hormonal prescription 
oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, 
surgical sterility, or true sexual abstinence. True sexual abstinence is also an 
acceptable method and is defined as refraining from heterosexual intercourse during 
the entire period of the study including up to 3 months after the last dose of drug is 
given. Periodic abstinence (calendar, symptothermal, post-ovulation methods) 
however is not considered acceptable. The type of birth control your partner utilizes 
must be discussed with the study doctor before you begin the study. The study 
doctor must approve the method you use before you can enter the study. 
Risks of Abiraterone Acetate 
 
At present, known side effects related to abiraterone acetate include:   
 
Frequent (occurring in 20% or more subjects)  
• 
Hypokalaemia (low blood potassium, a mineral that helps regulate heart 
rate/function, fluid balance in the body and is needed for adequate body 
function) 
• 
Hypertension (high blood pressure) 
 
Very Common (occurring in 10% to 20% of subjects)  
 
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• 
Edema peripheral (swelling of the legs as a result of the body keeping too 
much fluid) 
 
Common (occurring in 5% to 10% of subjects)   
• 
Dyspepsia (uncomfortable feeling in upper belly, indigestion)  
• 
Hematuria (presence of blood in the urine) 
• Alanine aminotransferase increased (an enzyme in the blood that 
measures the function of the liver) 
• 
Urinary tract infection 
• 
Fractures (a break in the bone) 
 
Less Common (occurring in fewer than 5% of subjects) 
• 
Hypertriglyceridemia (high levels of fats (triglycerides) in the blood)  
• 
Angina pectoris (chest pain from the heart) 
• 
Atrial fibrillation (a fast and irregular heartbeat) 
• 
Tachycardia (rapid heartbeats) 
 
Uncommon (occurring in fewer than 1% of subjects)  
• 
Adrenal insufficiency (decreased function of adrenal glands that normally help 
maintain blood pressure, balance minerals and fluid in your body) 
• 
Cardiac failure (heart failure, the heart is unable to supply enough blood flow 
to meet the body's needs.)  
• 
Arrhythmia (changes in the rhythm of the heart) 
• 
Abnormal ECG with QT prolongation (an abnormal finding on the ECG) 
• 
Bone density decreased (loss of strength of bones)  
• 
Myopathy (muscle weakness and/or muscle pain). 
 
Unknown (frequency isn’t determined since data was derived from post-marketing 
experience and there was no report from clinical studies 
• 
Failure of the liver to function (called acute liver failure) 
• 
Allergic alveolitis (swelling and irritation of the lung)  
• 
Rhabdomyolysis (breakdown of muscle tissue) 
• 
Torsades de Pointes (rapid or irregular heart rate associated with feeling faint 
or lightheaded) 
• 
Anaphylactic reaction (severe allergic reaction that may include symptoms 
such as difficulty swallowing or breathing, swollen face, lips, mouth, tongue or 
throat, or an itchy rash 
 
There is a small chance of severe allergic reaction to the drug which may be life-
threatening. 
Abiraterone acetate may cause harm to the liver. Approximately 13% of patients taking 
abiraterone acetate have had abnormal blood levels of liver enzymes. Rarely, failure 
of the liver to function may occur, which can lead to death. Interruption or 
discontinuation of the treatment with abiraterone acetate was sufficient to normalize 
the liver enzymes in majority of these cases. Your liver function will be monitored 
closely by blood tests every two weeks for the first 3 months of the study and monthly 
thereafter. If elevations in your liver function enzymes are observed, the dose of your 
study medication will be adjusted or discontinued. 
 
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Abiraterone acetate should be used with caution in patients with a history of heart 
disease. Before treatment with abiraterone acetate, high blood pressure must be 
controlled and low potassium must be corrected. Potassium is needed for proper 
function of your heart, and other essential body systems.   
It is important that you contact your study doctor right away if you cannot come to your 
regularly scheduled visit or get your blood tests. This is because some patients have 
no symptoms when their blood potassium is low. Contact your study doctor 
immediately if: 
• 
 You feel weak; have constipation, muscle pain, or cramps.  These symptoms 
may be caused by low blood potassium.   
• 
Your appetite decreases, or if you develop diarrhea. Potassium may become 
low if you are not eating well or is lost through diarrhea.  
 
Certain drugs may interact with abiraterone acetate.  You need to tell your study 
doctor of all medications and supplements (e.g., herbs, vitamins) you take. 
 
If you have diabetes, your blood sugar may drop if you take Zytiga plus 
prednisone/prednisolone with some medicines for diabetes such as pioglitazone or 
repaglinide.  Tell your healthcare provider if you monitor your blood sugar while 
taking a medicine for diabetes and notice a drop in your blood sugar.   
 
The study treatment must be taken only by you.  It must also be kept out of the reach 
of children or persons of limited capacity to understand. 
 
Abiraterone acetate or placebo is provided as 250 mg tablets.  You will take 4 tablets 
by mouth once daily on an empty stomach.  No food should be eaten for at least 2 
hours before taking the tablets and for at least one hour after taking the tablets. The 
tablets should be swallowed whole with water.  It is important to stay on this schedule.  
How abiraterone acetate enters your body can be quite different depending on when 
you eat.  This is why abiraterone acetate should not be taken with food.   
Abiraterone acetate must be stored at room temperature (between 15ºC to 30ºC, or 
59°F to 86°F) with the cap on tightly and should not be refrigerated. If you miss a dose 
of study drug, do not try to make it up. It should be omitted. 
 
Reproductive Risks associated with Abiraterone Acetate 
Abiraterone acetate should not be handled by pregnant women or women of child 
bearing potential unless protective gloves are worn. 
 
Abiraterone acetate may cause harm to the unborn child and the effect of the study 
drug on your sperm is unknown. 
 
Risks of Prednisone 
 
 
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Prednisone is given with abiraterone acetate to reduce or stop some of the side effects 
of abiraterone acetate, such as high blood pressure, low blood potassium, and swelling 
of the legs.   
You should tell the study doctor if you have ever had a reaction to prednisone. You 
may ask your doctor for printed information about prednisone and the potential side 
effects (this is called a package insert). 
Prednisone is a type of drug called a corticosteroid. Corticosteroids can weaken your 
body’s ability to fight off infection and can make infections hard to diagnose or treat. If 
you develop fever, or suspect you have an infection, you should alert your study doctor 
right away. 
Other side effects caused by corticosteroids are: 
• 
Fluid retention 
• 
Stomach bleeding 
• 
Indigestion 
• 
Seizures 
• 
Swelling of the brain 
• 
Emotional changes 
• 
Mood swings or severe depression 
• 
Eye problems such as cataracts or glaucoma 
• 
Insomnia (sleeplessness, wakefulness) 
• 
Elevated blood sugar (for diabetics, this can make your glucose level more difficult to 
       control) 
• 
Increased risk of glucocorticoid-induced bone loss (decreasing bone absorption and 
increasing excretion) 
 
Possible risks associated with long term use of corticosteroids: 
Cushing’s syndrome: Taking corticosteroids over a long period of time can cause a 
condition called Cushing’s syndrome. Symptoms of Cushing’s syndrome include: 
• 
Weight gain 
• 
Muscle weakness 
• 
A moon faced appearance 
• 
Thin, fragile skin 
• 
Brittle bones 
• 
Purplish stripe marks on the skin 
 
Adrenal insufficiency may occur due to long term use of steroid medicines taken orally. 
It can be life threatening at times of major illness and extreme physical stress. 
Symptoms of adrenal insufficiency include: 
• 
Weakness and fatigue 
• 
Low blood pressure 
• 
Nausea 
• 
Vomiting 
• 
Diarrhea 
• 
Irritability and/or restlessness 
 
Prednisone should never be stopped suddenly. If you need to stop your doctor will 
advise on how to slowly cut down the dose and stop the drug. If you were to stop taking 
prednisone suddenly you could have: 
 
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• 
Weakness and tiredness 
• 
Very low blood pressure 
• 
Very low blood sugar 
• 
Abnormal blood minerals 
 
While these reactions are usually not severe, they are potentially fatal if not treated. 
Risks of Enzalutamide 
 
At present, known side effects related to enzalutamide include:   
Likely Risks (occurring in >10% of subjects) 
• 
Enlargement of breast tissue (Gynecomastia) 
• 
Hot Flashes 
 
Less Likely Risks (occurring in 1% to 10% of subjects) 
• 
Fatigue 
• 
Diarrhea 
• 
Nausea 
• 
Rash 
 
Rare but Serious (occurring in less than <1% of subjects) 
• 
Seizures 
 
If you experience a side effect, your treating doctor may change your enzalutamide 
doses in an effort to decrease or stop any side effects. If severe side effects do 
develop, you and your doctor may decide that it is in your best interest to stop taking 
part in the study. If you choose, you always have the right to withdraw from the 
study. In addition, you will be provided with the telephone numbers for people who 
can answer any questions about the study, your rights as a study participant and for 
you to report any side effects. 
 
Reproductive Risks associated with Enzalutamide 
Enzalutamide may be harmful to a developing fetus. Men who are sexually active with 
a pregnant woman must use a condom during and for 3 months after treatment with 
enzalutamide. If their sexual partner may become pregnant, a condom and another 
form of birth control must be used during and for 3 months after treatment.  
Risks of Blood Draw 
You may feel some discomfort when the needle is placed in your vein to draw blood 
for testing. Sometimes a bruise may develop where the blood was drawn or the 
needle was placed, and occasionally infection or bleeding may develop at the 
puncture site. Light-headedness and/or fainting may occur during blood collection. 
 
Radiation Risks 
Some of the tests that you will have in this research study will expose you to 
radiation. Everyone receives a small amount of radiation every day called 
“background radiation”. This radiation is natural and comes from space, air, water, 
soil, and the food you eat. Each year you are exposed to about 3 milliSieverts (mSv) 
of this background radiation. A milliSievert is a unit of radiation dose. For 
comparison, the estimated radiation dose from each of these tests is listed below. 
 
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The risk to your health from this level of radiation exposure is too low to be 
detectable and may be nonexistent. 
• 
Abdomen CT: 8 mSv 
• 
Chest CT: 7 mSv 
• 
Pelvis CT: 6 mSv 
• 
Bone Scan: 5.3 
Non-physical risks 
• 
You might not be able to work. 
• 
Results of genetic tests might be released by accident. This risk is very low, 
because we keep personal information private. If these results became known, 
you could have problems with family members or insurance. 
• 
There may be psychological, emotional, financial, social, and legal risks that 
might result.  These risks include change in emotional state, anxiety, or 
depression associated with taking the study drugs. There may be financial risks 
related to reimbursement for study procedures.  
What are the benefits? 
There may or may not be a direct benefit to you from taking part in this study. We are 
testing erdafitinib in combination with either enzalutamide or abiraterone acetate plus 
prednisone to see its effects on people with prostate cancer.  You might get better if 
you receive these study drugs, but your condition could stay the same or even get 
worse.  
Patients may derive no benefit from the continuation of abiraterone acetate or 
enzalutamide with the addition of erdafitinib.  
We hope the information from this study will help other people with prostate cancer in 
the future. 
You have other choices besides this study. 
You do not have to join this study. You are free to say “yes” or “no”. Your regular 
medical care would not change if you decide to say “no”.  
You have other choices for treatment.  Each of these choices has risks and benefits. 
You should talk to your doctor or healthcare provider about these choices.   
Other choices include: standard treatment, another research study, no treatment or 
comfort care.  
Enrollment in this study may exclude you from other research studies.  
 
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Protecting Privacy as an Individual and the Confidentiality of Personal 
Information  
If you join this study, some people or organizations might need to look at your 
medical records and research records for quality assurance or data analysis. They 
include: 
• 
Researchers involved with this study. 
• 
University of Washington (the study site) and their agents.  
• 
Institutional Review Boards (IRB), including the Fred Hutchinson Cancer 
Research Center IRB. An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
• 
Fred Hutchinson Cancer Research Center, University of Washington, and 
Seattle Cancer Care Alliance. 
• 
Office for Human Research Protections, Food and Drug Administration, 
and other regulatory agencies as required. 
• 
Janssen Scientific Affairs, LLC 
We will do our best to keep personal information confidential. But we cannot 
guarantee total confidentiality.  Personal information may be given out if required by 
law.  For example, workplace safety rules may require health workers to contact you 
about lab tests. Or a court may order study information to be disclosed. Such cases 
are rare. 
We will not use personal information in any reports about this study, such as journal 
articles or presentations at scientific meetings. 
 
If you join this study, information about your participation would be made part of your 
permanent medical record. This information would include a copy of this consent form. If 
an insurance company or employer or anyone else were authorized to see your medical 
record, they would see a copy of this consent form.  
Would we pay you if you join this study? 
There is no payment for being in this study. 
It is possible that this research could lead to discoveries that could be licensed or 
patented. You will not benefit financially from products developed through this study. 
Would you have extra costs if you join this study?  
If you join this study, you would have some extra costs. Your insurance company 
might pay these costs, but some insurance policies do not cover these costs. We 
could help find out whether your insurance company would cover these costs. 
 
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The extra costs are: 
• 
Cost of tests that are given more often than usual. 
• 
Cost of enzalutamide or abiraterone acetate plus prednisone. 
• 
Cost of standard doctor visits and lab tests. 
• 
Cost of any other medical care needed because of this study. 
If you join this study, you or your insurance company would have to pay for the costs 
of standard treatment in this study. 
You would not be billed for: 
• 
Erdafitinib 
• 
Blood collected solely for research purposes 
• 
Biopsy done solely for research purposes 
 
You or your insurance company will be charged for portions of your care during this 
research study that are considered standard care. You may be responsible for co-
payments and deductibles that are typical for your insurance coverage. 
Check with your insurer before you join this study. 
The National Cancer Institute provides an online resource to help people 
participating in cancer clinical trials understand which services their insurance 
company is required by law to pay. This can be found at the website below or can be 
provided by the study team: 
www.cancer.gov or 1-800-4-CANCER (1-800-422-6237) 
What if you get sick or hurt after you join this study? 
 
 
For a life-threatening problem, call 911 right away or seek help immediately.  Contact 
your study doctor when the medical emergency is over or as soon as you can.    
 
For all other medical problems or illness related to this research, immediately contact 
your study doctor, Dr. Michael T. Schweizer, at (206) 606-6252 (business hours) or 
(206) 598-6190 (after hours).  
 
If you have a physical injury as a direct result of being in this study, we will treat you 
or refer you for treatment. The costs of the treatment may be billed to you or your 
health insurance just like other medical costs, or it may be covered by the UW’s 
discretionary Human Subjects Assistance Program (HSAP), depending on a number 
of factors.  The researcher may request HSAP coverage by following established 
procedures. If you wish to request HSAP coverage yourself, contact the researcher 
or the UW Human Subjects Division at hsdinfo@uw.edu or 206-543-0098. You may 
also call collect to the UW Human Subjects Division at 206-221-5940 if you do not 
otherwise have access to a telephone. Ask the researcher if you would like 
information about the limits and conditions of the HSAP. The UW does not normally 
provide any other form of compensation for injury. However, the law may allow you 
 
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to seek payment for injury-related expenses if they are caused by malpractice or the 
fault of the researchers. You do not waive any right to seek payment by signing this 
consent form.  
You or your insurer will be billed for treatment of problems or complications that 
result from your condition or from standard clinical care. 
 
You would not lose any legal right to seek payment for treatment if you sign this 
form. 
 
What will my information and/or tissue samples be used for? 
Your information and tissue samples (such as blood and tumor cells) will be used for 
the purposes of this study. 
Your tissue samples might help researchers develop new products. This research 
could be done by for-profit companies. There is no plan to share with you any 
revenue generated from products developed using your tissue samples. 
During this study, if the researchers learn new information that may be important to 
your general health or to your disease or condition, they will share that information 
with you. This would include any genetic changes (mutations) detected in your 
cancer, as detected by standard tests. 
In addition, be aware that by agreeing to participate in this study, your information or 
tissue samples could be used for future research studies or sent to other 
investigators for future research studies without additional consent from you. These 
future research studies will be reviewed by an oversight group known as an 
institutional review board if required by law. The information that identifies you will 
first be removed from your information or tissue samples. If you do not want your 
information or tissue samples to be used for future research studies without your 
consent, you should not participate in this study. 
Your tissue contains DNA. DNA makes up the genes that serve as the "instruction 
book" for the cells in our bodies. By studying genes, researchers can learn more 
about diseases such as cancer. There are many different types of genetic tests. The 
testing on your tissue samples might include genetic testing called whole genome 
sequencing. Whole genome sequencing looks at all the known genes in your cells. 
This type of testing can provide useful information to researchers. It can also present 
risks if the test results became known to others, for example you could have 
problems with family members or insurance companies. There is also a risk that 
these test results could be combined with other genetic information to identify you. 
Future genetic research 
Several genetic databases are available to help researchers understand different 
diseases. These databases contain DNA code and medical information from 
participants who have various diseases.  
As part of this study, we might release DNA code and information about your medical 
condition into a genetic database in order to help future research. The genetic 
 
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database would not contain names, addresses, or other information that could be 
used to identify you.  
The DNA code in a genetic database cannot be used by itself to identify any specific 
person. A researcher who already has DNA code about you could use information 
from a genetic database to learn more about you. Once we release information to a 
genetic database, we no longer have any control over the use of this information.  
How is my genetic information protected? 
A federal law called the Genetic Information Nondiscrimination Act (GINA) helps 
protect genetic information about people who join research studies.  
GINA restricts access to genetic information so that it cannot be used for health 
insurance coverage decisions. GINA prevent health insurance companies or group 
health plans from  
• Asking for genetic information obtained in research studies, or
• Using genetic information when making decisions regarding your eligibility or
premiums
GINA does not help or protect against genetic discrimination by companies that sell 
life, disability or long-term care insurance.  
How long will my samples be stored? 
Your samples will be stored for up to five years following the completion of this study. 
Samples will be stored at University of Washington and/or Fred Hutchinson Cancer 
Research Center for research purposes only. These samples may also be sent to 
our research partners participating in this study. University of Washington and our 
research partners work to understand and cure diseases. The biospecimens and/or 
data you provide are important to this effort. Researchers will not report their results 
to you or your doctor. Your specimens will not be used for reasons unrelated to this 
research study. All specimens will be kept in locked research laboratories at 
University of Washington and/or Fred Hutchinson Cancer Research Center. The use 
of these specimens will be supervised by the primary investigators at University of 
Washington (Michael T. Schweizer, MD) and their designees. These samples will not 
contain your name or other identifiable information. Analyses will be conducted at the 
University of Washington and/or Fred Hutchinson Cancer Research Center. 
Your rights 
•
You do not have to join this study. You are free to say “yes” or “no”.
•
If you get sick or hurt in this study, you do not lose any of your legal rights to seek
payment by signing this form.
•
During the study, we might learn new information that you need to know. For
example, some information may affect your health or well-being. Other information
might make you change your mind about being in this study. If we learn these
kinds of information, we would tell you.
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Consent Release Date: 08/20/2020
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• 
If you join this study, you would not have to stay in it. You could stop at any time 
(even before you start). Your regular medical care would not change. You would 
have no penalty for stopping, but it would be better not to join the study if you 
think that you would change your mind later.  
• 
If you decide to drop out, we would want you to tell the study doctor. The doctor 
could tell you about the effects of stopping erdafitinib in combination with either 
enzalutamide or abiraterone acetate plus prednisone. You and the doctor could 
talk about the follow-up care and testing that would help the most.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. 
At most, the Web site will include a summary of the results. You can search this Web 
site at any time.  
Your responsibilities 
If you join this study, you would have some responsibilities.  
• 
Follow the schedule of study visits and procedures. 
• 
Takes study medications as directed.  
• 
Prevent pregnancy. 
• 
Tell us about side effects.    
 
RG1005038
IRB Approved 
Consent Release Date: 08/20/2020
Printed on 9/10/2020


 
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For more information 
If you have questions or concerns about this study, you could talk to your doctor 
anytime. Other people you could talk to are listed below. 
 
If you 
have questions about: 
 
Call: 
This study (including 
complaints and requests for 
information) 
 
(206) 606-6252 (Dr. Michael T. Schweizer) 
(206) 598-6190 (Oncology Fellow on-call 24 Hour) 
If you get sick or hurt in this 
study 
 
(206) 606-6252 (Dr. Michael T. Schweizer) 
Your rights as a research 
participant 
 
206-667-5900 or email irodirector@fredhutch.org 
(Director of Institutional Review Office, Fred 
Hutchinson Cancer Research Center) 
206-543-0098 (Human Subjects Division, 
University of Washington) 
Your bills and health 
insurance coverage 
 
206-598-8260 (UWMC Patient Financial Services)  
206-606-1091 (SCCA Patient Financial Clearance) 
Emergency number (24 hours): (206) 598-6190 
Request the on-call Oncology Fellow 
 
 
 
RG1005038
IRB Approved 
Consent Release Date: 08/20/2020
Printed on 9/10/2020


 
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Signatures 
Please sign below if you:  
• 
have read this form (or had it read to you); 
• 
had the opportunity to ask any questions you have; 
• 
had the opportunity to discuss the research with the person obtaining 
consent; and  
• 
agree to participate in this study. 
 
Participant: 
 
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
 
I agree to provide pre-treatment and post-treatment biospecimens including blood 
and tumor tissue. 
 
Participant: 
 
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
 
 
If you served as an interpreter or witness during the consent process, sign below to 
indicate you attest to the accuracy of the presentation to the participant and the 
apparent understanding of the research by the participant. 
 
Impartial Witness or Interpreter: 
 
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
 
Researcher’s statement 
I have discussed the research study, including procedures and risks, with the person 
signing above. A copy of the signed consent form will be given to the participant. 
 
Person obtaining consent signature: 
 
 
 
 
 
Printed Name 
 
Signature 
 
Date 
 
 
FHCRC IRB Approval  
08 20 2020 
Document Released Date
 
RG1005038
IRB Approved 
Consent Release Date: 08/20/2020
Printed on 9/10/2020


 
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Protocol: 10288 
Current version date: 07/15/2020 
Previous version date: 08/12/2019 
Copies to: Researcher’s file 
 Subject 
 Subject’s medical record (if applicable) 
 
RG1005038
IRB Approved 
Consent Release Date: 08/20/2020
Printed on 9/10/2020