MATCH Treatment Subprotocol K2: Phase 2 Study of Erdafitinib (JNJ-42756493) in Patients With Tumors With FGFR Mutations or Fusions
Phase: PHASE2
Conditions: Malignant Solid Neoplasm
Sponsor: National Cancer Institute (NCI)

i
28 State Street, Suite 1100, Boston, MA 02109
p: 857.504.2900
f: 617. 589.0914
ecog-acrin.org
August 19, 2020
Martha Kruhm, MS RAC
Head, Protocol and Information Office
Quality Assurance Section
CTEP, DCT, NCI
6130 Executive Blvd, EPN Room 7000
Bethesda, MD   20892
Dear Ms. Kruhm:
Enclosed is Addendum #25 to EAY131-K2, Phase 2 Study of JNJ-42756493 (erdafitinib) in 
Patients with Tumors with FGFR Mutations or Fusions.
This addendum is in response to Dr. Tali Johnson’s Amendment Request for updates to specific 
protocol language for Crizotinib dated June 5, 2020.
Please replace your current copy of the protocol and Informed Consent document with these 
updated versions. We recommend that each institution maintain a file containing the original 
protocol, Informed Consent, and all subsequent revisions/versions.
IRB Review Requirements:
This addendum has been reviewed and approved by the Central IRB, which is the sole 
IRB of record for this study. Local IRB review and approval is unnecessary.
Implementation of this addendum must occur on the activation date. Sites are not 
permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 
after the activation date of this addendum.
Re: Review of Amendment #36 of Protocol #EAY131-K2: “MATCH Treatment Subprotocol K2: 
Phase 2 Study of Erdafitinib (JNJ-42756493) in Patients with Tumors with FGFR Mutations or 
Fusions”. The following are ECOG-ACRIN’s responses to the CTEP review comments dated 
06/03/2020. Please note that the Principal Investigator’s comments appear in bold below.
I. Company Comments – Requiring a Response: 
#
Section
Comments
1.
5
As per CTEP’s CRADA with J&J for erdafitinib, please add a subsection to 
Section 13 with the following information:
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 

ii
#
Section
Comments
subject. Lot and batch numbers are of high significance and need to be 
provided upon request.
PQC should be reported to CTEP.
Examples of PQC include but not limited to:
x Functional Problem: e.g., altered delivery rate in a controlled release 
product
x Physical Defect: e.g. abnormal odor, broken or crushed 
tablets/capsules
x Potential Dosing Device Malfunction: e.g., autoinjector button not 
working, needle detaching from syringe
x Suspected Contamination
x Suspected Counterfeit
PI Response: Thank you for this recommendation. This arm is closed 
with one patient remaining on treatment and no plans at this time to 
re-open to accrual. Given the status of this arm, the study team does 
not suspect the addition of PQC will considerably impact the lone 
participant on treatment, thus, have opted not to add this language 
as a sub section. 
2.
3
As per CTEP’s CRADA with J&J for erdafitinib, please add a subsection to 
Section 13 with the following information:
Special Reporting Situations
In accordance with the protocol the following special situations, which are 
safety events of interest for a J&J medicinal product that require 
expediting reporting and/or safety evaluation with or without an SAE 
include:
x Drug exposure during pregnancy (maternal)
x Suspected abuse/misuse of a J&J medicinal product
The following Special Situations should be reported if associated with an 
SAE or as defined within the protocol 
x Overdose of a J&J medicinal product
x Exposure to a J&J medicinal product from breastfeeding 
x Inadvertent or accidental exposure to a J&J medicinal product
x Any failure of expected pharmacological action (i.e., lack of effect) of a 
J&J medicinal product 
x Medication error 
x Suspected transmission of any infectious agent via administration of a 
medicinal product 
These safety events may not meet the definition of an adverse event; 
however, from a COLLABORATOR perspective, they are treated in the 
same manner as adverse events. Special Situations should be recorded 
on the appropriate CRF.
PI Response: Thank you for this recommendation. This arm is closed 
with one patient remaining on treatment and no plans at this time to 

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#
Section
Comments
re-open to accrual. Given the status of this arm, the study team does 
not suspect the addition of this language for ‘Special Reporting 
Situations’ will considerably impact the lone participant on 
treatment, thus, have opted not to add this language as a sub 
section.
3.
3
As per CTEP’s CRADA with J&J for erdafitinib, please add in the 
appropriate subsection of Section 13 the following information:
The following Adverse Events of Special Interest, whether or not 
resulting in hospitalization, should be reported via CTEP-AERS. 
x 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.
PI Response: Thank you for this recommendation. This arm is closed 
with one patient remaining on treatment and no plans at this time to 
re-open to accrual. Given the status of this arm, the study team does 
not suspect the addition of this language regarding ‘Adverse Events 
of Special Interest’ will considerably impact the lone participant on 
treatment, thus, have opted not to add this language as a sub 
section. 
Re: The following are ECOG-ACRIN’s responses to the CTEP’s Review of Amendment # 24 of 
Protocol # EAY131-K2, entitled, “Phase 2 Study of JNJ-42756493 (erdafitinib) in Patients with 
Tumors with FGFR Mutations or Fusions.” dated December 16, 2019, from the disapproval of 
Addendum #24 first submission to CTEP. Please note that the Principal Investigator’s 
comments appear in bold below:
II. Company Comments – Requiring a Response: 
#
Section
Comments
4.
1.2.2
In EAY131-K2 (p. 10) please update the phase 2 experience (BLC2001 has efficacy 
data) and other ongoing studies as there are additional studies OR note in the 
protocol section to refer to the current IB for the latest information.
PI Response: Thank you.  We’ve noted in the protocol section for sites to refer 
to the current IB for the latest updates.
5.
3.2.1
In EAY131-K2 (p. 16), pregnancy is an expedited reporting requirement of female 
partners of male subjects as well as female subjects.  The effect of erdafitinib on 
sperm is unknown. This would be consistent with what is currently in the ICF.
PI Response: It is EA’s policy to only collect pregnancy data on registered 
female patients.  EA does not collect medical information on non- registered 
female partners of male patients or on pregnancy outcomes on non-registered 
patients
III. Company Comments – Recommendations (no response required): 

iv
#
Section
Comments
6.
3.1
Protocol EAY131-K2 (p. 15), erdafitinib may be administered with or without food.  
To be consistent with previous dosing, it would be acceptable to keep as is, but it is 
not required to take 1 hr before eating or 2 hrs after a meal.  If this is changed to be 
with or without food, Appendix 1, #5 should be deleted.
PI Response: This has been revised.
IV.
Additional Changes by Principal Investigator:
The following revisions to EAY131-K2 protocol have been made in this addendum:
Section
Change
1.
Cover Page
Updated Version Date and addendum number.  
2.
Cover Page
Updated study title. 
3.
Contacts Page
Updated Dr. Ingrid Mayer’s email address. 
4.
Global
Administrative edits throughout. 
5.
3.2.1
Revised language referencing “subject” in the second box to “female 
patient”.
6.
3.4
Changed language from “medical monitor” to “study chair” throughout the 
section for clarity.
7.
5
Revised “Drug Formulation and Procurement” pharmacy information 
throughout.
8.
Appendix II
Removed duplicate fusion variant from aMOI list. 
9.
Appendix II
Added novel aMOIs to aMOI list. 
10.
Appendix III
Updated patient handout information and wallet card.
The following revisions to EAY131-K2 Informed Consent Document have been made in this 
addendum:
Section
Change
Global 
Administrative edits throughout.
1.
Page 1
Updated Version Date.
If you have any questions regarding this addendum, please contact aagu@ecog-acrin.org or 
857-504-2900.
We request review and approval of this addendum to EAY131-K2 so ECOG-ACRIN may 
activate it promptly.  
Thank you.
Sincerely,
Pamela Cogliano
Senior Director of Protocol Development

EAY131-K2
1
Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K2: Phase 2 Study of 
Erdafitinib (JNJ-42756493) in Patients with Tumors with 
FGFR Mutations or Fusions
JNJ-42756493 (ERDAFITINIB) TREATMENT 
SUBPROTOCOL CHAIR:
Alain Mita, MD
JNJ-42756493 (ERDAFITINIB) TREATMENT 
SUBPROTOCOL CO-CHAIR:
Ingrid Mayer, MD
JNJ-42756493 (ERDAFITINIB) TRANSLATIONAL 
CHAIR:
Heather Cheng, MD, PhD
Version Date: August 19, 2020
NOTE: This subprotocol (EAY131-K2) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131).
SUBPROTOCOL ACTIVATION DATE
Incorporated in Addendum #13
Addendum #16
Addendum #19
Addendum #25
Agent
IND#
NSC#
Supply
JNJ-42756493 (erdafitinib)
IND Sponsor: DCTD, NCI IND#: 
781558
NCI Supplied

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Version Date: August 19, 2020
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Table of Contents
Molecular Analysis for Therapy Choice (MATCH) ...................................................... i 
MATCH Treatment Subprotocol K2: Phase 2 Study of Erdafitinib (JNJ-42756493) in 
Patients with Tumors with FGFR Mutations or Fusions ..................................... 1 
Table of Contents ...................................................................................................... 2 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 JNJ-42756493 (erdafitinib) ........................................................................ 5 
1.2 Supporting Preliminary Data ..................................................................... 8 
1.3 Rationale for 8 mg starting and 9 mg up-titration dose: .......................... 9 
2. Selection of Patients ......................................................................................... 11 
2.1 Registration to Treatment ....................................................................... 11 
3. JNJ-42756493 (erdafitinib) Treatment Plan ...................................................... 14 
3.1 Administration Schedule ......................................................................... 14 
3.2 Adverse Event Reporting Requirements ................................................. 15 
3.3 Comprehensive Adverse Events and Potential Risks List (CAEPR) for JNJ-
42756493 (Erdafitinib, NSC 781558) ....................................................... 18 
3.4 Dose Modifications ................................................................................. 21 
3.5 Supportive Care ....................................................................................... 33 
3.6 Duration of Agent-specific treatment ..................................................... 33 
3.7 Duration of Follow-Up ............................................................................. 33 
4. Study Parameters .............................................................................................. 34 
4.1 Therapeutic Parameters for JNJ-42756493 (Erdafitinib) Treatment ...... 34 
5. Drug Formulation and Procurement ................................................................. 37 
5.1 Erdafitinib (NSC 781558) ......................................................................... 38 
6. Translational Studies ......................................................................................... 41 
7. References ........................................................................................................ 41 
Appendix I  Patient Pill Calendar ............................................................................. 42 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-K2 ............................ 45 
Appendix III  Patient Drug Information Handout and Wallet Card ......................... 51 
 
Rev. Add25

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TREATMENT SUBPROTOCOL CHAIR
Alain Mita, MD
Samuel Oschin Comprehensive Cancer 
Institute
Cedars-Sinai Medical Center
8700 Beverly Boulevard
Mezzanine MS35 PACT 500A
Los Angeles, CA 90048
Phone: (310) 967-0600
Fax: (310) 248-6740
Email: alain.mita@cshs.org
TREATMENT SUBPROTOCOL CO-CHAIR 
Ingrid Mayer, MD
Vanderbilt University
Ingram Cancer Center
2220 Pierce Avenue
777 Preston Research Building
Nashville, TN 37232 6307
Phone: (615) 322-4967
Fax: (615) 343-7602
Email: ingrid.mayer@vumc.org
TRANSLATIONAL CHAIR
Heather Cheng, MD, PhD
University of Washington
825 Eastlake Avenue East
Seattle, WA 98109
Phone: (206) 606-1406
Fax: (206) 606-6681
Email: hhcheng@u.washington.edu

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Schema
Long-Term Follow-Up
JNJ-42756493 (Erdafitinib)
8 mg PO once daily 
*Uptitration to 9mg as per 
protocol guidance 
Until progression or 
unacceptable toxicity
Cycle = 28 days
Accrual Goal: 35
*Refer to Section 3.1

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1.
Introduction
1.1
JNJ-42756493 (erdafitinib)
1.1.1
The FGFR Signaling in Malignancy
The fibroblast growth factor receptors (FGFR) are tyrosine kinases 
that are present in many types of endothelial and tumor cells and are 
shown to play an important role in tumor cell growth, survival, and 
migration as well as in maintaining tumor angiogenesis. Over-
expression of FGFRs, or inappropriate activation through point 
mutation, chromosomal translocation, or aberrant splicing, has been 
implicated in many forms of human malignancies. These FGFR 
abnormalities have been associated with neoplastic progression in 
multiple cancer types, including breast, lung, prostate, endometrial, 
gastric, and urothelial carcinoma. Therefore, targeting FGFRs 
represents an attractive strategy for the development of cancer 
treatment options by simultaneously inhibiting tumor cell growth, 
survival, and migration, as well as tumor angiogenesis. Four different 
FGFRs have been identified: FGFR1, FGFR2, FGFR3, and FGFR4. 
Fibroblast growth factor receptor signaling is activated as a result of 
being bound by fibroblast growth factors (FGFs), their natural ligands. 
The binding of FGF to FGFR results in receptor dimerization and 
subsequent activation of downstream signaling pathways. Activated 
FGFR stimulates tyrosine phosphorylation and activation of a number 
of signaling molecules including FGFR substrate 2 (FRS2). The 
phosphorylation of FRS2 leads to activation of the Grb2/Sos1 
complex and subsequent activation of the mitogen-activated protein 
kinase pathway. This signaling pathway contributes to FGFR-
mediated cell proliferation and migration. The activation of another 
FRS2 downstream pathway, phosphoinositide 3-kinase pathway, is 
involved in cell motility and survival. The FGF/FGFR signaling 
pathway has unequivocally been demonstrated to be important for 
many biological processes critical for the growth of some tumor cells.
1.1.2
JNJ-42756493 (erdafitinib): Structure, Physical Chemical and 
Pharmacological Properties
JNJ-42756493-AAA, referred to as JNJ-42756493, has a molecular 
weight of 446.54 and a molecular formula of C25H30N6O2. The full 
chemical name is N-(3,5-dimethoxyphenyl)-N’-(1-methylethyl)-N[3-(1-
methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine. JNJ-
42756493 has a pKa1 and pKa2 of 9.1 (secondary amine moiety) and 
1.9 (quinoxaline moiety), respectively, and a log P of 4.39 (pH12.0).
JNJ-42756493 is a potent, oral pan-FGFR tyrosine kinase inhibitor 
with IC50 values in the low nanomolar range for all members of the 
FGFR family (FGFR1 to 4). It has demonstrated potent inhibition of 
cell proliferation with IC50 values ranging from <1 to <1000 nM 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 

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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 JNJ-
42756493 has been demonstrated to result in long-term target 
inhibition. JNJ-42756493 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
JNJ-42756493 is supplied as a 1-mg (G-013), a 5-mg (G-014) and a 
20-mg (G015) oral capsules or as 2-mg (G-016), 3-mg (G-017), 4-mg 
(G-019), and 5-mg (G-018) oral film coated tablets. In addition, JNJ-
42756493 oral film-coated tablets with a different coating is being 
developed: 3-mg (G-023), 4-mg (G-024) and 5-mg (G-025).
Additional information may be found in the Investigator’s Brochure.
1.1.3
Animal Pharmacokinetics, Metabolism and Toxicology
JNJ-42756493 showed an intermediate to high permeability in Caco-2
cells and is subject to P-glycoprotein (P-gp) efflux. In animals, JNJ-
42756493 is a high clearance molecule with a moderate volume of 
distribution and a short elimination half-life. Bioavailability of JNJ-
42756493 was low in mice and rats, and high in dogs (when dosed as 
a formulation in 20% hydroxypropyl-β-cyclodextrin (HP-βCD)). The 
bioavailability increased dose dependently due to nonlinear kinetics in 
animals. The nonlinear kinetics is probably due to the saturation of the 
first pass metabolism in animals, and is not observed at clinical doses 
in man. The free fraction in man was between 0.55% and 0.74%. In 
animals, the free fraction ranged from 2.2% (nude rat) to 13.7% (dog). 
JNJ-42756493 is highly boundto α1-acid glycoprotein (α1-AGP). In 
rats, a fast and extensive distribution to the tissues was shown with 
highest tissue exposures being observed in lung and liver. The most 
important metabolic pathways both in vitro in (animal and human) 
hepatocytes and in vivo (rat) were ring closed structures, probably 
resulting from O-demethylation and incorporation of a carbon atom to 
form a seven membered ring (M4 and M7), O-demethylation (M6) 
followed by glucuronidation (M2), and the O-demethylation of M4 and 
M7 (M1), followed by addition of one oxygen (M9). All human 
metabolites were covered by the toxicology species. There was a 
good correlation between the metabolite patterns in vivo and in vitro. 
CYP3A4 can be considered the dominant CYP450 enzyme involved 
in the microsomal metabolism of JNJ-42756493. Other enzymes 
could be involved as well. In both rat and dog, fecal excretion of drug-
related material was higher than urinary excretion. JNJ-42756493 
shows weak inhibition potential towards CYP1A2, CYP2C9, 
CYP2C19, CYP2D6, and CYP3A reflected in IC50 values >15μM. The 
mechanism based inhibition (MBI) potential of JNJ42756493 towards 
CYP3A4 activity was weak.
Good Laboratory Practice (GLP) repeat dose toxicology studies up to 
3 months of duration were conducted in rats and dogs with once daily 
or intermittent administration of JNJ-42756493. The no observed 

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adverse effect level (NOAEL) in the 3-month rat study was 4 
mg/kg/day in males and below 4 mg/kg/day in females based on the 
cornea atrophy and the diffuse atrophy of the exorbital lacrimal gland 
at 4 mg/kg/day in females. At 4 mg/kg/day, JNJ-42756493 Cmax and 
AUC0-24h values were 6.98 ng/mL and 26.3 ng•h/mL in male rats, 
and 13.4 ng/mL and 45.2 ng•h/mL in female rats at the end of the 3-
month treatment period. The NOAEL in the 3-month dog study was 
below 0.5mg/kg/day based on the lacrimal gland atrophy in males and 
females from 0.5 mg/kg/day onwards. At 0.5 mg/kg/day, JNJ-
42756493 Cmax and AUC0-24h values were 21.6 ng/mL and 172 
ng•h/mL in maledogs, and 15.9 ng/mL and 92 ng•h/mL in female dogs 
at the end of the 3-month treatment period. The majority of clinical 
pathology and target organ changes observed in the rat and dog were 
attributed to exaggerated pharmacology of JNJ-42756493 evidenced 
by cartilage (chondroid) dysplasia, soft tissue mineralization and 
atrophy of gland and epithelial structures. Eye-related findings, 
notably thinning of the corneal epithelium (seen in rats) and lacrimal 
gland atrophy (seen in rat and dog), and changes to haircoat and nails 
were only seen in the 3month studies. There was no clear benefit of 
an intermittent (7 days on/7 days off) dosing regimen versus a daily 
dosing regimen in animals. In the 1-month studies, complete recovery 
was seen in the mammary gland (rat) whereas chondroid dysplasia 
and soft tissue mineralizations were shown to be slowly and partially 
reversible; except for the aorta mineralizations in dogs that did not 
show recovery after a 4-week washout period. JNJ-42756493 showed 
no genotoxic potential in the standard panel of GLP genotoxicity tests. 
JNJ-42756493 was classified as a very severe eye irritant at a high 
concentration (20% w/w) in the in vitro bovine corneal opacity and 
permeability (BCOP) test. At clinically relevant concentrations, 
JNJ42756493 did not induce vascular irritation in the standard hen's 
egg chorioallantoic membrane (HETCAM) test in vitro. JNJ-42756493 
was evaluated in mice as having skin sensitizing potential. Although 
JNJ-42756493 exhibited a positive reaction in the 3T3 Neutral Red 
uptake phototoxicity test in vitro, no evidence of cutaneous 
phototoxicity was observed in a pigmented rat study. 
JNJ-42756493 is an intrinsic human ether-à-go-go-related gene 
(hERG) blocker with a proarrhythmic liability, which translates into a 
prolonged repolarization (QTc) after intravenous (i.v.) dosing in the 
anesthetized dog and guinea-pig and after oral (p.o.) dosing in the 
conscious dog. Because clear and consistent effects on QTc were 
found in anesthetized dogs and guinea pigs at levels above 771 
ng/mL (unbound fraction of 81.4 ng/ml), clinical exposures exceeding 
this level will have a substantially increased risk of serious cardiac 
toxicity. In a modified Irwin’s test in rats, JNJ-42756493 showed 
minimal neurofunctional aberrations (impaired wire maneuvers and 
flaccid body tone) from 8 mg/kg (mean Cmax =12.1 ng/mL), 
considered an indirect effect of JNJ-42756493 treatment.

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1.2
Supporting Preliminary Data
1.2.1
First-In-Human Study 
Janssen conducted a phase 1 FIH study in patients with advanced 
cancer, including a subgroup of patients demonstrating FGFR 
aberrations, with several expansion cohorts and 2 schedules (daily 
and a 7 day on, 7 day off schedule).1 The recommended dose on the 
daily schedule was 9 mg; recommended dose on the intermittent 
schedule was 10 mg.  AUC was dose-proportional and apparent T1/2 
was fairly long (50-60h).  Among 23 response-evaluable patients with 
tumor FGFR pathway alterations, four confirmed partial responses 
and one unconfirmed partial response were seen in patients with 
glioblastoma and urothelial and endometrial cancer, all with FGFR2 
and FGFR3 translocations. Median duration of response was 7.2 
months and median PFS was 5.1 months.  Common adverse events 
include hyperphosphatemia (manageable with treatment interruption), 
dry skin and nail toxicities. Drug-related gr≥3 AEs were onycholysis, 
paronychia, and hand-foot syndrome. DLT: 1 at 12 mg (Gr 3 LFT 
elevation).
In this study (Study EDI1001), 125 subjects (98%) experienced a 
TEAE; 68 subjects (54%) experienced a Grade 3 or higher TEAE. The 
5 most common adverse events (35% or greater) in the total 
population are hyperphosphatemia, dry mouth, asthenia, constipation, 
and stomatitis. Other commonly observed effects include skin and nail 
changes, which are considered adverse drug reactions. Grade 3 or 
higher TEAEs were reported for 65 subjects (51%). The most 
common were elevated aspartate aminotransferase and 
hyponatremia, reported for 7 subjects each. Ten (10) subjects (8%) 
had treatment-emergent adverse events that resulted in 
discontinuation of treatment. General physical health deterioration 
was the only event that led to discontinuation by more than 1 subject. 
Adverse events of special interest include events that are class effects 
of FGFR inhibitors and have been experienced by patients treated 
with other FGFR inhibitors. These events include skin, mucosal, and 
nail changes and hyperphosphatemia, fatigue, and reversible retinal 
pigment epithelial detachment (RPED or central serous 
retinopathy[CSR]). Fifty subjects (39%) were reported with serious 
adverse events. The most frequently reported serious events (by 5 or 
more subjects) were general health deterioration, dyspnea, and 
intestinal obstruction. A total of 16 subjects have discontinued from 
Study EDI1001 due to death. Of these, 13 deaths were within 30 days 
of last dose. The primary cause of most deaths within 30 days was 
progressive disease (9/13 subjects). For 3 subjects, the primary cause 
of death was an adverse event. These were not drug related, and 
were anemia and sepsis in 1 subject, pulmonary edema in 1 subject, 
and cerebral hemorrhage in 1subject
In patients, JNJ-42756493 exhibited dose-related increase in Cmax 
and AUC and time-independent PK within the dose range of 0.5 mg to 
12 mg, both after single and multiple daily dosing. Median Tmax 
observed ranged from 2 to 4 hrs (JNJ-42756493 as capsule). JNJ-
42756493 is highly bound to plasma proteins such as α1-Acid 

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Glycoprotein (α1-AGP). In patients, free fractions of JNJ-42756493 in 
human plasma were small (average~0.36%). JNJ-42756493 is a P-
glycoprotein (P-gp) substrate. In vitro data suggested the metabolism 
of JNJ-42756493 was limited, leading to a low amount of metabolites 
being formed. CYP3A4 is the dominant CYP450 enzyme involved. 
Long terminal phase halflife of JNJ-42756493 (>50 hrs) in plasma was 
observed resulting in approximately 3-fold accumulation of Cmax and 
AUC following multiple daily dosing.
1.2.2
Phase 2 Experience
Janssen performed a phase 2 study (NCT02365597) in urothelial 
cancer; (such patients have a reasonably high incidence of alterations 
with FGFR/TACC mutations) and are screened for “certain FGFR 
translocation or mutations at a central lab; the exact variants are not 
public) using 2 dosing regimens.2 Regimen 1 is JNJ-42756493
(erdafitinib) 10 mg dose, 7 days on/7 days off (with option to up-titrate
to 12 mg 7 days on/7 days off) in 28 day cycles; Regimen 2 is JNJ-
42756493 (erdafitinib) 6 mg dose, once daily (with option to up-titrate 
to 8 mg) in 28 day cycles. This resulted in a choice regimen of 8 mg 
daily for 28 days. Thus the RP2D is 8 mg continuously. The study is 
currently ongoing and efficacy results have not been presented. As of 
3 June 2016, 50 subjects have been treated in this study; 24 subjects 
in the 10 mg intermittent dosing regimen and 26 subjects in the 6 mg 
continuous dosing regimen. Twenty (20) subjects have discontinued 
treatment, 7 subjects (14%) due to progression of disease and 5 
subjects (10%) due to adverse events. Thirty (30) subjects (60%) are 
continuing to receive treatment.
Two other studies are currently being conducted in Asian patients 
only, one dose escalation and one phase 2 study in HCC patients. 
Results of these studies are not available.
NOTE:
Please refer to the current IB for the latest information.
1.3
Rationale for 8 mg starting and 9 mg up-titration dose:
Selected dose regimen: Choice of the Sustained Dosing Regimen: 8 mg Daily 
with Flexibility to Up-titrate to 9 mg Daily.
Pharmacokinetics: At the 8 mg dose, based on pharmacokinetic simulations, the 
expected mean unbound Cavg plasma concentrations in patients during the 28 
day cycle period is 3.4 ng/mL. The mean unbound average plasma concentration 
of urothelial cancer patients with clinical activity (partial responses) in the Phase 
1 study was 2.5 ng/mL, which is also consistent with the preclinical target 
window. Antitumor activity is anticipated to correlate with preclinical AUC for 
unbound drug (AUCu), and at the 8 mg dose level, 90% of patients will have 
unbound trough plasma concentrations and AUCu levels within the target window 
(0.6 to 2.4 ng/mL) by Day 3. Thus, 8 mg daily is predicted to generate 
continuously efficacious drug concentrations for the vast majority of patients. 
Pharmacodynamics: Hyperphosphatemia is a common drug-induced toxicity due 
to renal tubular FGFR inhibition and, thus, it can serve as a pharmacodynamics 
marker of drug activity. Dose dependent elevations in serum phosphate occurred 
in all patients starting at 4 mg daily. Because this represents a target-mediated 
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drug effect, one of the Phase 1 study goals was to select a dose regimen that 
consistently induced manageable hyperphosphatemia but did not exceed a 
critical level requiring cessation of therapy, which in the Phase 1 study was 7 
mg/dL. Emerging data from the ongoing Phase 1 study indicates that a 
phosphate increase of at least 35% over baseline level may be associated with 
anti-tumor response. Therefore a pharmacodynamics objective of 50% increase 
in phosphate level over baseline was felt to be appropriate. Considering the 
median phosphate level of 3.6 mg/dL at baseline in the Phase 1 study, and of 3.3 
mg/dL at baseline in the Phase 2 study (IA1 data) an increase of at least 50% for 
the majority of subjects would correspond to an absolute phosphate level of 
around 5.5 g/dL (which is also 35% over the phosphate ULN). Subjects achieving 
a phosphate level of less than 5.5mg/dL by the end of first cycle dosing period 
(day 28) would be considered to have had inadequate PD effect and would be 
candidates for dose escalation to 9 mg daily to achieve an optimum PD effect 
(phosphate range 5.5-7mg/dL).
Overall, emerging pharmacokinetic/pharmacodynamics (PK/PD) modeling 
suggests that approximately 60% of subjects would have serum phosphate levels 
< 5.5 mg/dL (on Day 28) when dosed with 6 mg and would potentially benefit 
from dose up-titration. Additionally, by Day 28 approximately 13% of subjects 
may reach a phosphate level ≥7 mg /dL and thus need an unscheduled 
interruption of up to 7 days to maintain the phosphate level in the target range of 
5.5 to < 7 mg/dL.
Clinical safety: The 8 mg daily dose is the continuous regimen that, based on 
modelling, would likely be well tolerated without significant treatment interruptions 
(approximately 10% to 15% anticipated early interruptions) and for which the 
majority of subjects would tolerate the sustained dose of 8 mg once daily. 
Escalation on Day 15 of the first treatment cycle of daily dose from 8 mg QD to 9 
mg QD in the subjects with both phosphate below 5.5 mg/dL (suboptimal 
pharmacodynamics effect; about 40% of subjects), and without significant drug 
related toxicity (Grade ≥2 toxicity or Grade ≥1 central serious retinopathy or 
retinal pigment epithelial detachments) is unlikely to significantly change the 
overall tolerability profile.
Clinical activity: Assessment of clinical activity at the 6 mg dose and in up-titrated 
subjects at IA1 is limited by the paucity of treated subjects, but 3 PR were 
observed in 14 subjects with phosphate level below 5.5 mg/dL and 4 PR in 7 
subjects with phosphate level over 5.5 mg/dL, pointing to the potential 
importance of attaining full pharmacodynamics effect. Hence the aim is to bring a 
maximal number of subjects within the target phosphate range of 5.5 mg/dL to 
less than 7 mg/dL in order to attain maximal sustained inhibition of target, and 
thereby allow for potential optimization of efficacy, given the observed correlation 
thus far between clinical response and the pharmacodynamics effect on 
phosphate. Selective dose escalation to 9 mg for optimization of the 
pharmacodynamics effect in approximately 40% of subjects is likely to increase 
the potential for clinical activity without significantly increasing dose interruptions 
or toxicity. In addition, the mean dose intensity of the continuous 8 mg regimen 
(with flexibility to up-titrate) based on PK/PD model based simulations is likely to 
be 6.7 mg /day, which would be close to the 6.8 (±2.37) mg/day as observed with 
the 9 mg daily schedule in Phase 1 as compared to the observed 5.4 (± 0.63) 
mg/day reported with the 6 mg daily schedule in Phase 1, thereby increasing the 
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2.
Selection of Patients
Each of the criteria in the checklist that follows must be met, along with the eligibility in 
the MATCH Master Protocol, in order for a patient to be considered eligible for this 
study. Use the checklist to confirm a patient’s eligibility. For each patient, this checklist 
must be photocopied, completed and maintained in the patient’s chart. 
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28. 
ECOG-ACRIN Patient No. ____________________________
Patient’s Initials (L, F, M) _______________________
Physician Signature and Date ___________________
NOTE:
Policy does not allow for the issuance of waivers to any protocol specified 
criteria (http://ctep.cancer.gov/protocolDevelopment/policies deviations.htm). 
Therefore, all eligibility criteria listed in Section 2 must be met, without 
exception. The registration of individuals who do not meet all criteria listed in 
Section 2 can result in the participant being censored from the analysis of the 
study, and the citation of a major protocol violation during an audit. All
questions regarding clarification of eligibility criteria must be directed to the
Group's Executive Officer (EA.Execofficer@jimmy.harvard.edu) or the 
Group's Regulatory Officer (EA.RegOfficer@jimmy.harvard.edu).
NOTE:
Institutions may use the eligibility checklist as source documentation if it has 
been reviewed, signed, and dated prior to registration/randomization by the 
treating physician.
NOTE:
All patients must have signed the relevant treatment consent form
2.1
Registration to Treatment 
2.1.1
Patients must fulfill all eligibility criteria outlined in Section 3.1 of 
MATCH Master Protocol (excluding Section 3.1.6) at the time of 
registration to treatment step (Step 1, 3, 5, 7).
2.1.2
Patients must have FGFR Mutation or Fusion as determined via the 
MATCH Master Protocol and as described in Appendix II. See 
Appendix II for information on the FGFR mutations and corresponding 
Levels of Evidence.
2.1.3
Patients must have an electrocardiogram (ECG) within 8 weeks prior 
to treatment assignment and must have no clinically important 
abnormalities in rhythm, conduction or morphology of resting ECG 
(e.g. complete left bundle branch block, third degree heart block).
Date of ECG:  _______________
2.1.4
Patients must not have known hypersensitivity to JNJ-42756493
(erdafitinib) or compounds of similar chemical or biologic composition.
2.1.5
Patients with current evidence of corneal or retinal 
disorder/keratopathy are excluded.
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2.1.6
Patients must not be currently using medications that can elevate 
serum phosphorous and/or calcium levels.
2.1.6.1
Medications that increase serum calcium should be 
avoided. Over the counter calcium supplements, antacids 
that contain calcium (Tums) and Vitamin D supplements 
(cholecalciferol and ergocalciferol) should be avoided. 
Prescription medications including lithium, 
hydrochlorothiazide and chlorthalidone must be used with 
caution.
2.1.6.2
Medications that increase serum phosphate should be 
avoided. Over the counter laxatives that contain phosphate 
such as Fleets Oral or Fleets enema and Miralax should be 
avoided.
2.1.7
Patients with a history of hyperphosphatemia will be excluded.
2.1.8
Patients may not have received strong inhibitors or potent inducers of
CYP3A within 2 weeks before the first dose of study treatment. 
Patients with inability to discontinue treatment with a strong CYP3A4 
and/or CYP2C9 inhibitor or inducer prior to start of treatment are 
excluded.
2.1.9
Patients who have previously received treatment with a FGFR-
targeted inhibitor are excluded. Such inhibitors include AZD4547,
BGJ398, BAY1163877 and LY2874455). Prior non-selective FGFR 
inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, brivanib,
lucitanib, lenvatinib) are allowed.
2.1.10
Patients must not have any history of or current evidence of renal or 
endocrine alterations of calcium/phosphate homeostasis, or history of 
or current evidence of extensive tissue calcification (by evaluation of 
the clinician), including but not limited to, the soft tissue, kidneys, 
intestine, myocardium and lung with the exception of calcified lymph 
nodes and asymptomatic vascular calcification per investigators’ 
judgment.
2.1.11
Patients with transitional cell carcinoma of the bladder and /or 
urothelial tract are not eligible. These patients are encouraged to 
enroll in the ongoing disease-specific studies.
2.1.12
Patients with impaired renal function (glomerular filtration rate [GFR]
< 60 mL/min) are excluded. GFR should be assessed by direct 
measurement (i.e., creatinine clearance or ethyldediaminetetra-
acetate) or, if not available, by calculation from serum/plasma 
creatinine (Cockcroft-Gault formula).
2.1.13
Patients with persistent phosphate level > ULN during screening 
(within 14 days of treatment and prior to Cycle 1 Day 1) and despite 
medical management are excluded.
2.1.14
Patients with a history of or current uncontrolled cardiovascular 
disease as stated below are excluded:
x
Unstable angina, myocardial infarction, or known congestive heart 
failure Class II-IV within the preceding 12 months; cerebrovascular 
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accident or transient ischemic attack within the preceding 3 
months, pulmonary embolism within the preceding 2 months.
x
Any of the following: sustained ventricular tachycardia, ventricular 
fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second 
degree heart block or third degree heart block; known presence of 
dilated, hypertrophic, or restrictive cardiomyopathy. 
2.1.15
Patients with impaired wound healing capacity defined as 
skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or 
unhealed incisions are excluded.
2.1.16
Female subjects (of child-bearing potential and sexually active) must 
use medically acceptable methods of birth control (hormonal or barrier 
method of birth control; abstinence) prior to study entry, for the 
duration of the study, and for 4 months after the last intake of study 
drug. Male subjects (with a partner of child-bearing potential) must 
use a condom with spermicide when sexually active and must not 
donate sperm from the first dose of study drug until 5 months after the 
last dose of study drug.
Physician Signature
Date
OPTIONAL:
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation.
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following drug administration) can be taken up to 6 hours after the scheduled 
time. If it has been more than 6 hours since the missed dose, then that dose 
should be skipped.
Repeat cycles until progression.
3.2
Adverse Event Reporting Requirements
The Adverse Event Reporting Requirements for all EAY131 subprotocols are 
outlined in the MATCH MASTER protocol.  Please refer to those guidelines when 
determining if an event qualifies as a Serious Adverse Event (SAE) and requires 
expedited reporting via CTEP’s Adverse Event Reporting System (CTEP-AERS).
In addition, the following section outlines agent specific requirements and must 
be followed to ensure all reporting requirements are met.
3.2.1
Additional instructions, requirements and exceptions for protocol 
EAY131 – Subprotocol K2
Additional Instructions
For instructions on how to specifically report events that result in 
persistent or significant disability/incapacity, congenital anomaly, 
or birth defect events via CTEP-AERS, please contact the AEMD 
Help Desk at aemd@tech-res.com or 301-897-7497. This will 
need to be discussed on a case-by-case basis.
EAY131 – Subprotocol K2 specific expedited reporting 
requirements:
x
Pregnancies: Pregnancies and suspected pregnancies 
(including a positive or inconclusive pregnancy test, regardless 
of age or disease state) occurring while the female patient is on 
JNJ-42756493 (erdafitinib), or within 28 days of the female 
patient’s last dose of JNJ-42756493 (erdafitinib), are 
considered immediately reportable events. The pregnancy, 
suspected pregnancy, or positive/ inconclusive pregnancy test 
must be reported via CTEP-AERS within 24 hours of the 
Investigator’s knowledge. Please refer to Appendix VIII in 
MATCH Master Protocol for detailed instructions on how to 
report the occurrence of a pregnancy as well as the outcome of 
all pregnancies.
x
Ocular events: Any grade 3 or higher ocular event of any type 
occurring must be reported via CTEP-AERs in the timeframe 
outlined in Section 5.3.6 of the EAY131 MASTER protocol for 
the specific grade being reported.
x
Liver Events: Any liver adverse event that meets the criteria 
listed below, with no other explanation for the abnormality, 
must be reported via CTEP-AERs in the timeframe outlined in 
Section 5.3.6 of the EAY131 MASTER protocol for the specific 
grade being reported.
x
ALT t 3 x ULN and bilirubin t 2 x ULN (> 35% direct 
bilirubin) (or ALT t 3 x ULN and international normalized 
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ratio [INR] >1.5, if INR measured). Exception to the bilirubin 
elevation is made if the subject has Gilbert’s disease and 
the elevated bilirubin is predominantly unconjugated.
x
ALT t 5 x ULN for 2 weeks or ALT > 8 ULN.
x
ALT t 3 x ULN if associated with the appearance or 
worsening of symptoms of liver injury, hepatitis or 
hypersensitivity such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash or 
eosinophilia.
x
Persistent elevation of ALT t 3 x ULN for t 4 weeks or if 
ALT elevation cannot be monitored.
x
Hy’s law criteria: If the following criteria are met, then it must 
must be reported via CTEP-AERs in the timeframe outlined in 
Section 5.3.6 of the EAY131 MASTER protocol for the specific 
grade being reported
x
(ALT t 3 x ULN and bilirubin ≥ 2 x ULN (> 35% direct 
bilirubin) with no evidence of ALP elevation or ALTt3 x 
ULN and INR >1.5 and no alkaline phosphatase [ALP] 
elevation).
EAY131 – Subprotocol K2 specific expedited reporting 
exceptions:
For Subprotocol K2, the adverse events listed below do not
require expedited reporting via CTEP-AERS:
x
If an AE meets the reporting requirements of the protocol, and 
it is listed on the SPEER, it should ONLY be reported via 
CTEP-AERS if the grade being reported exceeds the grade 
listed in the parentheses next to the event.
3.2.2
Second Primary Cancer Reporting Requirements
All cases of second primary cancers, including acute myeloid 
leukemia (AML) and myelodysplastic syndrome (MDS), that occur 
following treatment on NCI-sponsored trials must be reported to 
ECOG-ACRIN using Medidata Rave
x
A second malignancy is a cancer that is UNRELATED to any 
prior anti-cancer treatment (including the treatment on this 
protocol).  Second malignancies require ONLY routine reporting 
as follows:
1. Complete a Second Primary Form in Medidata Rave within 14 
days.
2. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave confirming the diagnosis.
3. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN
via Medidata Rave.
x
A secondary malignancy is a cancer CAUSED BY any prior anti-
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Secondary malignancies require both routine and expedited 
reporting as follows:
1. Complete a Second Primary Form in Medidata Rave within 14 
days
2. Report the diagnosis via CTEP-AERS at http://ctep.cancer.gov
Report under a.) leukemia secondary to oncology 
chemotherapy, b.) myelodysplastic syndrome, or c.) 
treatment related secondary malignancy
3. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave and submit a copy to NCI/CTEP confirming the 
diagnosis.
4. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN
via Medidata Rave and submit a copy to NCI/CTEP.
NOTE:
The Second Primary Form and the CTEP-AERS report 
should not be used to report recurrence or development of 
metastatic disease.
NOTE:
If a patient has been enrolled in more than one NCI-
sponsored study, the Second Primary Form must be 
submitted for the most recent trial. ECOG-ACRIN must be 
provided with a copy of the form and the associated 
pathology report and cytogenetics report (if available) even 
if ECOG-ACRIN was not the patient's most recent trial.
NOTE:
Once data regarding survival and remission status are no 
longer required by the protocol, no follow-up data should 
be submitted via CTEP-AERS or by the Second Primary 
Form.

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BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and lymphatic system disorders -
Other (lymphadenopathy)
CARDIAC DISORDERS - Sinus tachycardia
EYE DISORDERS - Blurred vision; Eye disorders - Other (blepharitis); Eye disorders - Other 
(blindness unilateral); Eye disorders - Other (corneal erosion); Eye disorders - Other (corneal 
infiltrates); Eye disorders - Other (eyelid edema); Eye disorders - Other (foreign body sensation 
in eyes); Eye disorders - Other (lagophthalmos); Eye disorders - Other (macular degeneration); 
Eye disorders - Other (metamorphopsia); Eye disorders - Other (ocular hyperemia); Eye 
disorders - Other (xanthopsia); Eye pain; Night blindness; Papilledema; Photophobia; Vision 
decreased 
GASTROINTESTINAL DISORDERS - Abdominal distension; Ascites; Colitis; Dysphagia; 
Gastrointestinal disorders - Other (intestinal obstruction); Salivary duct inflammation
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Edema limbs; General 
disorders and administration site conditions - Other (general physical health deterioration); Non-
cardiac chest pain; Pain
INFECTIONS AND INFESTATIONS - Herpes simplex reactivation; Infections and infestations -
Other (clostridum difficile colitis); Infections and infestations - Other (lower respiratory tract 
infection); Infections and infestations - Other (oral herpes); Sepsis; Urinary tract infection
INVESTIGATIONS - Alkaline phosphatase increased; Creatinine increased; GGT increased
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hypercalcemia; 
Hypoalbuminemia; Hypocalcemia; Hyponatremia; Hypophosphatemia
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) -
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other (metastases to 
spine)
NERVOUS SYSTEM DISORDERS - Lethargy; Somnolence
PSYCHIATRIC DISORDERS - Insomnia
RENAL AND URINARY DISORDERS - Acute kidney injury
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Hypoxia; Pleural effusion; 
Respiratory, thoracic and mediastinal disorders - Other (respiratory distress)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Bullous dermatitis; Eczema; 
Hyperkeratosis; Rash maculo-papular; Skin and subcutaneous tissue disorders - Other 
(cutaneous calcification); Skin and subcutaneous tissue disorders - Other (skin exfoliation); Skin 
and subcutaneous tissue disorders - Other (skin lesion); Skin and subcutaneous tissue 
disorders - Other (skin toxicity); Skin atrophy; Skin hyperpigmentation; Skin ulceration
VASCULAR DISORDERS - Hypotension; Thromboembolic event
NOTE:
Erdafitinib (JNJ-42756493) in combination with other agents could cause an
exacerbation of any adverse event currently known to be caused by the other agent, 
or the combination may result in events never previously associated with either 
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3.4
Dose Modifications 
All toxicity grades below are described using the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0.
All appropriate treatment areas should have access to a copy of the CTCAE 
version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the 
CTEP website 
(http://ctep.cancer.gov/protocolDevelopment/electronic applications/ctc.htm)
Dose Modifications and Dose Delays
Treatment can be modified or terminated 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 below.
Table 1:
Dose Modification Guidelines
Toxicity 
Grade 
Action 
Dose Modification After Resolution of 
Adverse Event
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 or 
discontinue
Discontinue*
For general toxicity management:
x
Subjects with any grade of toxicity (Grade 1 to 4) should be provided 
symptomatic treatment when applicable. 
x
Subjects should follow the guidelines in Table 2 for dose reduction 
recommendations and may have more than 1 dose reduction.
x
If JNJ-42756493 (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 JNJ-
42756493 (erdafitinib) should be discontinued with the exception noted 
below.*
x
If the subject achieves calcium-phosphate product > 70 mg2/dL2 for 2 
consecutive weeks despite phosphate lowering therapy or > 90 mg2/dL2 any 
time during treatment despite phosphate lowering therapy, JNJ-42756493 
(erdafitinib) should be withheld until recovery to calcium-phosphate product 
< 55 mg2/dL2. Treatment may be reintroduced at the first reduced dose level.
x
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 be carefully 
monitored, and supportive therapy administered, where applicable. Dose 
administration may be restarted when it is considered safe and at an 
appropriate dose, according to the investigator’s assessment.
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to 2 times weekly until resolution, stabilization, or return to subject’s baseline 
values. Monitor clinical condition closely.
x
Record use of concomitant medications, acetaminophen, herbal remedies, 
other over-the-counter medications, or known hepatotoxins.
x
Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH).
x
Check the viral hepatitis serology as appropriate and include:
x
Hepatitis A IgM antibody;
x
Hepatitis B surface antigen and Hepatitis B core antibody (IgM);
x
Hepatitis C RNA; 
x
Hepatitis E IgM antibody ( appropriate for subjects traveling outside North 
America);
x
Cytomegalovirus IgM antibody; and 
x
Epstein-Barr viral capsid antigen IgM antibody (or equivalent test). 
x
Anti-nuclear antibody, anti-smooth muscle antibody, and type 1 anti-liver 
kidney microsomal antibodies 
x
Liver imaging (ultrasound, magnetic resonance, or computerized 
tomography) to evaluate liver disease
Liver Event Re-challenge Requirements
If a subject meets the liver event stopping criteria, the study drug should not be 
re-administered. In the case in which Hy’s law is not met and the investigator can 
demonstrate that re-introduction of study drug is in the best interest of the subject 
considering the terminal nature of the disease, the drug may be re-introduced at 
a lower dose and/or intensity if the study chair is in agreement with this 
assessment. With appropriate re-consenting, the subject can be retreated with a 
1- or 2-dose level reduction as appropriate, along with appropriate clinical follow-
up as designated by the investigator. Prior to re-introduction, the investigator 
should obtain written permission from the study chair and the IRB. The 
investigator should also have the subject re-consent, explaining that re-
introduction of study drug could lead to liver damage, which may be serious 
and/or may even result in death.
Guidelines for the Management of Elevated Phosphate Levels

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Guidelines for the clinical management of elevated serum phosphate levels are 
presented in Table 3.
Table 3:
Guidelines for Management of Serum Phosphate Elevation
Serum Phosphate 
Level
Study Drug Management
Medical Management
All subjects in the 
study
Continue JNJ-42756493 (erdafitinib) 
treatment.
Restriction of phosphate 
intake to 600 – 800 mg/day.
5.5-6.9 mg/dL
(1.8-2.2 mmol/L)
Continue JNJ-42756493 (erdafitinib) 
treatment.
Restriction of phosphate 
intake to 600 – 800 mg/day.
May consider sevelamer 800 
mg to 1,600 mg 3 times a day 
(with food)
7.0-9.0 mg/dL
(2.3-2.9 mmol/L)
Withhold a JNJ-42756493 (erdafitinib) 
treatment until serum phosphate level returns 
to < 5.5 mg/dL. 
Re-start treatment at the same dose level. 
A dose reduction may be implemented for 
persistent b hyperphosphatemia (≥7 mg/dL) if 
clinically necessary 
Restriction of phosphate 
intake to 600 – 800 mg/day.
Sevelamer 800 to 1,600 mg 3 
times a day with food until 
phosphate level is < 5.5
mg/dL.
> 9.0 mg/dL
(> 2.9 mmol/L)
Withhold a JNJ-42756493 (erdafitinib) 
treatment until serum phosphate level returns 
to < 5.5 mg/dL. 
Re-start treatment at the first reduced dose 
level. 
A second dose reduction may be 
implemented if needed or clinically indicated 
for persistent b hyperphosphatemia (≥7
mg/dL) at every cycle 
Restriction of phosphate 
intake to 600 – 800 mg/day.
Sevelamer up to 1,600 mg 3 
times a day with food
AND 
Acetazolamide 250 mg 2 or 3 
times a day only until serum 
phosphate level returns to <
5.5 mg/dL.
> 10.0 mg/dL (> 3.2 
mmol/L) and/or 
significant alteration 
in baseline renal 
function and/or 
Grade 3 
hypocalcemia
JNJ-42756493 (erdafitinib) should be 
discontinued permanently. (In situations 
where the subject is having clinical benefit 
and the investigator and the sponsor’s study 
chair agree that re-starting drug is in the best 
interest of the subject, the drug may be re-
introduced at 2 dose levels lower if 
appropriatec. 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 and/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 (nonǦcalcium 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 the National Kidney 
Foundation website (http://www.kidney.org/atoz/content/phosphorus.cfm)

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a Drug interruptions for hyperphosphatemia suggested to be 7 days duration
b Persistent hyperphosphatemia is considered to be more than 1 sequential phosphate value of >=7 
mg/dL
c
If a subject has been deriving benefit from treatment, and the investigator can demonstrate that re-
introduction of study drug is in the best interest of the subject considering the terminal nature of the 
disease, the drug may be re-introduced at a lower dose and/or intensity if the study chair is in 
agreement with this assessment. With appropriate re-consenting, the subject can be retreated with 
a 1- or 2-dose level reduction as appropriate, along with appropriate clinical follow-up as 
designated by the investigator. Prior to re-introduction, the investigator should obtain written 
permission from the study study chair and the IRB. The investigator should also have the subject 
re-consent, explaining that re-introduction of study drug could lead to increased risk of recurrent 
toxicities. (please see Section 16.2.3 for details).
Guidelines for the Management of Dry Mouth and Stomatitis
Guidelines for the clinical management of dry mouth (xerostomia) and stomatitis 
are provided in Table 4 and Table 5, respectively. 
x
General Prophylaxis: 
x
Good oral hygiene
x
Use a soft toothbrush
x
Avoidance of spicy, acidic, hard, and hot food and beverages
x
Use of mild-flavored toothpastes
x
Use of saline-peroxide or salt and soda mouthwashes 3 or 4 times per 
day
x
Water soluble lubrication agents like artificial saliva (for xerostomia or dry 
mouth)

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Table 4:
Guidelines for the Management of Dry Mouth (Xerostomia)
Grade and Definition
Study Drug 
Management
Medical 
Management 
Grade 1: symptomatic (e.g., dry 
or thick saliva) without 
significant dietary alteration; 
unstimulated saliva flow 
>0.2 mL/min
Continue study drug 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 study drug at 
current dose.  
Sorbitol lozenges 
PRN and Cevimeline 
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 study drug (for up to 
28 days), with weekly 
reassessments of clinical 
condition.
When resolved to 
≤Grade 1 or baseline, 
restart at 1 dose level 
below in consultation with 
the study chair.
Sorbitol lozenges 
PRN and Cevimeline 
30 mg TID or 
Pilocarpine 5 mg TID
Grade 4: life-threatening 
consequences, urgent 
intervention indicated
Discontinue study drug.  
Evaluation and 
therapy as clinically 
indicated

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Table 5:
Guidelines for the Management of Mucositis
Grade and Definition
Study Drug Management
Medical 
Management 
Grade 1: Asymptomatic 
or mild symptoms; 
interventions not 
indicated
Continue study drug at current 
dose.
Topical steroid 
moderate strength 
and lidocaine 2-5%
jelly or solution QID
Grade 2: Moderate pain 
or ulcer that does not 
interfere with oral 
intake; modified diet 
indicated
Continue study drug at current 
dose.  
Consider study drug holding if no 
improvement in 1 week.
When resolves to ≤Grade 1 or 
baseline, restart at same or 1 
dose level below in consultation 
with the study chair.
Dexamethasone 
solution 
(3.3 mg/5 mL) swish 
and spit QID and 
lidocaine 2-5% jelly or 
solution QID
Grade 3: Severe pain; 
interfering with oral 
intake
Hold study drug (for up to 28 
days), with weekly reassessments 
of clinical condition. 
When resolves to ≤Grade 1 or 
baseline, restart at 1 dose level 
below in consultation with the 
study chair.
Dexamethasone 
solution 
(3.3 mg/5 mL) swish 
and spit QID and 
lidocaine 2-5% jelly or 
solution QID
Grade 4: life threatening 
consequences, urgent 
intervention indicated
Discontinue study drug.  
Evaluation and 
therapy as clinically 
indicated
Guidelines for the Management of Dry Skin and Skin Toxicity
Guidelines for the management of dry skin are provided in Table 6.
x
General prophylaxis:
x
Avoid unnecessary exposure to sunlight and excessive use of soap.
x
Avoid bathing in excess; use tepid rather than hot water.  
x
Use moisturizers regularly; apply thick, alcohol-free and oil-in-water 
based emollient cream on exposed and dry areas of the body.  
x
Avoid perfumed products, bubble bath, perfumed soaps, and take breaks 
from shaving.  
x
Use broad spectrum sunscreen with a skin protection factor (SPF) ≥15.
x
Wear cotton clothes next to skin rather than wool, synthetic fibers, or 
rough clothing.
x
Use occlusive alcohol-free emollient creams (jar or tub) for treatment of 
mild/moderate xerosis.
x
For scaly areas, use exfoliants (ammonium lactate 12% or lactic acid 
cream 12%).

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Table 6:
Guidelines for Management of Dry Skin
Grade and Definition
Study Drug 
Management
Medical Management 
Grade 1: Dry skin 
covering less than 10% 
body surface area (BSA) 
and no associated 
erythema or pruritus
Continue study drug at 
current dose.  
Use fragrance free 
moisturizing cream or 
ointment BID over entire body.
Use ammonium lactate 12% 
cream or salicylic acid 6% 
cream BID over 
dry/scaly/hyperkeratotic areas 
such as palms and soles.
Grade 2: Dry skin 
covering 10 to 30% BSA 
and associated with 
erythema or pruritis with 
limited instrumental 
activities of daily living 
(IADL)
Continue study drug at 
current dose. 
Use fragrance free 
moisturizing cream or 
ointment BID over entire body.
Use ammonium lactate 12% 
cream or salicylic acid 6% 
cream BID over 
dry/scaly/hyperkeratotic areas 
such as palms and soles.
Use zinc oxide 13-40% at 
night for areas with fissures.
Grade 3: Dry skin 
covering > 30% BSA and 
associated with pruritis; 
limiting self-care activities 
of daily living (ADL)
Hold study drug (for up 
to 28 days), with weekly 
reassessments of 
clinical condition.
When resolves to 
≤ Grade 1 or baseline, 
restart at 1 dose level 
below in consultation 
with the study chair.
Use topical steroid ointment or 
cream* BID and zinc oxide 13-
40% at night for areas with 
fissures.
Grade 4: Dry skin with 
life-threatening 
consequences, urgent 
intervention indicated
Discontinue study drug.  
Evaluation and therapy as 
clinically indicated
* Topical Steroid Ointments: Clobetasol 0.05%, Betamethasone 0.05%, Fluocinonide 
0.05%
Guidelines for Management of Nail Toxicity (Onycholysis, Onychodystrophy, and 
Paronychia)
Guidelines for management of nail discoloration/loss/ridging 
(onycholysis/onychodystrophy) are provided in Table . Guidelines for the 
management of paronychia are provided in Table .
x
General Prophylaxis: 
x
Good hygienic practices, keep fingers and toes clean.
x
Keep nails trimmed
x
Use gloves for housecleaning and gardening to minimize damage and 
prevent infection
x
Nail polish and imitation fingernails should not be worn until the nails have 
grown out and returned to normal

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x
Wearing comfortable shoes (wide sized shoes with room for the toes)
x
Trimming nails but avoiding aggressive manicuring
Table 7:
Guidelines for Management of Nail Discoloration/Loss/Ridging 
(Onycholysis/Onychodystrophy)
Grade and Definition
Study Drug 
Management
Medical Management
Grade 1: Asymptomatic; 
clinical or diagnostic 
observations only
Continue study drug at 
current dose,
Over the counter nail strengthener OR 
poly-urea urethane nail lacquer (Nuvail) 
OR diethylene glycol monoethylether nail 
lacquer daily (Genadur) 
Grade 2: Symptomatic 
separation of the nail bed 
from the nail plate or nail 
loss, limiting instrumental 
ADLs
Continue study drug at 
current dose. 
Consider study drug 
holding if no improvement 
in 1 to 2 weeks.
When resolves to 
≤Grade 1 or baseline, 
restart at same or 1 dose 
level below in consultation 
with the study chair.
For signs of infection (periungal 
edema/erythema/ tenderness and/or 
discharge), obtain bacterial cultures, and 
then start the following:  
x treatment with oral antibiotic for 2 weeks 
(cefadroxil 500 mg BID, ciprofloxacin 
500 mg BID, or sulfamethoxazole/ 
trimethoprim (Bactrim®) DS BID) 
AND 
x topical antifungal lacquer daily for 6+ 
weeks (ciclopirox olamine 8% OR 
efinaconazole 10% OR amorolfine 5% 
weekly OR bifonazole/urea ointment 
daily)
Grade 3:  Severe nail tip 
pain, symptomatic 
separation of the nail bed 
from the nail plate or nail 
loss, significantly limiting 
IADLs
Hold study drug (for up to 
28 days), with weekly 
reassessments of clinical 
condition. 
When resolves to ≤Grade 
1 or baseline, restart at 1 
dose level below in 
consultation with the 
study chair.
Silver nitrate application weekly AND 
topical antibiotics AND vinegar soaks.a
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 study drug
Evaluation and therapy as clinically 
indicated
aVinegar soaks consist of soaking fingers or toes in a solution of white vinegar in water 1:1 for 15 
minutes every day. Examples of topical antibiotic ointments: Mupirocin 2%, gentamycin, bacitracin 
zinc/polymixin B

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Table 8:
Guidelines for Management of Paronychia
Grade and Definition
Study Drug Management
Medical Management
Grade 1: Nail fold edema or 
erythema; disruption of the 
cuticle
Continue study drug 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 study drug at current 
dose. 
Consider study drug holding if 
no improvement in 1 to 2 
weeks.
When resolves to ≤Grade 1 or 
baseline, restart at same or 1 
dose level below in 
consultation with the study 
chair.
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: Operative 
intervention indicated; IV 
antibiotics indicated; limiting 
self care ADL
Hold study drug (for up to 28 
days), with weekly 
reassessments of clinical 
condition.
When resolves to ≤ grade 1 or 
base line, restart at one dose 
level below in consultation with 
the study chair.
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 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
Guidelines for Eye Toxicity Associated With Vision Changes
If a subject experiences an event of confirmed new corneal or retinal abnormality 
while on study drug, the event should be reported as an adverse event of special 
interest (if Grade 1 or 2) or a serious adverse event (if Grade 3 or higher) as 
appropriate. Any new and clinically significant symptoms, such as but not limited 
to, blurred vision, partial or complete loss of vision, double vision, floaters or color 
spots or halos around light, change in color or night vision, photophobia, ocular

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pain or stinging sensation, or foreign body sensation should be further evaluated 
and managed per the guidelines below.
All subjects should have monthly Amsler grid tests and an initial ophthalmological 
examination performed at Screening by an ophthalmologist, which should include 
assessment of visual acuity, tonometry, fundoscopy (examination of both central 
and peripheral zones should be performed); where available, an Optical 
Coherence Tomography (OCT) should be performed. A follow-up
ophthalmological examination should be performed as clinically necessary based 
on the findings of the monthly Amsler grid tests*** and clinical assessment. It is
assumed that about 30% patients will require follow-up full ophthalmological 
examinations.
If 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 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.
*** 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.
Table 9:
Guidelines for Management of Eye Toxicity
Grade and Definition
Study Drug Management
Medical Management
Grade 1: 
Asymptomatic or mild 
symptoms; clinical or 
diagnostic 
observations only
Or abnormal Amsler 
grid test 
Refer for an ophthalmologic examination. If an 
ophthalmologic exam cannot be performed within 7 
days, withhold treatment of JNJ-42756493 until an 
examination can be performed.
If there is no evidence of eye toxicity on 
ophthalmologic examination, continue JNJ-42756493 
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 JNJ-42756493 until 
signs and symptoms have resolved.
If toxicity is reversible (complete resolution or
stabilization and asymptomatic) in 4 weeks according 
to ophthalmologic examination, resume JNJ-
42756493 therapy at the next lower dose level after 
consultation with the study chair.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 study chair.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. 

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Grade and Definition
Study Drug Management
Medical Management
Grade 2: Moderate; 
minimal, local
or noninvasive 
intervention indicated; 
limiting age 
appropriate 
instrumental ADL
Grade 3: Severe or 
medically significant 
but not immediate 
sight-threatening; 
hospitalization or 
prolongation of 
existing hospitalization 
indicated; disabling; 
limiting self-care ADL
Immediately withhold JNJ-42756493 therapy.  
If there is no evidence of drug-related corneal or 
retinal pathology on ophthalmologic examination, 
withhold JNJ-42756493 until signs and symptoms 
have resolved. Resume JNJ-42756493 therapy at the 
next lower dose level.
If diagnosis from ophthalmologic examination is 
keratitis or retinal abnormality such as CSR/RPED, 
withhold JNJ-42756493 until signs and symptoms 
have resolved, stabilized, or subject is lost to follow-up 
or withdraws consent (which ever happens first).
If toxicity is Grade 2 and reversible (complete 
resolution or stabilization and asymptomatic) within 4 
weeks according to ophthalmologic examination, 
resume JNJ-42756493 therapy at the next lower dose 
level after consultation with the study chair.
If the toxicity is Grade 3, report as a serious adverse 
event and permanently discontinue JNJ-42756493. If 
however the toxicity is Grade 3 and reversible 
(complete resolution or stabilization and 
asymptomatic) within 4 weeks and the subject is 
having clinical benefit, and the investigator and the 
sponsor’s study chair agree that re-starting drug is in 
the best interest of the subject, then JNJ-42756493 
therapy may be resumed at 2 dose levels lower if 
appropriate.a Monitor for recurrence using appropriate 
investigations every 1 to 2 weeks for a month and as 
clinically appropriate thereafter. For cases of 
recurrence consider permanent discontinuation.
Refer subject to an 
ophthalmologist for 
evaluation with an 
ophthalmologic 
examination.
For retinal pathology, 
perform OCT as 
appropriate and 
consider referral to a 
retinal specialist for 
further evaluation. 
Follow specific 
treatment per the 
ophthalmologist’s 
recommendation. 
Grade 4: Sight-
threatening 
consequences; urgent 
intervention indicated; 
blindness (20/200 or 
worse) in the affected 
eye
Permanently discontinue treatment with JNJ-
42756493. 
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. 
a If a subject has been deriving benefit from treatment, and the investigator can demonstrate that re-
introduction of study drug is in the best interest of the subject considering the terminal nature of the 
disease, the drug may be re-introduced at a lower dose and/or intensity if the study chair is in agreement 
with this assessment. With appropriate re-consenting, the subject can be retreated with a 1- or 2-dose 
level reduction as appropriate, along with appropriate clinical follow-up as designated by the investigator.
Prior to re-introduction, the investigator should obtain written permission from the study chair and the 
IRB. The investigator should also have the subject re-consent, explaining that re-introduction of study 
drug could lead to increased risk of recurrence. (Please see Section 16.2.3 for details)
Guidelines for the Management of Dry Eye
x
General considerations: Avoid unnecessary exposure to sunlight, use 
sunglasses in bright light.
x
Prophylactic management: Frequent use of artificial tear substitutes is 
strongly recommended.

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x
Reactive management:
x
Withhold JNJ-42756493 for Grade 3 toxicity 
x
Artificial tear substitutes if not started, every 4 to 6 hours
x
Hydrating /lubricating eye gels and ointments 
x
Severe treatment-related dry eye should be evaluated by an 
ophthalmologist 
3.5
Supportive Care 
All supportive measures consistent with optimal patient care will be given 
throughout the study.
3.6
Duration of Agent-specific treatment 
In the absence of treatment delays due to adverse event(s), treatment may 
continue until one of the following criteria applies:
x
Extraordinary Medical Circumstances: If at any time the constraints of this 
protocol are detrimental to the patient's health, protocol treatment should be 
discontinued. In this event submit forms according to the instructions in the 
MATCH Forms Packet.
x
Patient withdraws consent.
x
Patient experiences unacceptable toxicity.
x
Non-protocol therapies are administered.
x
Disease progression
3.7
Duration of Follow-Up
Refer to the MATCH Master Protocol for specifics on the duration of follow-up.

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4.
Study Parameters
4.1
Therapeutic Parameters for JNJ-42756493 (Erdafitinib) Treatment
NOTE:
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving JNJ-42756493 (erdafitinib) treatment.
NOTE:
All assessments required prior to registration to treatment should be done ≤4 weeks prior to registration to 
Steps 1, 3, 5, 7, excluding the radiologic evaluation and electrocardiogram (ECG).
Test/Assessment
Prior to 
Registration to 
Treatment
Treatment
End of 
Treatment
Follow UpF
Every Cycle, 
prior to 
treatment
Cycle 1 Day 
15
Every 2 
Cycles
H&P, Weight, Vital signsA
X
XJ
X
X
Performance status
X
XJ
X
X
CBC w/diff, pltsB
X
XJ
X
X
Serum chemistryB
X
XJ
X
X
Radiologic evaluationD
X
XD
XF
E-HCGC
X
Toxicity AssessmentG
X
X
X
XF
Pill Count/DiaryH
X
X
ECGK
X
XI
Ophthalmologic examL
X
X
X
Phosphate LevelsM
X
Tumor biopsy and blood sample for MATCH Master ProtocolE
X
X
A. History and physical, including vital signs and weight at the start of each cycle (up to 3 days before start of new cycle).
B. Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, creatinine, glucose, phosphorus, potassium,  SGOT[AST], SGPT[ALT], 
sodium, magnesium and serum tumor markers (including LDH, PSA if appropriate). Serum tumor markers are not required on Cycle 1, Day 15.
For eligibility purposes, participants with creatinine levels above institutional normal, Cockcroft-Gault will be used to calculate creatinine clearance.
CBC w/diff, platelets and serum chemistries should be performed on cycle 1, day 1 (or up to 7 days prior), and at the start of each subsequent 
cycle (up to 3 days before start of new cycle). CBC with differential will be performed more frequently in patients with grade 4 neutropenia or 
thrombocytopenia until resolution to ≤ grade 3. CBC and serum chemistries are only required in follow-up until values return to pre-treatment levels 
or until progressive disease.
Rev. Add16

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C. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment.
D. Disease measurements are repeated every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until PD or start of another MATCH 
treatment step. The baseline evaluation should be performed as closely as possible to the beginning of treatment and never more than 6 weeks 
before registration to treatment step. For multiple myeloma patients, please refer to Section 6.4 of the MATCH Master Protocol for additional 
information on myeloma response criteria and the required disease assessments. Documentation (radiologic) must be provided for patients 
removed from study for progressive disease.
E. Additional blood specimens and/or biopsies are to be submitted from consenting patients per Section 9.3.2 of the MATCH Master Protocol. Submit 
at the following time points, as applicable:
x
Blood specimens are to be submitted at the end of Cycle 2 (prior to start of Cycle 3 treatment). If patient progresses or treatment is 
discontinued prior to Cycle 3, collect the blood at that time instead. On-treatment kits for blood sample collections will be automatically shipped 
to sites upon registration to the treatment step.
x
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4).
x
At end of all MATCH study treatments, blood specimens and/or research biopsy after consent and registration to Step 8
Please refer to Section 4 of the MATCH Master Protocol to determine whether the patient proceeds to the next screening step or to follow-up (with 
a potential end of treatment biopsy for research purposes on Step 8). Samples are to be submitted as outlined in Section 9 of the MATCH Master 
Protocol. To order Step 2/4 Screening or Step 8 kits, complete the EAY131 Collection and Shipping Kit Order Form (See Appendix XII of the 
MATCH Master Protocol) and fax to 713-563-6506.
F. Every 3 months if patient is < 2 years from study entry, and every 6 months for year 3. Toxicity assessments and radiologic evaluations are not 
required to be done during Follow Up if progression has been previously reported; however if an adverse event occurs post treatment that meets 
the SAE reporting requirements, it still must be reported via CTEP-AERS, even if progression has occurred.
G. Site personnel should evaluate for toxicity and discuss treatment compliance with the patient in order to ensure the medication is taken correctly; 
this evaluation must be conducted in person. The Toxicity Assessment is not required prior to Cycle 1, but is required on cycle 1 day 1, cycle 1 day 
15 and on day 1 of every subsequent cycle.
H. The pill calendar will be collected at the end of every cycle. The Pill Count/Diary is not required prior to Cycle 1, but is required every subsequent 
cycle.
I. As clinically indicated.
J. For Cycle 1, if the following tests/assessments occurred within 7 days of Day 1, they do not need to be repeated at this timepoint: H&P, Weight, 
Vital Signs; Performance Status; CBC w/diff, plts; Serum chemistry; Concomitant Medications.
K. Within 8 weeks of treatment assignment.
L. All subjects should have monthly Amsler grid tests and an initial ophthalmological examination performed at Screening by an ophthalmologist, 
which should include assessment of visual acuity, tonometry, fundoscopy (examination of both central and peripheral zones should be performed); 
where available, an Optical Coherence Tomography (OCT) should be performed. A follow-up ophthalmological examination should be performed 
as clinically necessary based on the findings of the monthly Amsler grid tests and clinical assessment. It is assumed that about 30% patients will 
require follow-up ophthalmological examinations.\
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 

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that color 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 on Day 1 of each 28-day cycle. 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.
M.For subjects, treatment will be up-titrated or maintained based on phosphate level measured on Cycle 1 Day 15, and taking into account observed 
toxicity to that day, as described in Figure 1. The up-titrated dose would be given starting on Cycle 1 Day 15.

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5.
Drug Formulation and Procurement
This information has been prepared by the ECOG-ACRIN Pharmacy and Nursing 
Committees.
Availability
NO STARTER SUPPLIES MAY BE ORDERED. Subjects must be enrolled and assigned 
to the treatment subprotocol prior to submitting the clinical drug request to PMB.
Ordering instructions for Cycle 1:
Once a patient is registered to Arm K2, the site should request Cycle 1 supplies through 
OAOP consisting of the following:
x
2 bottles of 4 mg tablets and 2 bottles of 3 mg tablets
This quantity provides enough JNJ42756493 (erdafitinib) to complete Cycle 1 at either 
the:
x
Starting dose of 8 mg on Days 1 - 28, or
x
Starting dose of 8 mg on Days 1 – 14 and the up-titrated dose of 9 mg on Days 15 –
28.
Once it is determined whether the patient’s dose will be up-titrated following completion 
of the Day 15 evaluation (including the patient’s phosphate based on Sections 3 and 
4.1), a clinical drug request for the appropriate Cycle 2+ supplies should be submitted in 
OAOP per the usual ordering procedure.
Drug Ordering: NCI supplied agents may be requested by eligible participating 
Investigators (or their authorized designee) at each participating institution. 
Pharmaceutical Management Branch (PMB) policy requires that drug be shipped directly 
to the institution where the patient is to be treated. PMB does not permit the transfer of 
agents between institutions (unless prior approval from PMB is obtained – see general 
information) The CTEP-assigned protocol number must be used for ordering all CTEP-
supplied investigational agents. The eligible participating investigators at each 
participating institution must be registered with CTEP, DCTD through an annual 
submission of FDA Form 1572 (Statement of Investigator), NCI Biosketch, Agent 
Shipment Form, and Financial Disclosure Form (FDF). If there are several participating 
investigators at one institution, CTEP-supplied investigational agents for the study 
should be ordered under the name of one lead investigator at that institution.
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 
application (https://ctepcore.nci.nih.gov/OAOP). Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account 
(https://ctepcore.nci.nih.gov/iam/) and the maintenance of an “active” account status, a
“current” password, and an active person registration status.
NCI Supplied Agent(s) – General Information
Questions about drug orders, transfers, returns, or accountability should be 
addressed to the PMB by calling 240-276-6575 Monday through Friday between 
8:30 AM and 4:30 PM Eastern Time or email PMBAfterHours@mail.nih.gov anytime.
Drug Returns: All undispensed drug supplies should be returned to the PMB. When it is 
necessary to return study drug (e.g., sealed bottles remaining when PMB sends a stock 
recovery letter), investigators should return the study drug to the PMB using the NCI 
Return Agent Form available on the NCI home page (http://ctep.cancer.gov).
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Drug Accountability: The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the receipt, disposition, and return of 
agent received from the PMB using the NCI Investigational Agent Accountability Record 
Form for Oral Agents available on the NCI home page (http://ctep.cancer.gov). Maintain 
separate NCI Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator on this protocol.
Investigator Brochure Availability: The current versions of the IBs for PMB-supplied 
agents will be accessible to site investigators and research staff through the PMB Online 
Agent Order Processing (OAOP) application. Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account and the 
maintenance of an “active” account status, a “current” password, and active person 
registration status. Questions about IB access may be directed to the PMB IB 
coordinator at IBCoordinator@mail.nih.gov.
5.1
Erdafitinib (NSC 781558)
5.1.1
Other Names:
JNJ-42756493
5.1.2
Classification:
pan-FGFR tyrosine kinase inhibitor
5.1.3
Mode of Action:
Erdafitinib is an oral pan-FGFR tyrosine kinase inhibitor that has 
demonstrated potent inhibition of cell proliferation in FGFR pathway-
activated cancer cell lines.
5.1.4
Storage and Stability:
Storage: Store intact bottles at controlled room temperature 15°C to 
30°C (59 to 86°F). 
If a storage temperature excursion is identified, promptly return 
erdafitinib to 15°C to 30°C and quarantine the supplies.  Provide a 
detailed report of the excursion (including documentation of 
temperature monitoring and duration of the excursion) to 
PMBAfterHours@mail.nih.gov for determination of suitability.
Stability: Shelf life dating is printed on the bottle label.
5.1.5
Dose Specifics:
Erdafitinib tablets will be administered orally once a day on a 
continuous daily dosing schedule on a 28-day cycle. Dose reductions 
are allowed according to Section 3.4.
JNJ-42756493 (erdafitinib) dose
Use tablet strengths
8 mg
2 x 4 mg 
6 mg
2 x 3 mg
9 mg
3 x 3 mg
5.1.6
How Supplied:
Johnson & Johnson supplies and CTEP, NCI, DCTD distributes JNJ-
42756493.  The agent is available as 3 mg (yellow), 4 mg (orange), 

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and 5 mg (brown) film coated tablets.  The approximate dimensions of 
the round tablets are in the table below:
Strength
Diameter (mm)
Thickness (width) (mm)
3 mg
7.7 + 0.2
3.7 + 0.4
4 mg
8.2 + 0.2
4.2 + 0.4
5 mg
8.7 + 0.2
4.6 + 0.4
Erdafitinib tablets are provided in 30 count bottles made of high 
density polyethylene (HDPE), with an induction seal and child 
resistant cap. Tablets must be dispensed in the original container.
Tablet excipients include mannitol, microcrystalline cellulose, 
meglumine, croscarmellose sodium, magnesium stearate, and Opadry 
AMB II.
5.1.7
Route of Administration:
Oral. Take tablets at least 1 hour before eating or at least 2 hours 
after a meal at approximately the same time each day. Tablets must 
be swallowed whole with 8 ounces of water. Do not crush or chew.
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.
5.1.8
Incompatibilities: 
Erdafitinib shows weak inhibition potential towards CYP1A2, CYP2C9, 
CYP2C19, CYP2D6, and CYP3A4. No clinical studies have been 
conducted yet for erdafitinib regarding the potential for drug-drug 
interactions in humans. 
CYP3A4 and CYP2C9 can be considered the dominant CYP450 
enzymes involved in the microsomal metabolism of erdafitinib. With 
CYP2D6 and CYP2C8 can potentially be involved to a minor extent. 
Caution is to be exercised in combining erdafitinib with strong 
inhibitors/inducers of CYP3A4/5 and CYP2C9. Subjects should be 
closely monitored for potential toxicities, and appropriate action, 
including temporary interruption of erdafitinib, as appropriate should 
be taken.
Erdafitinib has intermediate to high permeability with some indication 
of a P-glycoprotein (P-gp) efflux mechanism. Potent inhibitors of P-gp 
should be contraindicated.
5.1.9
Side Effects: 
See Section 3.3 for side-effects
5.1.10
Nursing/Patient Implications 
Female subjects (of child-bearing potential and sexually active) must 
use medically acceptable methods of birth control prior to study entry 
and for the duration of the study, and for 4 months after the last intake 

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of study drug. Male subjects (with a partner of child-bearing potential) 
must use a condom with spermicide when sexually active and must 
not donate sperm from the first dose of study drug until 5 months after 
the last dose of study drug.
Medically acceptable methods of contraception that may be used by 
the subject and/or his/her partner include hormonal prescription oral 
contraceptives, contraceptive injections, contraceptive patch, 
intrauterine device, true sexual abstinence, and surgical sterilization 
(eg, 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 4 months for females and 5 months for males 
after the last dose of study drug is given.
No clinically significant QT prolongation or cardiovascular effects have 
been noted to date. However, consistent QT prolongation was seen 
across several species in nonclinical studies. Concomitant 
administration of medications that induce QTc should be used with 
caution.
All subjects should be closely monitored with special attention to 
cardiovascular function and evidence of disturbance of phosphate 
homeostasis and bone pathology and ocular symptoms until sufficient 
clinical experience is obtained.
Ophthalmological testing should be performed once during screening. 
Additional exams should be performed as clinically necessary.
Acid lowering agents (eg, antacids, H2-antagonists, or proton pump 
inhibitors) are not expected to affect the bioavailability of erdafitinib. 
Erdafitinib may be co-administered with an acid lowering agent.

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6.
Translational Studies
Please refer to the MATCH Master Protocol for information on the Translational Studies. 
7.
References
1.
Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of 
JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients 
with advanced solid tumors. J Clin Oncol 2015; 33(30): 3372-4.
2.
Siefker-Radtke AO, Mellado B, Decaestecker K, et al.  Ongoing phase 2 study of 
JNJ-42756493 (erdafitinib) (JNJ-42756403), a pan-fibroblast growth factor receptor 
(FGFR) tyrosine kinase inhibitor in patients (pts) with metastatic or unresectable 
urothelial carcinoma and FGFR gene alterations [abstract]. In: Proc ESMO 2016; 
Ann Oncol 2016 (suppl 6) abstract 845TiP

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Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K2: JNJ-42756493 (erdafitinib), FGFR Mutations or 
Fusions
Appendix I
Patient Pill Calendar
Storage: Store intact bottles at controlled room temperature 15°C to 30°C (59 to 86°F).
Pill Calendar Directions
1. Take your scheduled dose of each tablet.
2. If you forget, the missed tablets can be taken up to 6 hours after the scheduled time.
If it has been more than 6 hours since the missed dose, that dose will be skipped 
and you will resume treatment at the next scheduled time.
3. Please bring the empty bottle or any leftover tablets and your pill calendar to your 
next clinic visit.
4. Tablets must be swallowed whole with 8 ounces of water. Do not crush or chew.
5. Subjects should avoid consuming grapefruit or Seville oranges while on study 
treatment.
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Patient Pill Calendar
This is a calendar on which you are to record the time and number of tablets you take 
each day. You should take your scheduled dose of each tablet. Note the times and the 
number of tablets that you take each day. If you develop any side effects, please 
record them and anything you would like to tell the doctor in the space provided.  Bring 
any unused tablets and your completed pill calendar to your doctor’s visits.
JNJ-42756493 (erdafitinib) dose
Use tablet strengths
3 mg
1 x 3 mg
4 mg
1 x 4 mg
5 mg
1 x 5 mg
6 mg
2 x 3 mg
8 mg
2 x 4 mg
9 mg
3 x 3 mg
JNJ-42756493 (erdafitinib)
DAY 
Date
Time 
tablets
taken
Number of tablets taken
Use the space below to make 
notes about things you would like 
to tell the doctor (including unusual 
symptoms you experience, other 
medicine you have taken and 
anything else you think would be of 
interest.)
Month
Day
Year
3 mg
4 mg
5 mg
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20

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DAY 
Date
Time 
tablets
taken
Number of tablets taken
Use the space below to make 
notes about things you would like 
to tell the doctor (including unusual 
symptoms you experience, other 
medicine you have taken and 
anything else you think would be of 
interest.)
Month
Day
Year
3 mg
4 mg
5 mg
21
22
23
24
25
26
27
28

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Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K2: JNJ-42756493 (erdafitinib), FGFR Mutations or 
Fusions
Appendix II
Actionable Mutations for Sub-Protocol EAY131-K2
Other FGFR Fusion events or novel FGFR activating mutations not listed in the below table but 
identified by one of the designated outside laboratories as described in the MATCH Master 
Protocol will also be considered actionable mutations (aMOIs) at Level of Evidence Code 3.
Please refer to Section 1.4.2 of the MATCH Master Protocol for more information.
Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR1
COSM19176
SNV
p.N546K
3
FGFR1
COSM4771556
SNV
p.K656M
3
FGFR1
COSM35673
SNV
p.K656E
3
FGFR2
COSM29836 
SNV
p.A648T
3
FGFR2
COSM36906
SNV
p.C382R
3
FGFR2
COSM1346276
SNV
p.G305R
3
FGFR2
COSM36909
SNV
p.K660E
3
FGFR2
COSM683054
SNV
p.K659N
3
FGFR2
COSM250083
SNV
p.N550H
3
FGFR2
COSM36902
SNV
p.N550K
3
FGFR2
COSM36912
SNV
p.N550K
3
FGFR2
COSM49170
SNV
p.P253R
2
FGFR2
COSM36903
SNV
p.S252W
3
FGFR2
COSM36904
SNV
p.Y376C
3
FGFR3
COSM721
SNV
p.A393E
3
FGFR3
COSM716
SNV
p.G372C
3
FGFR3
COSM24842
SNV
p.G382R
3
FGFR3
COSM24802
SNV
p.G699C
3
FGFR3
COSM719
SNV
p.K652E
3
FGFR3
COSM720
SNV
p.K652M
3
FGFR3
COSM726
SNV
p.K652Q
3
FGFR3
COSM731
SNV
p.K652T
3
FGFR3
COSM714
SNV
p.R248C
3
FGFR3
COSM715
SNV
p.S249C
2
FGFR3
COSM17461
SNV
p.S373C
3
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Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR3
COSM718
SNV
p.Y375C
3
FGFR1
COSM48380 
SNV
p.T141R
2
FGFR2
COSM4994845 
SNV
p.S252L
2
FGFR2
COSM250081 
SNV
p.V395D
2
FGFR2
COSM36913
SNV
p.I547V
2
FGFR2
COSM4604460 
SNV
p.N549D
2
FGFR2
COSM3665555
SNV
p.N549S
2
FGFR3
COSM296687
SNV
p.R399C
2
FGFR3
COSM29438 
SNV
p.D641N
2
FGFR3
COSM732992
SNV
p.K715M
2
FGFR1
BAG4-FGFR1.B1F8
Fusion
BAG4-FGFR1.B1F8
3
FGFR1
BAG4-FGFR1.B2F6
Fusion
BAG4-FGFR1.B2F6
3
FGFR1
BCR-FGFR1.B4F10
Fusion
BCR-FGFR1.B4F10
3
FGFR1
CNTRL-FGFR1.C40F10
Fusion
CNTRL-FGFR1.C40F10
3
FGFR1
CPSF6-FGFR1.C8int8F10
Fusion
CPSF6-FGFR1.C8int8F10
3
FGFR2
CTNNB1-FGFR2.C1F10
Fusion
CTNNB1-FGFR2.C1F10
3
FGFR1
CUX1-FGFR1.C11F10
Fusion
CUX1-FGFR1.C11F10
3
FGFR1
ERLIN2-FGFR1.E8F2
Fusion
ERLIN2-FGFR1.E8F2
3
FGFR1
ERVK3_1-FGFR1.E3F10
Fusion
ERVK3_1-FGFR1.E3F10
3
FGFR1
FGFR1-ADAM32.F17A14
Fusion
FGFR1-ADAM32.F17A14
3
FGFR1
FGFR1-NTM.F1N2
Fusion
FGFR1-NTM.F1N2
3
FGFR1
FGFR1-
PLAG1.F1P2.COSF1108
Fusion
FGFR1-
PLAG1.F1P2.COSF1108
3
FGFR1
FGFR1-
PLAG1.F1P3.COSF1110
Fusion
FGFR1-
PLAG1.F1P3.COSF1110
3
FGFR1
FGFR1-
PLAG1.F2P2.COSF1111
Fusion
FGFR1-
PLAG1.F2P2.COSF1111
3
FGFR1
FGFR1-
PLAG1.F2P3.COSF1113
Fusion
FGFR1-
PLAG1.F2P3.COSF1113
3
FGFR1
FGFR1-
TACC1.F17T7.COSF1362
Fusion
FGFR1-
TACC1.F17T7.COSF1362
3
FGFR1
FGFR1-TACC1.F18T7
Fusion
FGFR1-TACC1.F18T7
2a
FGFR1
FN1-FGFR1.F22F3
Fusion
FN1-FGFR1.F22F3
3
FGFR1
FN1-FGFR1.F22F4
Fusion
FN1-FGFR1.F22F4
3
FGFR1
FN1-FGFR1.F23F3
Fusion
FN1-FGFR1.F23F3
3
FGFR1
FN1-FGFR1.F23F4
Fusion
FN1-FGFR1.F23F4
3

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Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR1
FN1-FGFR1.F28F5
Fusion
FN1-FGFR1.F28F5
3
FGFR1
FGFR1-
ZNF703.F14Z2.COSF720
Fusion
FGFR1-
ZNF703.F14Z2.COSF720
3
FGFR1
FGFR1OP-FGFR1.F5F10
Fusion
FGFR1OP-FGFR1.F5F10
3
FGFR1
FGFR1OP-FGFR1.F6F10
Fusion
FGFR1OP-FGFR1.F6F10
3
FGFR1
FGFR1OP-FGFR1.F7F10
Fusion
FGFR1OP-FGFR1.F7F10
3
FGFR1
FGFR1OP2-FGFR1.F4F10
Fusion
FGFR1OP2-FGFR1.F4F10
3
FGFR1
LRRFIP1-FGFR1.L8F10
Fusion
LRRFIP1-FGFR1.L8F10
3
FGFR1
MYO18A-FGFR1.M33F10
Fusion
MYO18A-FGFR1.M33F10
3
FGFR1
RANBP2-FGFR1.R20F10int9
Fusion
RANBP2-FGFR1.R20F10int9
3
FGFR1
SQSTM1-FGFR1.S6F10
Fusion
SQSTM1-FGFR1.S6F10
3
FGFR1
TPR-FGFR1.T22F10
Fusion
TPR-FGFR1.T22F10
3
FGFR1
TRIM24-FGFR1.T11F10
Fusion
TRIM24-FGFR1.T11F10
3
FGFR1
WHSC1L1-FGFR1.W14F5
Fusion
WHSC1L1-FGFR1.W14F5
3
FGFR1
WHSC1L1-FGFR1.W1F2
Fusion
WHSC1L1-FGFR1.W1F2
3
FGFR1
ZMYM2-FGFR1.Z17F10
Fusion
ZMYM2-FGFR1.Z17F10
3
FGFR2
CD44-FGFR2.C1F3
Fusion
CD44-FGFR2.C1F3
3
FGFR2
FGFR2-AFF3.F17A8
Fusion
FGFR2-AFF3.F17A8
3
FGFR2
FGFR2-AHCYL1.F17A2
Fusion
FGFR2-AHCYL1.F17A2
3
FGFR2
FGFR2-BICC1.F17B18
Fusion
FGFR2-BICC1.F17B18
3
FGFR2
FGFR2-BICC1.F17B2
Fusion
FGFR2-BICC1.F17B2
3
FGFR2
FGFR2-BICC1.F17B3.1
Fusion
FGFR2-BICC1.F17B3.1
3
FGFR2
FGFR2-CASP7.F17C2
Fusion
FGFR2-CASP7.F17C2
3
FGFR2
FGFR2-CCAR2.F17C4
Fusion
FGFR2-
KIAA1967_CCAR2.F17C4
3
FGFR2
FGFR2-CCDC6.F17C1
Fusion
FGFR2-CCDC6.F17C1
3
FGFR2
FGFR2-CCDC6.F17C2
Fusion
FGFR2-CCDC6.F17C2
3
FGFR2
FGFR2-CIT.F17C23
Fusion
FGFR2-CIT.F17C23
3
FGFR2
FGFR2-COL14A1.F17C34
Fusion
FGFR2-COL14A1.F17C34
3
FGFR2
FGFR2-CREB5.F17C8
Fusion
FGFR2-CREB5.F17C8
3
FGFR2
FGFR2-FAM76A.F17F2
Fusion
FGFR2-FAM76A.F17F2
3
FGFR2
FGFR2-KCTD1.F17K2
Fusion
FGFR2-KCTD1.F17K2
3
FGFR2
FGFR2-MGEA5.F17M12
Fusion
FGFR2-MGEA5.F17M12
3
FGFR2
FGFR2-NOL4.F17N7
Fusion
FGFR2-NOL4.F17N7
3

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Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR2
FGFR2-OFD1.F17O3
Fusion
FGFR2-OFD1.F17O3
3
FGFR2
FGFR2-PPHLN1.F17P3
Fusion
FGFR2-PPHLN1.F17P3
3
FGFR2
FGFR2-SHTN1.F17S7
Fusion
FGFR2-SHTN1.F17S7
3
FGFR2
FGFR2-TACC3.F17T11
Fusion
FGFR2-TACC3.F17T11
3
FGFR2
FGFR2-TXLNA.F17T6
Fusion
FGFR2-TXLNA.F17T6
3
FGFR2
FGFR2-USP10.F17del11U5
Fusion
FGFR2-USP10.F17del11U5
3
FGFR2
PARK2-FGFR2.P9F11
Fusion
PARK2-FGFR2.P9F11
3
FGFR2
PDHX-FGFR2.P1F7
Fusion
PDHX-FGFR2.P1F7
3
FGFR2
SLC45A3-FGFR2.S1F1
Fusion
SLC45A3-FGFR2.S1F1
3
FGFR2
SLC45A3-FGFR2.S1F2
Fusion
SLC45A3-FGFR2.S1F2
3
FGFR2
SNX19-FGFR2.S7F7
Fusion
SNX19-FGFR2.S7F7
3
FGFR3
SNX19-FGFR2.S8F7
Fusion
SNX19-FGFR2.S8F7
3
FGFR3
ETV6-FGFR3.E5F9
Fusion
ETV6-FGFR3.E5F9
3
FGFR3
FGFR3-AES.F17A2
Fusion
FGFR3-AES.F17A2
3
FGFR3
FGFR3-
BAIAP2L1.F17B2.COSF1346
Fusion
FGFR3-
BAIAP2L1.F17B2.COSF1346
3
FGFR3
FGFR3-ELAVL3.F17E2
Fusion
FGFR3-ELAVL3.F17E2
3
FGFR3
FGFR3-FBXO28.F17F4
Fusion
FGFR3-FBXO28.F17F4
3
FGFR3
FGFR3-JAKMIP1.F17J4
Fusion
FGFR3-JAKMIP1.F17J4
3
FGFR3
FGFR3-TACC3.F14T11
Fusion
FGFR3-TACC3.F14T11
3
FGFR3
FGFR3-TACC3.F15T11
Fusion
FGFR3-TACC3.F15T11
3
FGFR3
FGFR3-
TACC3.F16T10.COSF1359
Fusion
FGFR3-
TACC3.F16T10.COSF1359
3
FGFR3
FGFR3-
TACC3.F17T11.COSF1348
Fusion
FGFR3-
TACC3.F17T11.COSF1348
3
FGFR3
FGFR3-
TACC3.F17Intron17T9
Fusion
FGFR3-TACC3.F17Intron17T9
3
FGFR3
FGFR3-TACC3.F17T11.1
Fusion
FGFR3-TACC3.F17T11.1
3
FGFR3
FGFR3-TACC3.F17T11.2
Fusion
FGFR3-TACC3.F17T11.2
3
FGFR3
FGFR3-TACC3.F17ins1T10
Fusion
FGFR3-TACC3.F17ins1T10
2a
FGFR3
FGFR3-
TACC3.F17intron17T4
Fusion
FGFR3-TACC3.F17intron17T4
3
FGFR3
FGFR3-TACC3.F17T10
Fusion
FGFR3-TACC3.F17T10
3
FGFR3
FGFR3-
TACC3.F17T10.COSF1434
Fusion
FGFR3-
TACC3.F17T10.COSF1434
3
FGFR3
FGFR3-TACC3.F17T13.NGS
Fusion
FGFR3-TACC3.F17T13.NGS
3

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Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR3
FGFR3-TACC3.F17T14
Fusion
FGFR3-TACC3.F17T14
2a
FGFR3
FGFR3-TACC3.F17T14.1
Fusion
FGFR3-TACC3.F17T14.1
2a
FGFR3
FGFR3-TACC3.F17T4
Fusion
FGFR3-TACC3.F17T4
2a
FGFR3
FGFR3-TACC3.F17T5
Fusion
FGFR3-TACC3.F17T5
3
FGFR3
FGFR3-TACC3.F17T6
Fusion
FGFR3-TACC3.F17T6
3
FGFR3
FGFR3-TACC3.F17T7 
Fusion
FGFR3-TACC3.F17T7 
3
FGFR3
FGFR3-TACC3.F18T1
Fusion
FGFR3-TACC3.F18T1
2a
FGFR3
FGFR3-TACC3.F18T10
Fusion
FGFR3-TACC3.F18T10
3
FGFR3
FGFR3-TACC3.F18T10.1
Fusion
FGFR3-TACC3.F18T10.1
3
FGFR3
FGFR3-TACC3.F18T11
Fusion
FGFR3-TACC3.F18T11
3
FGFR3
FGFR3-TACC3.F18T11del5
Fusion
FGFR3-TACC3.F18T11del5
2a
FGFR3
FGFR3-TACC3.F18T4and5
Fusion
FGFR3-TACC3.F18T4and5
3
FGFR3
FGFR3-TACC3.F18T7.NGS
Fusion
FGFR3-TACC3.F18T7.NGS
3
FGFR3
FGFR3-
TACC3.TruncatedF17T4
Fusion
FGFR3-
TACC3.TruncatedF17T4
3
FGFR3
FGFR3-TACC3.F17T9
Fusion
FGFR3-TACC3.F17T9
3
FGFR3
FGFR3-TACC3.F17T8
Fusion
FGFR3-TACC3.F17T8
3
FGFR2
MVAR149
SNV
p.E565A
3
FGFR2
FGFR2-PPFIA2.F17P8
Fusion
FGFR2-PPFIA2.F17P8
3
FGFR2
FGFR2-SHTN1.F17S7
Fusion
FGFR2-SHTN1.F17S7
3
FGFR2
FGFR2-SMN2.F17S2
Fusion
FGFR2-SMN2.F17S2
3
FGFR2
FGFR2-TDRD1.F17T2
Fusion
FGFR2-TDRD1.F17T2
3
FGFR2
FGFR2-ATE1.F17A11
Fusion
FGFR2-ATE1.F17A11
3
FGFR2
FGFR2-ACOT11.F17A2
Fusion
FGFR2-ACOT11.F17A2
3
FGFR2
FGFR2-FOXP1.F17F3
Fusion
FGFR2-FOXP1.F17F3
3
FGFR2
FGFR2-TACC2.F17T17
Fusion
FGFR2-TACC2.F17T17
3
FGFR2
FGFR2-WAC.F17W5
Fusion
FGFR2-WAC.F17W5
3
FGFR2
FGFR2-BEND3.F17B5
Fusion
FGFR2-BEND3.F17B5
3
FGFR2
FGFR2-GLYR1.F17G6
Fusion
FGFR2-GLYR1.F17G6
3
FGFR2
FGFR2-CALCOCO1.F17C2
Fusion
FGFR2-CALCOCO1.F17C2
3
FGFR2
FGFR2-NRBF2.F17N2
Fusion
FGFR2-NRBF2.F17N2
3
FGFR2
FGFR2-CCDC6.F16C4
Fusion
FGFR2-CCDC6.F16C4
3
FGFR3
FGFR3-CLIP2.F18C9
Fusion
FGFR3-CLIP2.F18C9
3
FGFR3
FGFR3-OGDH.F18O3
Fusion
FGFR3-OGDH.F18O3
3

ECOG-ACRIN
EAY131-K2
Cancer Research Group
Version Date: August 19, 2020
50
Gene 
Name
Variant ID
Variant 
Type
Variant Description
Level of 
Evidence 
Code
FGFR3
FGFR3-TACC3.F18T8
Fusion
FGFR3-TACC3.F18T8
3
FGFR4
MVAR95
SNV
p.N535D
3

ECOG-ACRIN
EAY131-K2
Cancer Research Group
Version Date: August 19, 2020
51
Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K2: JNJ-42756493 (erdafitinib), FGFR Mutations or 
Fusions
Appendix III
Patient Drug Information Handout and Wallet Card
Information for Patients, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements 
Patient 
Name:
Diagnosis: 
Trial #:
Study 
Doctor:
Study 
Doctor 
Phone #:
Study 
Drug(s)
:
Erdafitinib 
(JNJ-
42756493)
Please show this paper to all your healthcare providers (doctors, physician assistants, nurse 
practitioners, pharmacists), and tell them you are taking part in a clinical trial sponsored by the 
National Cancer Institute. 
These are the things that your healthcare providers need to know:
Erdafitinib interacts with certain specific enzymes in your liver or other tissues like the gut and 
certain transport proteins that help move drugs in and out of cells.
Explanation
CYP 
isoenzymes
The enzymes in question are CYP3A4 and CYP2C9. 
Erdafitinib is broken down by these enzymes and may be affected by other drugs that 
are broken down by CYP3A4 and CYP2C9.  This could result in erdafitinib not being 
effective or causing toxicity.
Erdafitinib may affect drugs broken down by CYP3A4 or CYP2C9 enzymes.  However, 
it is unlikely this will affect how the drug works in the body (no clinically significant 
effects).
Protein 
transporters
The protein in question is P-glycoprotein (P-gp).  Erdafitinib is moved in and out of 
cells/organs by this transport protein. Administration of erdafitinib with other drugs 
moved by P-gp may increase their systemic exposure. Oral drugs with a narrow 
therapeutic index such as digoxin should be taken at least 6 hours before or after 
erdafitinib to minimize the potential for interactions.
Heart’s 
electrical 
activities
No clinically significant QT prolongation or cardiovascular effects have been noted to 
date.
These are the things that you need to know:
The study drug erdafitinib, may interact with other drugs which can cause side effects. For this 
reason, it is very important to tell your doctors about all your medicines, including: (a) medicines 
you are taking before this clinical trial, (b) medicines you start or stop taking during this study, (c) 
medicines you buy without a prescription (over-the-counter remedy), (d) herbals or supplements 
(e.g. St. John’s Wort). It is helpful to bring your medication bottles or an updated medication list 
with you.
Before you enroll onto the clinical trial, your study doctor will work with your regular health care 
Rev. Add16
Rev. Add25

ECOG-ACRIN
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Cancer Research Group
Version Date: August 19, 2020
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providers to review any medicines and herbal supplements that are considered strong 
inducers/inhibitors or substrates of CYP3A4, CYP2C9, or P-glycoprotein (P-gp).
x
Please be very careful!  Over-the-counter drugs (including herbal supplements) may 
contain ingredients that could interact with your study drug.  Speak to your doctors or 
pharmacist to determine if there could be any side effects. 
x
Make sure your doctor knows to avoid certain prescription medications. 
-
Digoxin
x
Your regular health care provider should check a frequently updated medical reference or 
call your study doctor before prescribing any new medicine or discontinuing any medicine.  
FEB/2019
(Next page: Patient Drug Interaction Wallet Card)