MATCH Treatment Subprotocol K1: Phase 2 Study of JNJ-42756493 (Erdafitinib) in Patients With Tumors With FGFR Amplifications
Phase: PHASE2
Conditions: Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
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
March 11, 2019
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 #19 to EAY131-K1, Phase 2 Study of JNJ-42756493 (Erdafitinib) in 
Patients with Tumors with FGFR Amplifications.
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permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 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.
This addendum is in response to Dr. S. Percy Ivy February 22, 2019 Request for Rapid 
Amendment for Erdafitnib (JNJ-42756493).
The following revisions to EAY131-K1 protocol have been made in this addendum:
Section
Change
1.
Cover Page
Updated Version Date.
2.
3.3
Updated the Erdafitnib CAEPR list with version 2.2, January 04, 2019.
The following revisions to EAY131-K1 Informed Consent Document have been made in this 
addendum:
Section
Change
1.
Page 1
Updated Version Date.
2.
What possible risks can 
I expect from taking 
part in this study?
Updated the possible risks language and the Erdafitnib risk list with 
version 2.2 January 04, 2019.
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-K1 so ECOG-ACRIN may 
activate it promptly.  

ii
Thank you.
Sincerely,
Pamela Cogliano
Senior Director, Protocol Development
Enclosure
CC:
Alain Mita, MD 
Ingrid Mayer.MD 
Heather Cheng, MD, Ph.D 
Alice Chen, MD
Keith Thomas Flaherty, MD
Lyndsay N. Harris. MD
Peter O’Dwyer, MD
Mickey Williams, PhD
James V. Tricoli, PhD
Stanley Hamilton, MD
Lisa McShane, PhD 
Larry Rubinstein, PhD
Robert Gray, PhD
Shuli Li, PhD
Lalitha Shankar, MD
Susanna Lee, MD, PhD
Constantine Gastonis, PhD
Paolo Caimi, MD
Shaji Kumar, MD
Carlos Arteaga, MD
Edith Mitchell, MD
John J. Wright, MD, PhD
Bruce Giantonio, MD
Donna Marinucci
Kerry Higgins
Gayle Ipock
Jean MacDonald
Carol Chami, R.N.
Juanita Andrews
Melinda Flood
Julianne Human
Kelly Redmond
Becky Fillingham
Jeffrey Zhang
Amy Li
Kevin Pollard
Abuchi Agu
Michael T. Balco
Lauren Lambert
Cayden Maican
Margaret Cavenagh
Ben Kim
Alexandra Sachs
Russell McDaniel

EAY131-K1
1
Molecular Analysis for Therapy 
Choice (MATCH)
MATCH Treatment Subprotocol K1: Phase 2 Study of 
JNJ-42756493 (Erdafitinib) in Patients with Tumors with 
FGFR Amplifications
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: March 11, 2019
NOTE: This subprotocol (EAY131-K1) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131).
SUBPROTOCOL ACTIVATION DATE
Incorporated in Addendum #13
Addendum #16
Addendum #19
Agent
IND#
NSC#
Supply
JNJ-42756493 (Erdafitinib)
IND Sponsor: DCTD, NCI IND#:
781558
NCI Supplied

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Table of Contents
Molecular Analysis for Therapy Choice (MATCH) ...................................................... i 
MATCH Treatment Subprotocol K1: Phase 2 Study of JNJ-42756493 (Erdafitinib) in 
Patients with Tumors with FGFR Amplifications................................................. 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 ......................................................................................... 12 
2.1 Eligibility Criteria ..................................................................................... 12 
3. JNJ-42756493 (Erdafitinib) Treatment Plan ...................................................... 15 
3.1 Administration Schedule ......................................................................... 15 
3.2 Adverse Event Reporting Requirements ................................................. 16 
3.3 Comprehensive Adverse Events and Potential Risks List (CAEPR) for JNJ-
42756493 (Erdafitinib, NSC 781558) ....................................................... 19 
3.4 Dose Modifications ................................................................................. 23 
3.5 Supportive Care ....................................................................................... 33 
3.6 Duration of Agent-specific treatment ..................................................... 33 
3.7 Duration of Follow-Up ............................................................................. 34 
4. Study Parameters .............................................................................................. 35 
4.1 Therapeutic Parameters for JNJ-42756493 (Erdafitinib) Treatment ...... 35 
5. Drug Formulation and Procurement ................................................................. 38 
5.1 JNJ-42756493 (NSC 781558) ................................................................... 39 
6. Translational Studies ......................................................................................... 42 
7. References ........................................................................................................ 42 
Appendix I  Patient Pill Calendar ............................................................................. 43 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-K1 ............................ 46 
Appendix III  Patient Drug Information Handout and Wallet Card ......................... 47 
 

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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@vanderbilt.edu
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 9 mg as per protocol 
guidance
Until Progression 
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 bound to 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.
A poster at ESMO2016 presented data in urothelial carcinoma (UC) 
patients from the same Phase 1 study. Thirty pts with UC were treated 
at 2 mg QD (n=1), 9 mg QD (n=12), 10 mg ID (n=15), 12 mg QD 
(n=1), or 12 mg ID (n=1). Across these dose levels, median treatment 
duration was 3.3 months (mo). The most common drug-related AEs 
were hyperphosphatemia (53%), dry mouth (47%), diarrhea (43%), 
and dry skin (43%); all of these were grade 1 or 2 severity, except for 
1 case of grade 3 hyperphosphatemia (3%) and 2 cases of grade 3 
diarrhea (7%). The most common grade ≥3 AEs were anemia (17%), 
hand-foot syndrome (13%), and stomatitis (11%). Among FGFR-
mutated or translocated, response evaluable UC pts (as of 06 Jun 
2016), 7/11(63.6%) pts were treated at 9 mg QD and achieved PR 
with median duration of response of 7.2 mo (95% CI 3.8, 15.3), and 
4/13 (30.8%) pts were treated at 10 mg ID and achieved PR.
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. The RP2D was chosen to be 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.
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 

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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 
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 

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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 
potential for clinical activity.

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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
Eligibility Criteria
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 Amplification as determined via the 
MATCH Master Protocol and 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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JNJ-42756493 (erdafitinib) should be administered daily at approximately the 
same time, and the interval between two consecutive doses should be 
approximately 24 hours. Missed doses for any reason (including vomiting 
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 K1
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 K1 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 subject is on JNJ-
42756493 (erdafitinib), or within 28 days of the subject’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 

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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 
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 ALT t 3 x
ULN and INR > 1.5 and no alkaline phosphatase [ALP] 
elevation).
EAY131 – Subprotocol K1 specific expedited reporting 
exceptions:
For Subprotocol K1, 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.

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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-
cancer treatment (including the treatment on this protocol). 
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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1This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all 
Principal Investigators at the time of revision. The current version can be obtained by contacting 
PIO@CTEP.NCI.NIH.GOV. Your name, the name of the investigator, the protocol and the agent should 
be included in the e-mail.
2Central serous retinopathy includes: chorioretinopathy, retinal detachment, retinal oedema, detachment 
of retinal pigment epithelium, detachment of macular retinal pigment epithelium, retinopathy and vitreous 
detachment.
3Eye disorders includes, but is not limited to eye disorder with redness and irritation of the eye, maybe 
associated with increased tearing of the eyes, itchy eyes, and inflamed eyes.
4Nail disorder includes, but is not limited to, onycholysis, onychalgia, onychoclasis, nail dystrophy, nail 
loss, nail bed bleeding, nail bed inflammation, nail discomfort, nail discoloration, and nail ridging.
Adverse events reported on Erdafitinib (JNJ-42756493) trials, but for which there is 
insufficient evidence to suggest that there was a reasonable possibility that Erdafitinib 
(JNJ-42756493) caused the adverse event:
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

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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 
agent.

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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 

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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 medical monitor 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 medical monitor 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
Guidelines for the clinical management of elevated serum phosphate levels are 
presented in Table 3.

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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 medical monitor 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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Table 3:
Guidelines for Management of Serum Phosphate Elevation
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 medical monitor 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 medical monitor 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)
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.
Sorbitol lozenges 
PRN and Cevimeline 
30 mg TID or 
Pilocarpine 5 mg TID

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Table 4:
Guidelines for the Management of Dry Mouth (Xerostomia)
Grade and Definition
Study Drug 
Management
Medical 
Management 
When resolved to 
≤Grade 1 or baseline, 
restart at 1 dose level 
below in consultation with 
the medical monitor.
Grade 4: life-threatening 
consequences, urgent 
intervention indicated
Discontinue study drug.  
Evaluation and 
therapy as clinically 
indicated
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 medical monitor.
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 
medical monitor.
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.  

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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%).
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 medical monitor.
Use topical steroid ointment or 
cream* BID and zinc oxide 13-
40% at night for areas with 
fissures.
Grade 4: Dry skin with life-
threatening 
consequences, urgent 
intervention indicated
Discontinue study drug.  
Evaluation and therapy as 
clinically indicated
* Topical Steroid Ointments: Clobetasol 0.05%, Betamethasone 0.05%, Fluocinonide 0.05%
Guidelines for Management of Nail Toxicity (Onycholysis, Onychodystrophy, and 
Paronychia)
Guidelines for management of nail discoloration/loss/ridging 
(onycholysis/onychodystrophy) are provided in Table 7. Guidelines for the 
management of paronychia are provided in Table 8.
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

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x
Nail polish and imitation fingernails should not be worn until the nails have 
grown out and returned to normal
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 medical 
monitor.
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 
medical monitor.
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
a Vinegar soaks consist of soaking fingers or toes in a solution of white vinegar in water 1:1 for 
15 minutes every day. Examples of topical antibiotic ointments: Mupirocin 2%, gentamycin, 
bacitracin zinc/polymixin B

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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 medical 
monitor
Topical antibiotics AND vinegar soaksa
AND topical antifungal lacquer daily for 6+ 
weeks (ciclopirox olamine 8% OR 
efinaconazole 10% OR amorolfine 5% 
weekly OR bifonazole/urea ointment daily)
For signs of infection (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 
medical monitor.
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 
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

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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 medical monitor.a
Monitor for recurrence every 1 to 2 weeks for a month 
and as clinically appropriate thereafter. If there is no 
recurrence then re-escalation can be considered in 
consultation with the medical monitor.a
Refer the subject for an 
ophthalmologic examination.
For retinal pathology 
perform OCT as appropriate 
and consider referral to a 
retinal specialist for further 
evaluation. 
Follow specific treatment per 
the ophthalmologist’s 
recommendation. 
Grade 2: Moderate; 
minimal, local
or noninvasive intervention 
indicated; limiting age 
appropriate instrumental 
ADL
Grade 3: Severe or 
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 medical monitor.
If the toxicity is Grade 3, report as a serious adverse 
Refer subject to an 
ophthalmologist for 
evaluation with an 
ophthalmologic examination.
For retinal pathology, 
perform OCT as appropriate 
and consider referral to a 
retinal specialist for further 
evaluation. 
Follow specific treatment per 
the ophthalmologist’s 
recommendation. 

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Table 9:
Guidelines for Management of Eye Toxicity
Grade and Definition
Study Drug Management
Medical Management
medically significant but not 
immediate sight-
threatening; hospitalization 
or prolongation of existing 
hospitalization indicated; 
disabling; limiting self-care 
ADL
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 medical monitor 
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.
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 medical monitor 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 medical monitor 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.
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.

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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.
C.
Blood pregnancy test (women of childbearing potential) required prior to beginning treatment.
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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 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.

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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 K1, 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 
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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).
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
JNJ-42756493 (NSC 781558)
5.1.1
Other Names:
Erdafitinib
5.1.2
Classification:
pan-FGFR tyrosine kinase inhibitor
5.1.3
Mode of Action:
JNJ-42756493 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 
JNJ42756493 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
JNJ-42756493 (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

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5.1.6
How Supplied:
Janssen Pharmaceuticals supplies and CTEP, NCI, DCTD distributes 
JNJ-42756493.  The agent is available as 3 mg (yellow), 4 mg 
(orange), 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
JNJ42756493 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:
JNJ-42756493 shows weak inhibition potential towards CYP1A2, 
CYP2C9, CYP2C19, CYP2D6, and CYP3A4. No clinical studies have 
been conducted yet for JNJ-42756493 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 JNJ-42756493. 
With CYP2D6 and CYP2C8 can potentially be involved to a minor 
extent. Caution is to be exercised in combining JNJ-42756493 with 
strong inhibitors/inducers of CYP3A4/5 and CYP2C9. Subjects should 
be closely monitored for potential toxicities, and appropriate action, 
including temporary interruption of JNJ-42756493, as appropriate 
should be taken.
JNJ-42756493 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

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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 
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.

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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 
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 K1: JNJ-42756493 (Erdafitinib), FGFR Amplifications
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. Tablets should be taken at least 1 hour before eating or 2 hours after a meal, at 
approximately the same time each day.
6. 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 
3 mg
4 mg
5 mg
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
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23

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DAY 
Date
Time tablets
taken
Number of tablets 
taken 
3 mg
4 mg
5 mg
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
24
25
26
27
28
Patient Signature: __________________________________ Date: _____________

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Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K1: JNJ-42756493 (Erdafitinib), FGFR Amplifications
Appendix II
Actionable Mutations for Sub-Protocol EAY131-K1
Gene Name
Variant ID
Variant Type
Variant Description
Level of 
Evidence Code
FGFR1
FGFR1
CNV
Amplification
3
FGFR2
FGFR2
CNV
Amplification
3
FGFR3
FGFR3
CNV
Amplification
3
FGFR4
FGFR4
CNV
Amplification
3

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Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol K1: JNJ-42756493 (Erdafitinib), FGFR Amplifications
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 
The patient ____________________________ is enrolled on a clinical trial using the 
experimental study drug, JNJ42756493 (erdafitinib). This clinical trial is sponsored by
the National Cancer Institute.  This form is addressed to the patient, but includes 
important information for others who care for this patient. 
These are the things that you as a healthcare provider need to know:
JNJ42756493 interacts with a certain specific enzyme in your liver, and a certain 
transport protein that helps move drugs in and out of cells.  JNJ42756493 may interact 
with the heart’s electrical activity (QTc prolongation).
x
The enzymes in question are CYP3A4 and CYP2C9. JNJ42756493 is broken down 
by these enzymes and may be affected by other drugs that inhibit or induce them.
x
CYP3A4 and CYP2C9 can be considered the dominant CYP450 enzymes involved 
in the microsomal metabolism of JNJ-42756493. Caution is to be exercised in 
combining JNJ-42756493 with inhibitors/inducers of CYP3A4 and CYP2C9. JNJ-
42756493 may be affected by drugs that increase or inhibit metabolism of CYP450 
3A4 substrates. Therefore, administering JNJ-42756493 with drugs that potently 
inhibit or induce CYP450 3A4/5 or 2C9 has the potential to change the drug 
therapeutic effects (inducers) and toxicity (inhibitors).
x
The protein in question is P-glycoprotein. JNJ-42756493 is moved in and out of 
cells/organs by this transport protein. Potent inhibitors of P-glycoprotein should be 
contraindicated.
x
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. Therefore, concomitant administration of medications that induce 
QTc should be used with caution.
To the patient: Take this paper with you to your medical appointments and keep 
the attached information card in your wallet.  
JNJ-42756493 may interact with other drugs which can cause side effects. For this 
reason, it is very important to tell your study doctors of any medicines you are taking 
before you enroll onto this clinical trial.  It is also very important to tell your doctors if you 
stop taking any regular medicines, or if you start taking a new medicine while you take 
part in this study.  When you talk about your current medications with your doctors,
include medicine you buy without a prescription (over-the-counter remedy), or any herbal 
supplements such as St. John’s Wort. It is helpful to bring your medication bottles or an 
updated medication list with you.
Many health care providers can write prescriptions.  You must tell all of your health care 
providers (doctors, physician assistants, nurse practitioners, pharmacists) you are taking 
part in a clinical trial. 
Rev. Add16

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These are the things that you and they need to know: 
JNJ-42756493 must be used very carefully with other medicines that use certain liver 
enzymes or transport proteins to be effective or to be cleared from your system.
Before you enroll onto the clinical trial, your study doctor will work with your regular 
health care providers to review any medicines and herbal supplements that are 
considered strong inducers/inhibitors of CYP3A4, CYP2C9 or P-glycoprotein.  
Concomitant administration of medications that induce QTc should be used with 
caution.
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
Avoid consuming grapefruit or Seville oranges while taking JNJ-42756493
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.  Your study doctor’s name is 
_____________________________________ and he or she can be contacted at 
_____________________________________
STUDY DRUG INFORMATION WALLET CARD  
You are enrolled on a clinical trial using the experimental 
study drug JNJ-42756493. This clinical trial is sponsored 
by the NCI.  JNJ-42756493 (erdafitinib) may interact with 
drugs that are processed by your liver, or use certain 
transport proteins in your body, or affects the 
electrical activity of your heart.  Because of this, it is 
very important to:
¾ Tell your doctors if you stop taking any medicines or if 
you start taking any new medicines.
¾ Tell all of your health care providers (doctors, physician 
assistants, nurse practitioners, or pharmacists) that you 
are taking part in a clinical trial.
¾ Check with your doctor or pharmacist whenever you 
need to use an over-the-counter medicine or herbal 
supplement.
JNJ-42756493 interacts with specific liver enzymes called 
CYP3A4 and CYP2C9 and transport protein P-
glycoprotein.  JNJ42756493 must be used very carefully 
with other medicines that interact with these enzymes or 
transporter.  Consistent QT prolongation was seen across 
species in nonclinical studies. Therefore, concomitant 
administration of medications that induce QTc should 
be used with caution.
¾ Before you enroll onto the clinical trial, your study 
doctor will work with your regular health care 
providers to review any medicines and herbal 
supplements that are considered strong 
inducers/inhibitors of CYP3A4, CYP2C9, or P-
glycoprotein.
¾ Avoid consuming grapefruit or Seville oranges while 
taking study drug 
¾ Before prescribing new medicines, your regular 
health care providers should go to a frequently-
updated medical reference for a list of drugs to 
avoid, or contact your study doctor.  
¾ Your study doctor’s name is 
_____________________________ and can be 
contacted at 
_________________________________.