Clinical trial NCT04439240
Conditions: Advanced Lymphoma Advanced Malignant Solid Neoplasm Hematopoietic and Lymphoid Cell Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Plasma Cell Myeloma
Keywords: FGFR AZD4547 NCI-MATCH
Sponsor: National Cancer Institute (NCI)
Start date: 2016-05-31; Completion date: 2020-06-30
Enrollment: 52 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II MATCH treatment trial identifies the effects of AZD4547 in patients whose cancer has genetic changes called FGFR gene alterations. AZD4547 may stop the growth of cancer cells by blocking FGFR proteins which may be needed for cell growth. Researchers hope to learn if AZD4547 will shrink this type of cancer or stop its growth.

Detailed description:
PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive FGFR inhibitor AZD4547 (AZD4547) orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Arms: arm 1: Patients receive AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: FGFR Inhibitor AZD4547
Intervention descriptions: intervention 1: Given PO

Protocol documents:
Prot_001.pdf: 
EAY131-W 
1 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol W: Phase II Study of 
AZD4547 in Patients with Tumors with Aberrations in the 
FGFR Pathway 
AZD4547 TREATMENT SUBPROTOCOL CHAIR: 
Young Kwang Chae, MD, MPH, MBA 
AZD4547 TREATMENT SUBPROTOCOL CO-
CHAIR: 
Christos Vaklavas, MD 
AZD4547 TRANSLATIONAL CHAIR: 
Heather Cheng, MD, PhD 
Version Date:  May 16, 2018 
NOTE: This subprotocol (EAY131-W) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131). 
SUBPROTOCOL ACTIVATION DATE 
May 31, 2016 (incorporated in Addendum #3) 
Addendum #4 – 7/16 
NOTE: As of 11/17, all protocol changes will 
be noted by addendum number. Please 
reference the activation memo for the 
addendum activation date. 
Addendum #5 – 12/16 
Addendum #7 – 3/17 
Addendum #13 
Agent
IND#
NSC#
Supply
AZD4547 
 
765338 
NCI Supplied 
Rev. Add13 


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Table of Contents 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 AZD4547 .................................................................................................... 5 
1.2 Supporting Preliminary Data ..................................................................... 7 
2. Selection of Patients ........................................................................................... 8 
2.1 Eligibility Criteria ....................................................................................... 8 
3. AZD4547 Treatment Plan .................................................................................. 10 
3.1 Administration Schedule ......................................................................... 10 
3.2 Adverse Event Reporting Requirements ................................................. 10 
3.3 Comprehensive Adverse Events and Potential Risks List (CAEPR) for 
AZD4547 (NSC 765338) ........................................................................... 13 
3.4 Dose Modifications ................................................................................. 16 
3.5 Supportive Care ....................................................................................... 21 
3.6 Duration of Agent-specific treatment ..................................................... 21 
3.7 Duration of Follow-Up ............................................................................. 21 
4. Study Parameters .............................................................................................. 22 
4.1 Therapeutic Parameters for AZD4547 Treatment .................................. 22 
5. Drug Formulation and Procurement ................................................................. 24 
5.1 AZD4547 (NSC 765338) ........................................................................... 25 
6. Translational Studies ......................................................................................... 27 
7. References ........................................................................................................ 27 
Appendix I  Patient Pill Calendar ............................................................................. 28 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-W............................. 30 
Appendix III  Patient Drug Information Handout and Wallet Card ......................... 33 
 


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TREATMENT SUBPROTOCOL CHAIR 
Young Kwang Chae, MD, MPH, MBA 
Assistant Professor 
Co-Director, Developmental Therapeutics 
Program of Division of Hematology Oncology 
Robert H. Lurie Comprehensive Cancer 
Center of Northwestern University 
645 N. Michigan Ave. Suite 1006. 
Chicago, IL 60611 
Tel: 312 626 4248 
Fax: 312 695 0370 
Email: young.chae@northwestern.edu 
 
TREATMENT SUBPROTOCOL CO-CHAIR  
Christos Vaklavas, M.D. 
Assistant Professor 
Division of Hematology/Oncology 
Department of Medicine 
UAB Comprehensive Cancer Center 
NP2540M 
1802 6th Avenue South 
Birmingham, AL 35294-3300 
Tel: 205 934 5677 
Fax: 205 975 3910 
Email: cvaklavas@uabmc.edu 
 
TRANSLATIONAL CHAIR 
Heather Cheng MD, PhD 
Assistant Professor 
Department of Medical Oncology 
University of Washington 
825 Eastlake Avenue East 
Seattle, WA 98109 
Tel: (206) 288-1406 
Fax: (206) 288-6681 
Email: hhcheng@u.washington.edu 
 
 
 
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Schema 
 
Long-Term Follow-Up
AZD4547, 80 mg PO BID 
Until progression 
Cycle = 28 days
Accrual Goal: 70
 
 
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1. Introduction 
1.1 
AZD4547 
Background: 
AZD4547 is a selective inhibitor of the fibroblast growth factor receptor (FGFR) 1-
3 kinases. It exhibits an in vitro IC50 of < 5nM for FGFR1-3 and has a 
significantly lower potency for inhibition of FGFR4 insulin-like growth factor 1 
receptor (IGFIR) and kinase insert domain receptor (KFR) (i.e. vascular 
endothelial growth factor receptor) [VEGFR]. AZD4547 has demonstrated potent 
anti-tumor effects in several human cancer cell lines dependent on FGFR1-3 
including KMS11, KG1a, SNU16, RT112, NCI-H2077, NCI-H716 and SUM52PE 
and in xenograft models derived from these cell lines. 
AZD4547 has been evaluated in a phase I dose-escalation study which has 
recently completed accrual (NCT00979134). This study established the safety, 
PK and PD properties of the drug and a recommended monotherapy dose of 80 
mg twice daily. Dose-expansion cohorts, which were tied to FGFR1 or FGFR2 
amplification as a biomarker, demonstrated activity with a small number of 
responses in biomarker selected populations. AZD4547 has been evaluated in a 
Phase I SqNSCLC cohort and in a phase II study in advanced gastric cancer. 
AZD4547 is currently being evaluated in studies in the US and in Europe aimed 
at evaluating its efficacy in biomarker selected populations, principally subjects 
with FGFR1-3 amplifications, point mutations or fusions. 
Pharmacokinetics of AZD4547: 
Preliminary PK data are available from Studies D2610C00001 (single and 
multiple bid dosing of 20 mg to 200 mg AZD4547 oral suspension formulation 
and 120 mg to 200 mg AZD4547 tablet formulation) and D2610C00003 (a Phase 
I/IIa AZD4547 study in combination with exemestane or fulvestrant in estrogen 
receptor (ER+) breast cancer. Final reported data are available for D2610C00002 
(single and multiple bid dosing of 40 to 120 mg and qd dosing of 160 mg 
AZD4547 oral tablet formulation in Japanese patients) and D2610C00004 (an 
open label Phase IIa study in AZD4547 monotherapy versus paclitaxel in 
advanced gastric cancer). 
These studies showed that AZD4547 has a moderate rate of absorption, with a 
median time to maximum plasma concentration (tMax) of 1 to 4 hours. Following 
a single dose of AZD4547, peak plasma concentrations declined with a 
consistent terminal elimination half-life (t1/2) across the dose-levels; mean value 
approximately 30 hours. The oral clearance was approximately 50 L/h and the 
oral volume of distribution was greater than total body water indicating that 
AZD4547 was well-distributed in the tissues. 
Safety: 
In the dose-escalation study (Study D2610C00001), dose-limiting toxicities 
(DLTs) have been reported for 7 patients: raised liver function tests (80 mg bd 
[suspension]), mucositis (120 mg bd [tablet]), stomatitis (150 mg bd 
[suspension]), uncontrolled phosphate levels (160 mg bd [tablet]), renal failure 
(200 mg bd [suspension]), renal failure (160 mg bd [tablet]), and liver enzyme 
changes (200 mg bd [tablet]). The 160 mg bd dose was declared non-tolerated 
as 2/6 patients experienced DLTs. 
Rev. 7/16 
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Dose expansion cohorts included 94 subjects reporting AEs. The most commonly 
reported AEs (overall; all doses in all parts of the study [94 patients]) were 
constipation (43 [45.7%] patients); dry mouth (40 [42.6%] patients), stomatitis (39 
[41.5%] patients), diarrhea (33 [35.1%] patients), alopecia (32 [34.0%] patients), 
decreased appetite (31 [33.0%] patients), and vomiting (31 [33.0 %] patients). 
As of 04 June 2014, there have been 49 serious adverse events (SAEs) reported 
in 25 patients; this includes 1 SAE (respiratory distress) in 1 patient, which 
occurred after the 28-day follow-up period. Nineteen SAEs in 12 patients were 
considered by the reporting investigator to be related to treatment with AZD4547. 
Asthenia, blood creatinine increased, chorioretinopathy, dehydration, dyspnea, 
general physical health deterioration, renal failure, sepsis, and vomiting are SAE 
terms reported on more than one occasion. 
In the gastric cancer monotherapy vs. paclitaxel study (Study D2610C00004), 40 
subjects were enrolled. The most commonly reported AEs (of any grade) 
reported for patients receiving AZD4547 were: decreased appetite (16 [40.0%] 
patients), asthenia (11 [27.5%] patients), nausea (10 [25.0%] patients), 
constipation (10 [25.0%] patients), stomatitis (10 [25.0%] patients), abdominal 
pain (9 [22.5%] patients), abdominal pain upper (9 [22.5%] patients), dry mouth 
(9 [22.5%] patients), and vomiting (8 [20.0 %] patients). As of 05 August 2013, 12 
on-treatment or post-treatment SAEs had been reported for 8 patients receiving 
AZD4547. AEs leading to discontinuation of study treatment were reported for 5 
patients and 2 patients in the AZD4547 and paclitaxel groups, respectively. In the 
AZD4547 group these were: arterial disorder (1 patient; fatal; not considered by 
the reporting investigator to be related to treatment), blood bilirubin increased (1 
patient), intestinal hemorrhage (1 patient; fatal; not considered by the reporting 
investigator to be related to treatment), retinal pigment epithelial detachment 
(RPED; 1 patient), and RPED and bile duct obstruction (both terms in 1 patient). 
On the basis of these the studies, the following are considered AEs associated 
with AZD4547: Alopecia, blood creatinine increased, diarrhea, dysgeusia, 
epithelial and mucosal dryness (including palmar-plantar erythrodysesthesia 
syndrome), hair and eyelash disorders, hyperphosphatemia, nail disorders, 
retinal pigment epithelial detachment (RPED), stomatitis, and transaminases 
increased. 
More specifically the following adverse events are expected to occur at a 
frequency greater than 20%: retinal detachment (usually preceded by symptoms 
and with good prognosis), constipation, diarrhea, dry mouth, oral mucositis, 
vomiting, fatigue, and anorexia. In addition, ALT and/or AST elevations and 
hyperphosphatemia may occur with a frequency >20%. 
Less likely adverse events include xerophthalmia, keratitis, retinopathy, 
abdominal pain, nausea, altered taste, alopecia, dry skin, hand foot syndrome, 
nail discoloration and dystrophy. In addition, elevations in the ALP and serum 
creatinine, and decreases in the neutrophil count and ejection fraction may occur. 
Rarely QT prolongation may occur. Also, since AZD457 is a selective inhibitor of 
the fibroblast growth factor receptor and may alter bone maturation/metabolism, 
there is a theoretical risk that patients under 25 years of age may not reach their 
maximum height while taking AZD4547. This adverse event, however, has not 
been observed or reported as initial trials have not included patients younger 
than 25 years of age. 


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Efficacy: 
There are only sparse clinical data response to AZD4547 in FGFR amplified 
tumours as determined by FISH. This is based on two trials that did not meet this 
endpoint in ORR in the relevant histologies (ASCO 2014 abstract #8035 & 2620). 
Responses have been documented in patients treated with JNJ42756493 or 
Novartis FGFR inhibitors (2 of 5 patients treated with BJG398 (Personal 
communication, AstraZeneca, Oct 2014). Responses in tumors harboring FGFR2 
and FGFR3 fusions appear to be more robust than in tumors with FGFR gene 
amplifications based on early clinical data. 
1.2 
Supporting Preliminary Data  
While FGFR1-3 gene amplifications had been widely recognized prior to the 
initiation of clinical studies of AZD4547, multiple newer studies have also 
described FGFR gene point mutations and translocations across a diverse array 
of cancer types. Currently, there are preclinical data that tumors with FGFR2 and 
FGFR3 point mutations and FGFR3/TACC3 fusions are responsive to AZD4547; 
Responses in tumors harboring FGFR2 and FGFR3 fusions appear to be more 
robust than in tumors with FGFR gene amplifications based on early clinical data. 
Based on the TCGA dataset, the prevalence of FGFR point mutations is above 
10% in bladder cancer, uterine cancer, cholangiocarcinoma and melanoma and 
5-10% in lung adenocarcinoma, lung squamous cell carcinoma, gastric and 
pancreas cancer. Although the prevalence of FGFR fusions continues to be 
defined, fusions have been described in lung, head and neck and bladder cancer 
as well as GBM and cholangiocarcinoma. Moreover, clinical activity of FGFR 
inhibitors has been reported in patients whose cancers contain FGFR fusions. 
 
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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 1-3 mutation or translocation as determined 
by the MATCH screening assessment. See Appendix II for a list of the 
FGFR gene alterations 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 AZD4547 or 
compounds of similar chemical or biologic composition. 
2.1.5 
Patients must have an ECHO or a nuclear study (MUGA or First 
Pass) within 4 weeks prior to registration to treatment and must not 
have a left ventricular ejection fraction (LVEF) < institutional lower 
limit of normal (LLN). If the LLN is not defined at a site, the LVEF must 
be > 50% for the patient to be eligible. 
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Date of ECHO/nuclear study:  _______________ 
2.1.6 
Patients must have a pre-study eye exam by an ophthalmologist. See 
Section 3.4.2. Patients with current evidence of corneal or retinal 
disorder/keratopathy are excluded. 
2.1.7 
Patients must not have received prior FGFR specific inhibitors (e.g. 
BGJ398, erdafitinib, BAY1163877, LY2874455). Prior non-selective 
FGFR inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, 
brivanib, lucitanib, lenvatinib) will be allowed. 
2.1.8 
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. 
2.1.9 
Patients must not be currently using medications that can elevate 
serum phosphorous and/or calcium levels. 
2.1.9.1 
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. 
2.1.9.2 
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. 
 
 
 
 
 
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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3. 
AZD4547 Treatment Plan 
3.1 
Administration Schedule 
Patients who meet the eligibility criteria and provided a signed informed consent 
form will receive AZD4547 at 80 mg PO BID continuously. Dosing is irrespective 
of body weight. 
A cycle is defined as 28 days. 
Repeat cycles until progression or unacceptable toxicity. 
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 W 
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 W specific expedited reporting 
requirements: 
• 
Pregnancies:  Pregnancies and suspected pregnancies 
(including a positive or inconclusive pregnancy test, regardless 
of age or disease state) occurring while the subject is on 
AZD4547, or within 28 days of the subject’s last dose of 
AZD4547, 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. 
 


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EAY131 – Subprotocol W specific expedited reporting 
exceptions: 
For Subprotocol W, the adverse events listed below do not require 
expedited reporting via CTEP-AERS: 
• 
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 
• 
A second malignancy is a cancer that is UNRELATED to any 
prior anti-cancer treatment (including the treatment on this 
protocol).  Second malignancies require ONLY routine reporting 
as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days. 
2. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave confirming the diagnosis. 
3. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave. 
• 
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 


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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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3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for AZD4547 
(NSC 765338) 
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a 
single list of reported and/or potential adverse events (AE) associated with an 
agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Specific Protocol Exceptions to Expedited 
Reporting (SPEER), appears in a separate column and is identified with bold and 
italicized text. This subset of AEs (SPEER) is a list of events that are protocol 
specific exceptions to expedited reporting to NCI via CTEP-AERS (except as 
noted below). Refer to the 'CTEP, NCI Guidelines: Adverse Event Reporting 
Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguide
lines.pdf for further clarification. Frequency is provided based on 168 patients. 
Below is the CAEPR for AZD4547. 
NOTE: 
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 in the SPEER. 
Version 2.2, May 24, 20161 
 Adverse Events with Possible  
 Relationship to AZD4547 
 (CTCAE 4.0 Term) 
[n= 168] 
 
 Specific Protocol 
Exceptions to 
Expedited Reporting 
(SPEER)  
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)  
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
 
Anemia 
 
 Anemia (Gr 2) 
EYE DISORDERS 
  
 
Dry eye 
 
  
 
Keratitis 
 
  
Eye disorders - Other 
(retinal pigment epithelium 
detachment)2 
 
 
 Eye disorders - Other 
(retinal pigment 
epithelium detachment)2 
 
Retinopathy 
 
  
GASTROINTESTINAL DISORDERS 
  
 
Abdominal pain 
 
 Abdominal pain (Gr 2) 
Constipation 
 
 
 Constipation (Gr 2) 
Diarrhea 
 
 
 Diarrhea (Gr 2) 
Dry mouth 
 
 
 Dry mouth (Gr 2) 
Mucositis oral 
 
 
 Mucositis oral (Gr 2) 
 
Nausea 
 
  
Vomiting 
 
 
 Vomiting (Gr 2) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
Fatigue 
 
 
 Fatigue (Gr 2) 
INVESTIGATIONS 
  
Alanine aminotransferase 
increased 
 
 
 Alanine aminotransferase 
increased (Gr 2) 
 
Alkaline phosphatase 
increased 
 
  
Aspartate aminotransferase 
increased 
 
 
 Aspartate 
aminotransferase 
increased (Gr 2) 


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Blood bilirubin increased 
 
  
 
Creatinine increased 
 
 Creatinine increased (Gr 
2) 
 
Ejection fraction decreased 
 
  
 
 
Electrocardiogram QT 
corrected interval prolonged 
  
 
Neutrophil count decreased  
  
METABOLISM AND NUTRITION DISORDERS 
  
Anorexia 
 
 
 Anorexia (Gr 2) 
Metabolism and nutrition 
disorders - Other 
(hyperphosphatemia) 
 
 
 Metabolism and nutrition 
disorders - Other 
(hyperphosphatemia) (Gr 
2) 
NERVOUS SYSTEM DISORDERS 
  
 
Dysgeusia 
 
 Dysgeusia (Gr 2) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Alopecia 
 
 Alopecia (Gr 2) 
 
Dry skin 
 
 Dry skin (Gr 2) 
 
Palmar-plantar 
erythrodysesthesia 
syndrome 
 
  
 
Skin and subcutaneous 
tissue disorders - Other (nail 
disorders)3 
 
 Skin and subcutaneous 
tissue disorders - Other 
(nail disorders)3 (Gr 2) 
1 This 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. 
2 Retinal Pigment Epithelium Detachment (RPED) is characterized as RPED, detachment of macular 
retinal pigment epithelium, subretinal fluid, serous retinal detachment. 
3Nail disorders include nail discoloration, and/or dystrophy. 
Adverse events reported on AZD4547 trials, but for which there is insufficient evidence to 
suggest that there was a reasonable possibility that AZD4547 caused the adverse event: 
CARDIAC DISORDERS - Pericardial effusion; Sinus bradycardia; Sinus tachycardia; 
Supraventricular tachycardia 
EYE DISORDERS - Retinal detachment 
GASTROINTESTINAL DISORDERS - Dyspepsia; Dysphagia; Hemorrhoids; Oral pain 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Edema limbs; Fever; 
Malaise 
HEPATOBILIARY DISORDERS - Hepatobiliary disorders - Other (bile duct obstruction); 
Hepatobiliary disorders - Other (hepatomegaly); Hepatobiliary disorders - Other (jaundice) 
INFECTIONS AND INFESTATIONS - Paronychia; Sepsis; Upper respiratory infection; Urinary 
tract infection 
INVESTIGATIONS - Cardiac troponin T increased; GGT increased; Investigations - Other 
(increase in LVEF) 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hyperkalemia; Hypocalcemia; 
Hypokalemia; Hyponatremia; Hypophosphatemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Back pain; 
Musculoskeletal and connective tissue disorder - Other (groin pain); Pain in extremity 
NERVOUS SYSTEM DISORDERS - Lethargy; Peripheral sensory neuropathy 


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PSYCHIATRIC DISORDERS - Insomnia 
RENAL AND URINARY DISORDERS - Acute kidney injury 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Dyspnea; Epistaxis; Nasal 
congestion; Pleural effusion; Pleuritic pain; Respiratory failure; Respiratory, thoracic and 
mediastinal disorders - Other (breath sounds abnormal) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Rash maculo-papular 
VASCULAR DISORDERS - Hypotension 
NOTE: 
AZD4547 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 4.0. 
All appropriate treatment areas should have access to a copy of the CTCAE 
version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the 
CTEP website (http://ctep.cancer.gov). 
The dose of AZD4547 should be modified according to the dose modification 
guidelines in Section 3.4.1 if any of the following toxicities occur:  
1. Grade 4 neutropenia (ANC < 500/ mm3) 
2. Grade 3 neutropenia (ANC< 1000/ mm3) in the presence of mucositis or for 
more than 7 days 
3. Febrile neutropenia 
4. Grade 3 or greater thrombocytopenia (platelet count < 50,000/mm3 (50 x 
109/L)) in the presence of grade 2 or greater bleeding events.  
5. Grade 4 thrombocytopenia (platelet count < 25,000/mm3 (25 x 109/L)).  
6. Grade 3 or 4 nausea, vomiting, or diarrhea if persistent, despite optimal anti-
emetic and/or anti-diarrheal therapy.  
7. Hyperphosphatemia >7.5 mg/dL. 
8. Any other Grade 4 or unmanageable Grade 3 toxicity.  
9. Refer below (Section 3.4.2) for management of ocular toxicities. 
3.4.1 
AZD4547 Dose Modifications 
Occurrence   
Action to be Taken 
First  
Withhold study drug up to 3 weeks until recovery to Grade 
≤ 1 or baseline; may restart at 60 or 80 mg PO BID. If 
restart at 60 mg PO BID, an effort should be made to 
increase dose to 80 mg PO BID within 4 weeks. 
Second  
Withhold study drug until recovery to Grade ≤1 or 
baseline; restart at 60 mg PO BID. No effort should be 
made to increase dose at 80 mg PO BID. 
Third  
Discontinue AZD4547 permanently 
Dose reductions to 60 mg PO BID are allowed. Dose reductions to 
lower dose levels are not allowed.  
Missed doses should be recorded and considered missed; no effort 
should be made to make up for missed doses. 
Treatment can be withheld due to adverse events up to twice up to 3 
weeks in each occurrence. 
Treatment will be permanently discontinued if treatment has to be 
held for toxicity for the third time or for more than 3 weeks. 


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3.4.2 
Dose Modifications for Ocular Toxicities: 
Figure 1: Management guidelines for patients with visual symptoms of ocular toxicity 
 
Patient has visual symptoms 
or signs of ocular toxicity 
OCT scan shows no evidence of  
RPED/SRF 
If corneal ulceration 
STOP AZD4547 
PERMANENTLY
a 
OCT scan is diagnostic of  
RPED/SRF in macula 
Investigate cause of toxicity and 
manage according to local 
ophthalmological practice 
Stop AZD4547 temporarily. 
Ophthalmologic management as per 
local practice for RPED/SRF. 
Continue on AZD4547 if considered 
appropriate by investigator 
RPED/SRF and visual symptoms 
completely resolved? 
Repeat OCT scan and full 
ophthalmological examination at 3 
weeks 
Continue with protocol frequency of 
ophthalmic assessment 
Repeat OCT and full ophthalmic exam 
after 3 weeks or sooner if visual 
symptoms develop 
If no RPED/SRF, then resume normal 
schedule of protocol assessments.  
Assess sooner if visual symptoms 
develop. 
If RPED/SRF
 recurs  
STOP AZD4547 PERMANENTLY
a 
STOP AZD4547 
PERMANENTLY
a 
Perform full ophthalmological examination including OCT 
Restart AZD4547 at reduced dose
b 
Withhold AZD4547 and 
repeat examination after 
further 3 weeks 
Yes 
No 
RPED/SRF and  
visual symptoms 
resolved? 
No 
Yes 
RPED = Retinal Epithelium 
Detachment 
SRF = Subretinal Fluid 


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Footnotes Figure 1: 
A full ophthalmologic evaluation by an ophthalmologist should involve at least assessment of the visual 
acuity and an optical coherence tomography (OCT) scan plus the following evaluations at the discretion 
of the ophthalmologist: 
1. Amsler grid 
2. Schirmer test without anesthesia 
3. Slit lamp exam 
4. Fundoscopy with attention to retinal abnormalities especially retinal pigment detachment (RPED) and 
subretinal fluid accumulation (SRF) 
5. Corneal examination 
If an active ophthalmologic disease is identified (e.g. retinal detachment), no further testing is required per 
protocol since the patient is ineligible for the study (see Section 2.1.7); the ophthalmologist can proceed 
with further testing and treatment at his/her discretion. 
a:  After permanent discontinuation of AZD4547 due to ocular toxicity, patients should be managed 
according to local clinical practice. 
b: Only 1 dose reduction allowed for management of RPED or SRF. 
MedDRA Medical Dictionary for Regulatory Activities; OCT Optical-coherence-tomography; RPED or SRF 
This grouped term includes RPED (MedDRA preferred terms of detachment of retinal pigment epithelium 
and detachment of macular retinal pigment epithelium), MedDRA preferred term subretinal fluid, MedDRA 
preferred term serous detachment, MedDRA preferred term retinal detachment (MedDRA lower level 
term: serous retinal detachment); SRF Subretinal fluid 
Rev. 12/16 


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Figure 2: Toxicity management guidelines for patients with no visual symptoms of ocular 
toxicity 
 
Re-start AZD4547 at lower dose
b 
STOP AZD4547 PERMANENTLY
c  
Patient has no visual symptoms 
RPED/SRF on routine OCT scan 
(central macula/fovea not affected) 
Continue on AZD4547 at same dose unless considered 
inappropriate by the ophthalmologist and investigator 
Full ophthalmic examination and OCT scan every 3 weeks 
or sooner if visual symptoms develop 
If RPED/SRF progresses
a, temporarily stop AZD4547. 
Repeat OCT scan and full ophthalmological exam after 3 
weeks or sooner if visual symptoms develop. 
If RPED/SRF has resolved or is present 
but has not progressed
a  
If RPED/SRF is present but has 
progressed
a 
Full ophthalmic exam and OCT  
every 3 weeks or sooner if visual 
symptoms develop 
If RPED/SRF progresses
a then 
STOP AZD4547 PERMANENTLY
c 
If RPED/SRF in the central 
macula/fovea follow ‘visual signs 
or symptoms’ flow chart  
Perform full ophthalmological examination including OCT 
RPED = Retinal Epithelium 
Detachment 
SRF = Subretinal Fluid 


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Footnotes Figure 2: 
A full ophthalmologic evaluation by an ophthalmologist should involve at least assessment of the visual 
acuity and an optical coherence tomography (OCT) scan plus the following evaluations at the discretion 
of the ophthalmologist: 
1. Amsler grid 
2. Schirmer test without anesthesia 
3. Slit lamp exam 
4. Fundoscopy with attention to retinal abnormalities especially retinal pigment detachment (RPED) and 
subretinal fluid accumulation (SRF) 
5. Corneal examination 
If an active ophthalmologic disease is identified (e.g. retinal detachment), no further testing is required per 
protocol since the patient is ineligible for the study (see Section 2.1.7); the ophthalmologist can proceed 
with further testing and treatment at his/her discretion. 
a:  Progression of RPED or SRF is defined as development of visual symptoms, extension from para-
macular to macula, or increase in the number of lesions. 
b:  Only 1 dose reduction allowed for management of RPED or SRF. 
c: After permanent discontinuation of AZD4547 due to ocular toxicity, patients should be managed 
according to local clinical practice. 
MedDRA Medical Dictionary for Regulatory Activities; OCT Optical-coherence-tomography; RPED or SRF 
This grouped term includes RPED (MedDRA preferred terms of detachment of retinal pigment epithelium 
and detachment of macular retinal pigment epithelium), MedDRA preferred term subretinal fluid, MedDRA 
preferred term serous detachment, MedDRA preferred term retinal detachment (MedDRA lower level 
term: serous retinal detachment); SRF Subretinal fluid. 
Rev. 12/16 


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3.5 
Supportive Care  
3.5.1 
All supportive measures consistent with optimal patient care will be 
given throughout the study. 
3.5.2 
The following supportive measures are specific for AZD4547 related 
adverse events: 
Organ/toxicity 
Severity 
Action 
Eye 
Xerophthalmia and 
keratitis 
Grade 1and 2 
Lubricating eye drops and replacement tears 
Grade 3 
Withhold AZD4547 until resolution 
RPED* 
Found on routine 
ophthalmology monitoring 
and no visual impairment 
See algorithm for ocular toxicity 
Renal 
Hyperphosphatemia 
Doubling of phosphate 
from baseline or 
Corrected calcium x 
phosphate > 4.5 mmol2/L2 
Start phosphate chelation therapy (sevelamer at 
800 mg PO TID) 
Weekly chemistry assessments until resolution of 
the parameter to below the intervention limit 
Educate patient of low phosphate diet 
Consult Nephrology to assist in the prescription 
and/or titration of phosphate chelators (sevelamer 
up to 1600mg PO TID) 
Continue chelation therapy regardless of the 
resolution to below intervention criteria. 
If no resolution after 14 days of chelation therapy, 
dose reduce to 60mg PO BID, except if already at 
that dose then permanently discontinue AZD4547 
Phosphate levels > 7.5 
mg/dL 
Withhold AZD4547 as outlined in Section 3.4 and 
start chelation therapy as mentioned above. 
Creatinine elevation 
Grade 1 or 2 
Continue treatment; encourage oral hydration 
Grade 3 or 4 
Withhold treatment as outlined in Section 3.4.  
* RPED includes retinal pigmented epithelial detachment, central serous retinopathy, central serous 
choriodopathy, serous detachment. 
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: 
• 
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. 
• 
Patient withdraws consent. 
• 
Patient experiences unacceptable toxicity. 
• 
Non-protocol therapies are administered. 
• 
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 AZD4547 Treatment  
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving AZD4547 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 
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 
β-HCGC 
X 
 
 
 
 
 
Toxicity AssessmentG 
 
X 
X 
 
X 
XF 
Pill Count/DiaryH 
 
X 
 
 
X 
 
ECGK 
X 
 XI 
XI 
 
 
 
Echocardiogram or Nuclear Study (MUGA or First 
Pass) 
X 
 XI 
 
 
 
 
Tumor biopsy and blood sample for MATCH 
Master ProtocolE 
 
 
 
X 
 X 
 
Ophthalmic Exam 
X 
 
 
XI 
 
 
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).  For eligibility purposes, participants with creatinine levels 
above institutional normal, Cockcroft-Gault will be used to calculate creatinine clearance.  CBC w/diff, platelets and serum chemistries should be 
performed on cycle 1, day 1 (or up to 7 days prior), and at the start of each subsequent cycle (up to 3 days before start of new cycle).  CBC with 
differential will be performed more frequently in patients with grade 4 neutropenia or thrombocytopenia until resolution to ≤ grade 3. CBC and 
serum chemistries are only required in follow-up until values return to pre-treatment levels or until progressive disease. 
Rev. 12/16 
Rev. 3/17 
Rev. Add13 


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C. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment. 
D. Disease measurements are repeated every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until PD or start of another MATCH 
treatment step. The baseline evaluation should be performed as closely as possible to the beginning of treatment and never more than 6 weeks 
before registration to the 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: 
• 
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. 
• 
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4). 
• 
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 may be conducted by telephone or in person. The Toxicity Assessment is not required prior to Cycle 1, but is required 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. For eye exam, only when indicated by eye-related symptoms. 
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. 
 


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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. 
Drug Ordering: NCI supplied agents may be requested by the eligible participating 
Investigators (or their authorized designee) at each participating institution. 
Pharmaceutical Management Branch (PMB) policy requires that drug be shipped directly 
to the institution where the patient is to be treated. PMB does not permit the transfer of 
agents between institutions (unless prior approval from PMB is obtained – see general 
information) The CTEP-assigned protocol number must be used for ordering all CTEP-
supplied investigational agents.  The eligible participating investigators at each 
participating institution must be registered with CTEP, DCTD through an annual 
submission of FDA Form 1572 (Statement of Investigator), NCI Biosketch, Agent 
Shipment Form, and Financial Disclosure Form (FDF).  If there are several participating 
investigators at one institution, CTEP-supplied investigational agents for the study 
should be ordered under the name of one lead investigator at that institution. 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 
application (https://ctepcore.nci.nih.gov/OAOP). Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account 
(https://ctepcore.nci.nih.gov/iam) and the maintenance of an “active” account status, a 
“current” password, and an active person registration status. 
NCI Supplied Agent(s) – General Information 
Questions about drug orders, transfers, returns, or accountability should be 
addressed to the PMB by calling 240-276-6575 Monday through Friday between 
8:30 AM and 4:30 PM Eastern Time or email PMBAfterHours@mail.nih.gov 
anytime. 
Drug Returns: All undispensed drug supplies should be returned to the PMB. When it is 
necessary to return study drug (e.g., sealed bottles remaining when PMB sends a stock 
recovery letter), investigators should return the study drug to the PMB using the NCI 
Return Agent Form available on the NCI home page (http://ctep.cancer.gov). 
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. 
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 
Rev. 12/16 
Rev. 3/17 
Rev. Add13 


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5.1 
AZD4547 (NSC 765338) 
5.1.1 
Other Names  
None 
5.1.2 
Classification  
Fibroblast growth factor receptor (FGFR) inhibitor 
5.1.3 
Mode of Action  
AZD4547 is potent and selective inhibitor of the fibroblast growth 
factor receptor (FGFR) -1, 2 and 3 receptor tyrosine kinases and a 
weak inhibitor of both insulin-like growth factor 1 receptor (IGF1R) and 
kinase insert domain receptor (KDR). 
5.1.4 
Storage and Stability  
Store 20 to 25° C (68 to 77° F) in the original container until use. 
Shelf-life studies are ongoing. Dispense tablets in the original, 
unopened containers. Do not repackage tablets in pharmacy bottles 
per the manufacturer’s instructions. 
If a storage temperature excursion is identified, promptly return 
AZD4547 to controlled room temperature 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. 
5.1.5 
Dose Specifics  
AZD4547 is administered at 80 mg PO BID continuously on a 28-day 
cycle. Dose reductions to 60 mg PO BID continuously on a 28-day 
cycle are allowed. 
5.1.6 
Preparation  
AstraZeneca supplies and CTEP, DCTD, NCI distributes AZD4547 as 
beige, round, biconvex, film-coated tablets in 20 mg and 80 mg 
strengths. Tablets are packed in high-density polyethylene (HDPE) 
bottles. Each 20-count bottle is secured with an induction sealed 
membrane and child-resistant closure. 
Each tablet contains active drug substance and the following 
excipients: microcrystalline cellulose, mannitol, magnesium 
carbonate, hydroxypropyl cellulose, sodium starch glycolate and 
glyceryl dibehenate. The film coating contains polyvinyl alcohol, 
titanium dioxide, polyethylene glycol 3350, talc, iron oxide yellow, iron 
oxide red and iron oxide black. 
5.1.7 
Route of Administration  
Oral. Take without regard to meals. 
5.1.8 
Incompatibilities  
In vitro studies demonstrate that AZD4547 is mainly metabolized by 
CYP 3A4/5, 2D6 and 1A1 enzymes. Use caution in patients who are 
taking potent inhibitors or inducers of 3A4/5, 2D6 and 1A1. Smokers 


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may experience reduced drug exposure since tobacco induces 
CYP1A1 activity. AZD4547 is also mainly glucuronidated by UGT1A8 
and 9 isoforms; however, studies indicate a number of other CYP and 
UGT isoforms may be responsible for AZD4547 metabolism. 
In vitro studies demonstrate that AZD4547 is a substrate of 
OATP1B1, does not inhibit p-glycoprotein (P-gp) and is a weak 
inhibitor of OATP1B1 and OCT2. 
In vivo, AZD4547 is a reversible and time-dependent inhibitor of CYP 
3A4/5. Use caution when combining AZD4547 with CYP3A4/5 
substrates known to have a narrow therapeutic window. 
5.1.9 
Side Effects  
See Section 3.3 for side effects. 


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6. 
Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
7. 
References 
1. Dieci MV, Arnedos M, Andre F, Soria JC. Fibroblast growth factor receptor inhibitors 
as a cancer treatment: from a biologic rationale to medical perspectives. Cancer 
discovery 2013;3:264-79. 
2. Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Medicinal 
research reviews 2014;34:280-300. 
3. Gavine PR, Mooney L, Kilgour E, et al. AZD4547: an orally bioavailable, potent, and 
selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. 
Cancer research 2012;72:2045-56. 
4. Andre F, Ranson M, Dean E, et al. Results of a phase I study of AZD4547, an 
inhibitor of fibroblast growth factor receptor (FGFR), in patients with advanced solid 
tumors. Cancer research 2013;73:LB-145. 
5. Paik PK, Shen R, Ferry D, et al. A phase 1b open-label multicenter study of 
AZD4547 in patients with advanced squamous cell lung cancers: Preliminary 
antitumor activity and pharmacodynamic data. J Clin Oncol 2014;32:abstr 8035. 
6. Arkenau H-T, Saggese M, Hollebecque A, et al. A phase 1 expansion cohort of the 
fibroblast growth factor receptor (FGFR) inhibitor AZD4547 in patients (pts) with 
advanced gastric (GC) and gastroesophageal (GOJ) cancer. J Clin Oncol 
2014;32:abstr 2620. 
7. Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes 
in human glioblastoma. Science 2012;337:1231-5. 
8. Tan L, Wang J, Tanizaki J, et al. Development of covalent inhibitors that can 
overcome resistance to first-generation FGFR kinase inhibitors. Proceedings of the 
National Academy of Sciences of the United States of America 2014;111:E4869-77. 
9. Byron SA, Chen H, Wortmann A, et al. The N550K/H mutations in FGFR2 confer 
differential resistance to PD173074, dovitinib, and ponatinib ATP-competitive 
inhibitors. Neoplasia 2013;15:975-88. 
10. Chell V, Balmanno K, Little AS, et al. Tumour cell responses to new fibroblast growth 
factor receptor tyrosine kinase inhibitors and identification of a gatekeeper mutation 
in FGFR3 as a mechanism of acquired resistance. Oncogene 2013;32:3059-70. 
 


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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol W: AZD4547 
Appendix I 
 
Patient Pill Calendar 
Storage: Store at Room Temperature 
Pill Calendar Directions 
1. Take your scheduled dose of each tablet. 
2. If you forget, the missed tablets will not be taken later. 
3. If you vomit after taking your scheduled dose, it will not be made up or re-taken. You 
will continue to receive the next scheduled doses as prescribed 
4. Twice daily doses should be taken at approximately the same time each morning 
and evening approximately 12 hours apart, without regard to meals. 
5. Swallow tablets whole. Do not crush or chew tablets. 
6. Please bring the empty bottle or any leftover tablets and your pill calendar to your 
next clinic visit. 
7. Do not take over the counter calcium supplements, antacids that contain calcium 
(e.g. Tums; Alka-Seltzer Chews; Alcalak; Antacid Calcium Extra Strength; Cal-Gest 
Antacid: Calcium Antacid Extra Strength: Calcium Antacid Ultra Max St; Maalox 
Childrens and some other Maalox formulations; Rolaids; and Titralac), Vitamin D 
supplements (cholecalciferol and ergocalciferol), or laxatives (Fleets Oral, Fleets 
enema and Miralax) without first checking with the Study Doctor. 
8. Avoid consumption of grapefruit, grapefruit hybrids, pumellos, star-fruit, Seville 
oranges or products containing the juice of each within 7 days prior to starting study 
treatment and throughout study treatment. 
9. Do not use tobacco (smoke or chew) while taking this medication – this will make the 
medication less effective. 
 
Rev. 12/16 
Rev. 3/17 


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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. 
AZD4547 
DAY  
Date 
Time 
tablets 
taken 
Number of 
tablets 
taken 
Use the space below to make notes about 
things you would like to tell the doctor 
(including unusual symptoms you experience, 
other medicine you have taken and anything 
else you think would be of interest.) 
Month 
Day 
Year 
AM 
PM 
AM 
PM 
1 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
 
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Patient Signature: __________________________________ Date: _____________ 


ECOG-ACRIN 
EAY131-W 
Cancer Research Group 
Version Date: May 16, 2018 
30 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol W: AZD4547 
Appendix II 
 
Actionable Mutations for Sub-Protocol EAY131-W 
Gene 
Name 
Variant ID 
Variant 
Type 
Variant Description 
Level of 
Evidence 
Code 
FGFR1 
COSM4771556 
SNV 
p.K656M 
3 
FGFR1 
COSM35673 
SNV 
p.K656E 
3 
FGFR2 
COSM29836  
SNV 
p.A648T 
3 
FGFR2 
COSM36906 
SNV 
p.C383R 
3 
FGFR2 
COSM1346276 
SNV 
p.G305R 
3 
FGFR2 
COSM36909 
SNV 
p.K660E 
3 
FGFR2 
COSM683054 
SNV 
p.K659N 
3 
FGFR2 
COSM250083 
SNV 
p.N550H 
3 
FGFR2 
COSM36902 
SNV 
p.N550K 
3 
FGFR2 
COSM36912 
SNV 
p.N550K 
3 
FGFR2 
COSM49170 
SNV 
p.P253R 
2 
FGFR2 
COSM36903 
SNV 
p.S252W 
3 
FGFR2 
COSM36904 
SNV 
p.Y376C 
3 
FGFR3 
COSM721 
SNV 
p.A393E 
3 
FGFR3 
COSM716 
SNV 
p.G372C 
3 
FGFR3 
COSM24842 
SNV 
p.G382R 
3 
FGFR3 
COSM24802 
SNV 
p.G699C 
3 
FGFR3 
COSM719 
SNV 
p.K652E 
3 
FGFR3 
COSM720 
SNV 
p.K652M 
3 
FGFR3 
COSM726 
SNV 
p.K652Q 
3 
FGFR3 
COSM731 
SNV 
p.K652T 
3 
FGFR3 
COSM714 
SNV 
p.R248C 
3 
FGFR3 
COSM715 
SNV 
p.S249C 
2 
FGFR3 
COSM17461 
SNV 
p.S373C 
3 
FGFR3 
COSM718 
SNV 
p.Y375C 
3 
FGFR1 
COSM48380  
SNV 
p.T141R 
2 
FGFR2 
COSM4994845  
SNV 
p.S252L 
2 
FGFR2 
COSM250081  
SNV 
p.V395D 
2 
Rev. 12/16 


ECOG-ACRIN 
EAY131-W 
Cancer Research Group 
Version Date: May 16, 2018 
31 
FGFR2 
COSM36913 
SNV 
p.I547V 
2 
FGFR2 
COSM4604460  
SNV 
p.N549D 
2 
FGFR2 
COSM3665555 
SNV 
p.N549S 
2 
FGFR3 
COSM296687 
SNV 
p.R399C 
2 
FGFR3 
COSM29438  
SNV 
p.D641N 
2 
FGFR3 
COSM732992 
SNV 
p.K715M 
2 
FGFR3 
FGFR3-AES.F17A2 
Fusion 
FGFR3-AES.F17A2 
3 
FGFR3 
FGFR3-
BAIAP2L1.F17B2.COSF1347 
Fusion 
FGFR3-
BAIAP2L1.F17B2.COSF1347 
3 
FGFR3 
FGFR3-ELAVL3.F17E2 
Fusion 
FGFR3-ELAVL3.F17E2 
3 
FGFR3 
FGFR3-TACC3.F14T11 
Fusion 
FGFR3-TACC3.F14T11 
3 
FGFR3 
FGFR3-TACC3.F15T11 
Fusion 
FGFR3-TACC3.F15T11 
3 
FGFR3 
FGFR3-
TACC3.F16T10.COSF1359 
Fusion 
FGFR3-
TACC3.F16T10.COSF1359 
3 
FGFR3 
FGFR3-
TACC3.F16T11.COSF1348 
Fusion 
FGFR3-
TACC3.F16T11.COSF1348 
3 
FGFR3 
FGFR3-TACC3.F17intron17T4 
Fusion 
FGFR3-TACC3.F17intron17T4 
3 
FGFR3 
FGFR3-TACC3.F17Intron17T9 
Fusion 
FGFR3-TACC3.F17Intron17T9 
3 
FGFR3 
FGFR3-TACC3.F17T10 
Fusion 
FGFR3-TACC3.F17T10 
3 
FGFR3 
FGFR3-
TACC3.F17T10.COSF1434 
Fusion 
FGFR3-
TACC3.F17T10.COSF1434 
3 
FGFR3 
FGFR3-TACC3.F17T11 
Fusion 
FGFR3-TACC3.F17T11 
3 
FGFR3 
FGFR3-TACC3.F17T11.1 
Fusion 
FGFR3-TACC3.F17T11.1 
3 
FGFR3 
FGFR3-TACC3.F17T11.2 
Fusion 
FGFR3-TACC3.F17T11.2 
3 
FGFR3 
FGFR3-TACC3.F17T13.NGS 
Fusion 
FGFR3-TACC3.F17T13.NGS 
3 
FGFR3 
FGFR3-TACC3.F17T5 
Fusion 
FGFR3-TACC3.F17T5 
3 
FGFR3 
FGFR3-TACC3.F17T6 
Fusion 
FGFR3-TACC3.F17T6 
3 
FGFR3 
FGFR3-TACC3.F17T7  
Fusion 
FGFR3-TACC3.F17T7  
3 
FGFR3 
FGFR3-TACC3.F17T8 
Fusion 
FGFR3-TACC3.F17T8 
3 
FGFR3 
FGFR3-TACC3.F17T9 
Fusion 
FGFR3-TACC3.F17T9 
3 
FGFR3 
FGFR3-TACC3.F18T10 
Fusion 
FGFR3-TACC3.F18T10 
3 
FGFR3 
FGFR3-TACC3.F18T10.1 
Fusion 
FGFR3-TACC3.F18T10.1 
3 
FGFR3 
FGFR3-TACC3.F18T11 
Fusion 
FGFR3-TACC3.F18T11 
3 
FGFR3 
FGFR3-TACC3.F18T4and5 
Fusion 
FGFR3-TACC3.F18T4and5 
3 
FGFR3 
FGFR3-TACC3.F18T7.NGS 
Fusion 
FGFR3-TACC3.F18T7.NGS 
3 
FGFR3 
FGFR3-
TACC3.TruncatedF17T4 
Fusion 
FGFR3-
TACC3.TruncatedF17T4 
3 
FGFR2 
FGFR2-AFF3.F17A8 
Fusion 
FGFR2-AFF3.F17A8 
3 


ECOG-ACRIN 
EAY131-W 
Cancer Research Group 
Version Date: May 16, 2018 
32 
FGFR2 
FGFR2-BICC1.F17B2 
Fusion 
FGFR2-BICC1.F17B2 
3 
FGFR2 
FGFR2-CASP7.F17C2 
Fusion 
FGFR2-CASP7.F17C2 
3 
FGFR2 
FGFR2-CIT.F17C23 
Fusion 
FGFR2-CIT.F17C23 
3 
FGFR2 
FGFR2-
KIAA1967_CCAR2.F17C4 
Fusion 
FGFR2-
KIAA1967_CCAR2.F17C4 
3 
FGFR2 
FGFR2-MGEA5.F17M12 
Fusion 
FGFR2-MGEA5.F17M12 
3 
FGFR2 
FGFR2-OFD1.F17O3 
Fusion 
FGFR2-OFD1.F17O3 
3 
FGFR2 
FGFR2-TACC3.F17T11 
Fusion 
FGFR2-TACC3.F17T11 
3 
FGFR2 
SLC45A3-FGFR2.S1F1 
Fusion 
SLC45A3-FGFR2.S1F1 
3 
FGFR2 
SLC45A3-FGFR2.S1F2 
Fusion 
SLC45A3-FGFR2.S1F2 
3 
FGFR1 
BAG4-FGFR1.B1F8 
Fusion 
BAG4-FGFR1.B1F8 
3 
FGFR1 
BAG4-FGFR1.B2F6 
Fusion 
BAG4-FGFR1.B2F6 
3 
FGFR1 
ERLIN2-FGFR1.E8F2 
Fusion 
ERLIN2-FGFR1.E8F2 
3 
FGFR1 
FGFR1-TACC1.F17T7 
Fusion 
FGFR1-TACC1.F17T7 
3 


ECOG-ACRIN 
EAY131-W 
Cancer Research Group 
Version Date: May 16, 2018 
33 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol W: AZD4547 
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, AZD4547.  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: 
AZD4547 interacts with certain enzymes in the liver and certain transport proteins that help 
move drugs in and out of cells. 
• 
The enzymes in question are CYP 3A4/5, 2D6, 1A1, and UGT1A8/9. AZD4547 is broken 
down by these enzymes and may be affected by other drugs that strongly inhibit or induce 
these enzymes. AZD4547 inhibits CYP 3A4/5 and may affect other drugs that are broken 
down by these enzymes. 
• 
The transport proteins in question are OATP1B1 and OCT2. AZD4547 requires OATP1B1 to 
move and out of cells. AZD4547 is an inhibitor of OATP1B1 and OCT2 transport proteins 
and may affect transport of other drugs that require these proteins to move in and out of 
cells. 
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet. 
AZD4547 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. 
These are the things that you and they need to know: 
AZD4547 must be used very carefully with other medicines that use certain liver enzymes and 
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 CYP 
3A4/5, 2D6, 1A1, UGT1A8/9 or OATP1B1 or substrates of CYP 3A4/5 and transport proteins 
OATP1B1 and OCT2.”  These characteristics may change how AZD4547 or other medicine 
works in your body. 


ECOG-ACRIN 
EAY131-W 
Cancer Research Group 
Version Date: May 16, 2018 
34 
• 
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. 
• 
Avoid ingesting grapefruit juice, grapefruit and Seville oranges while taking AZD4547. 
• 
Avoid smoking or use of tobacco products as they may affect how AZD4547 works in your 
body. 
• 
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 AZD4547.  This clinical trial 
is sponsored by the NCI.  AZD4547 may interact with 
drugs that are processed by your liver, or use certain 
transport proteins in your body.  Because of this, it is 
very important to: 
 Tell your doctors if you stop taking any medicines 
or if you start taking any new medicines. 
 Tell all of your health care providers (doctors, 
physician assistants, nurse practitioners, or 
pharmacists) that you are taking part in a clinical 
trial. 
 Check with your doctor or pharmacist whenever 
you need to use an over-the-counter medicine or 
herbal supplement. 
 Avoid ingesting grapefruit, grapefruit juice and 
Seville oranges and avoid smoking or use of 
tobacco products while on trial.
 AZD4547 interacts with CYP 3A4/5, 2D6, 1A1, 
UGT1A8/9 and transport proteins OATP1B1 and 
OCT2 and must be used very carefully with other 
medicines that interact with these enzymes and 
transport proteins. 
 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 CYP 
3A4/5, 2D6, 1A1, UGT1A8/9 or OATP1B1 or 
substrates of CYP3A4/5 and transport proteins 
OATP1B1 or OCT2.”  
 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. 
Your study doctor’s name is 
_____________________________ and can be 
contacted at _________________________________.