Clinical trial NCT04504331
Conditions: Breast Cancer HER2-negative Breast Cancer ER Positive Breast Cancer PR-Positive Breast Cancer
Sponsor: Jennifer Lee Caswell-Jin
Start date: 2020-10-13; Completion date: 2021-10-22
Enrollment: 4 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of the study is identify the dose(s) of infigratinib to use in combination with tamoxifen to treat patients with a particular type of advanced breast cancer (hormone receptor-positive, HER2-negative, FGFR-altered breast cancer)

Detailed description:
Primary Objective: Determine the maximum (no greater than 125 mg) dose of infigratinib used in combination with the FDA-approved dose and schedule of tamoxifen (Cohort 1) in terms of the number of dose-limiting toxicities observed in the first 2 cycles of therapy in subjects with hormone receptor-positive, HER2-negative advanced breast cancer.

Secondary Objective:

* Estimate the incidence of treatment-emergent adverse events (serious and non-serious).
* Estimate the objective tumor response rate (ORR) in subjects with measurable disease.
* Estimate the progression-free survival (PFS).
* Estimate the durable clinical benefit rate.

Arms: arm 1: In study part 1 (dose exploration), participants will receive up to infigratinib 100 mg. 100 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen arm 2: In study part 1 (dose exploration), participants will receive up to infigratinib 125 mg. 125 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/ day tamoxifen arm 3: In study part 1 (dose exploration), participants will receive up to infigratinib 75 mg. 75 mg of Infigratinib will be administered orally daily, 3 weeks on, 1 week off + 20 mg/day tamoxifen
Interventions: intervention 1: Infigratinib intervention 2: Tamoxifen intervention 3: Omnipaque 350 intervention 4: Iopamidol intervention 5: Computed tomography (CT)
Intervention descriptions: intervention 1: Oral dose intervention 2: Oral Dose intervention 3: IV contrast agent intervention 4: IV contrast agent intervention 5: Computed tomography (CT) to assess disease state using Iopamidol and/or Omnipaque 350.

Protocol documents:
Prot_SAP_001.pdf: 
A Phase 1B Study of Infigratinib in Combination with Tamoxifen in  
Hormone Receptor-positive, HER2-negative, FGFR-altered Advanced Breast Cancer  
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11 November 2021 
A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone 
Receptor-Positive, HER2-Negative, FGFR-Altered Advanced Breast Cancer  
Coordinating Center 
Stanford Cancer Institute 
875 Blake Wilbur Drive 
Stanford, CA  94305  
Protocol Director  
Jennifer L Caswell-Jin, MD 
Assistant Professor of Medicine (Oncology) 
269 Campus Dr, CCSR 1145C 
Stanford Medicine at Stanford University; M/C 5769 
Stanford, CA  94305-5769 
Telephone:  650-724-3250 
e-mail:  caswell@stanford.edu   
Sub-Investigators 
George W Sledge, Jr, MD 
Professor of Medicine 
Stanford Medicine at Stanford Univ M/C 5151 
269 Campus Drive West; CCSR 1115  
Stanford, CA 94305-5151 
Phone  650-724-4397 
e-mail:  gsledge@stanford.edu 
Christina Curtis, PhD, MSc 
Assistant Prof of Medicine (Oncology) & Genetics 
Lorry Lokey Building/SIM1 Campus Dr, Suite G2120C  
Stanford Medicine at Stanford Univ  
Stanford, CA 94305 
Tel:  650-498-9943 
e-mail:  cncurtis@stanford.edu  
Biostatisticians 
Kristen Cunanan, PhD 
1701 Page Mill Road 
Palo Alto, CA 94304 
Tel:  650-723-7356 
e-mail:  cunanank@stanford.edu 
Manisha Desai, PhD 
1070 Arastradero Road, Room 305 
Palo Alto, CA 94304 
Tel:  650-725-1946 
e-mail:  manisha.desai@stanford.edu 
Vandana Sundaram, MPH 
1701 Page Mill Road 
Stanford, CA 94305 
Telephone:  650-736-4367 
e-mail:  sund@stanford.edu 
Clinical Research Coordinator 
Allison Zhang, MPH 
780 Welch Road 
Palo Alto, CA 94305 
Telephone:  650-736-5790 
e-mail:  axkong@stanford.edu 
 
 
IRB-53650  
BRS0113 
IND-149509 
NCT04504331 
Version 11 / Version Date:  11 November 2021  
Initial SRC Approval Date:  06 April 2020 (for version 27 March 2020)   


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TABLE OF CONTENTS  
PROTOCOL SYNOPSIS ............................................................................................................ 6 
SCHEMA .................................................................................................................................... 8 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................................... 9 
1. 
OBJECTIVES ................................................................................................................ 10 
1.1. 
PRIMARY OBJECTIVE ....................................................................................................... 10 
1.2. 
SECONDARY OBJECTIVES ................................................................................................ 10 
1.3. 
EXPLORATORY OBJECTIVES ............................................................................................. 10 
2. 
BACKGROUND ............................................................................................................ 10 
2.1 
STUDY DISEASE .............................................................................................................. 10 
2.2 
STUDY AGENT................................................................................................................. 11 
2.3 
RATIONALE ..................................................................................................................... 19 
2.4 
SCREENING TUMOR SEQUENCING ASSAYS ....................................................................... 21 
2.5 
STUDY DESIGN ............................................................................................................... 21 
2.6 
CORRELATIVE STUDIES BACKGROUND ............................................................................. 22 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ............................. 23 
3.1 
INCLUSION CRITERIA ....................................................................................................... 24 
3.2 
EXCLUSION CRITERIA ...................................................................................................... 27 
3.3 
INFORMED CONSENT PROCESS ........................................................................................ 31 
3.4 
STUDY TIMELINE ............................................................................................................. 31 
4. 
TREATMENT PLAN ...................................................................................................... 31 
4.1  
GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE GUIDELINES ....................... 32 
4.2 
CRITERIA FOR REMOVAL FROM STUDY ............................................................................. 36 
4.3 
ALTERNATIVES ................................................................................................................ 37 
5. 
INVESTIGATIONAL AGENT INFORMATION ............................................................... 37 
5.1 
INVESTIGATIONAL AGENT ................................................................................................. 37 
5.2 
AVAILABILITY ................................................................................................................... 38 
5.3 
AGENT ORDERING ........................................................................................................... 38 
5.4 
AGENT ACCOUNTABILITY ................................................................................................. 39 
6. 
DOSE MODIFICATIONS ............................................................................................... 39 
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES ............................................. 47 


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7.1 
POTENTIAL ADVERSE EVENTS .......................................................................................... 47 
7.2 
ADVERSE EVENTS DEFINITIONS ....................................................................................... 48 
7.3 
ADVERSE EVENTS REPORTING......................................................................................... 49 
7.4 
REPORTING SERIOUS ADVERSE EVENTS .......................................................................... 49 
7.5 
PREGNANCY ................................................................................................................... 50 
8. 
CORRELATIVE/SPECIAL STUDIES ............................................................................ 51 
8.1 
LABORATORY CORRELATIVE STUDIES .............................................................................. 51 
9. 
STUDY CALENDAR ..................................................................................................... 53 
10. 
MEASUREMENTS ........................................................................................................ 58 
10.1  
PRIMARY ENDPOINT ......................................................................................................... 58 
10.2  
SECONDARY ENDPOINTS .................................................................................................. 60 
10.3  
OUTCOMES FOR CLINICALTRIALS.GOV .............................................................................. 60 
11. 
REGULATORY CONSIDERATIONS ............................................................................ 62 
11.1 
INSTITUTIONAL REVIEW OF PROTOCOL ............................................................................. 62 
11.2 
DATA SHARING WITH COLLABORATORS  ........................................................................... 62 
11.3 
DATA AND SAFETY MONITORING PLAN .............................................................................. 62 
11.4 
DATA MANAGEMENT PLAN ............................................................................................... 63 
12. 
STATISTICAL CONSIDERATIONS .............................................................................. 63 
12.1 
STATISTICAL DESIGN AND SAMPLE SIZE DETERMINATION .................................................. 63 
12.2 
INTERIM ANALYSES ......................................................................................................... 63 
12.3 
DESCRIPTIVE STATISTICS AND EXPLORATORY DATA ANALYSIS .......................................... 63 
12.4 
PRIMARY SAFETY ANALYSIS............................................................................................. 63 
12.5 
SECONDARY SAFETY ANALYSIS ....................................................................................... 64 
12.6 
EFFICACY ANALYSIS ........................................................................................................ 64 
12.7 
ANALYSIS POPULATION .................................................................................................... 65 
12.8 
ACCRUAL CONSIDERATIONS ............................................................................................ 65 
12.9 
CRITERIA FOR FUTURE STUDIES ...................................................................................... 65 
13. 
REFERENCES .............................................................................................................. 66 
APPENDICES........................................................................................................................... 69 
APPENDIX A:  LIST OF PROHIBITED MEDICATIONS AND SUBSTANCES  .......................................... 69 
APPENDIX B:  LIST OF DRUGS TO BE USED WITH CAUTION WHILE ON STUDY ............................... 70 


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APPENDIX C:  RECIST V1.1 ..................................................................................................... 71 
 
Document History 
Date 
Summary 
27 March 2020 
Initial version to SRC (approved 6 April 2020) 
29 April 2020 
 
Document History table added 
 
Number of subjects corrected (up to 36 total) 
 
Cohort 1 dose levels clarified 
 
ClinicalTrials.gov outcomes adjusted 
 
Minor typography and syntax 
30 July 2020 
 
Cohort 1 infigratinib dose levels increased from 2 dose levels (100 mg and 125 mg) to 
3 dose levels (75 mg, 100 mg, and 125 mg). 
 
Cohort 1 recommended infigratinib dose when 0 of 3 or 1 of 6 subjects experience a DLT 
in their first 2 cycles at that dose. 
 
Intra-subject dose escalation allowed in Cohort 1 only, such that if a subject starts at 
infigratinib 100 mg and remains on-study after 2 cycles with no DLTs seen, they will 
begin receiving infigratinib 125 mg, and the number of DLTs in Cycles 3 and 4 will count 
toward the primary endpoint in Cohort 1 at this dose. 
 
Number of subjects adjusted for Cohort 1 (minimum 3 total instead of 6 total) and for both 
Cohorts together (maximum 33 instead of 36). 
 
Clarification for Cohort 2 that expansion to 12 subjects at recommended dose should 
include N = 6 IC2, and N = 6 IC6. 
 
Multiplexed ion beam imaging (MIBI) mentioned as another possible in situ proteomic 
method for exploratory analysis, in addition to Digital Spatial Profiling (DSP)  
 
Research tissue biopsies to be sent to the Curtis lab for processing 
21 August 2020  
Administrative changes, updates, and corrections  
31 August 2020  
Moved ondansetron from Appendix A to Appendix B. 
 
Corrections to the following: 
o 
Cohort 2 treatment group numbering as 4 to 6, not 3 to 5 (in Section 2.5). 
o 
Table 4 was mislabeled as Figure 1 (in section 2.5).  
o 
AE drug relationship are to be determined for infigratinib, tamoxifen (Cohort 1);  
fulvestrant (Cohort 2);  or palbociclib (Cohort 2), removing gemcitabine plus cisplatin 
(in Section 7.3). 
o 
REDCap will be used as data management, rather than OnCore (in Section 11.3). 
 
Administrative changes, updates, and corrections, including the addition of hyperlinks 
(not highlighted)  


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23 Sept 2020 
 
QED Therapeutics will be notified within 24 hours of learning of occurrence of an SAE, 
Suspected Unexpected Serious Adverse Reactions or pregnancy event (Sections 7.4 and 
7.5), instead of within 7 days. 
 
QED Therapeutics will supply the Case Report Forms for SAE and Pregnancy events to 
be reported to QED.  QED may be notified via by email (SAEintake@covance.com) using 
their provided CRFs or upload to electronic SAE portal (Sections 7.4 and 7.5). 
 
Instead of within 7 days, Suspected Unexpected Serious Adverse Reactions will be 
submitted to the FDA via an IND amendment within 15 days, and within 7 days for 
life-threatening conditions and death (Section 7.4), to match with the defined FDA 
guidance document on reporting. 
 
Eliminating pharmacokinetics assessments per QED Therapeutics, as the data collection 
is no longer required 
1 Oct 2020 
Removes Cohort 2 throughout 
9 Oct 2020 
The frequency of echocardiogram (ECHO) monitoring has been adjusted to Baseline, 
Cycle 2 Day 1, and End of Treatment. 
5 Apr 2021 
 
Dr. Jennifer Caswell-Jin is assuming the role of IND-holder, Principal Investigator, and 
Protocol Director. 
 
In Section 5.1.2, the allowed dosing time interval for infigratinib was revised to be 
24 ± 4 hour for consistency with the Pharmacy Manual (Section 7.0).  Clarified that 
infigratinib should be dosed in the morning when possible, with the understanding that 
there may be scheduling limitations at times (eg, delay in drug dispense on days with 
clinic visit). 
 
Updated Study Calendar (Section 9).  
o 
Added Complete Metabolic Panel as an optional assessment in the “Other 
Follow-up” timepoint. 
o 
Clarified in footnote 25 that only clinical indicated assessments need to be performed 
beyond 30 days.  
o 
Clarified that “End of Treatment/Withdrawal” should be 0 to 14 days from the 
decision made to discontinue study treatment (previously 0 to 14 days from 
final dose) to match footnote 23. 
 
Administrative changes, updates, and corrections 
28 Oct 2021 
 
Updates regulatory status information for infigratinib (Section 2.2)  
 
Updates Participant Selection and Enrollment Procedures (Section 3) to identify the 3rd 
reviewer of eligibility to be a member of the study team (eg, investigator or back-up study 
coordinator) 
 
Specifies / elaborates that the tamoxifen dosing window is 4 to 8 hours after infigratinib 
administration. 
 
Identifies QED Therapeutic’s partner, the Helsinn Group, throughout the protocol, 
including for data sharing / access (Section 11.2).  
 
Administrative changes, updates, and corrections.  
11 Nov 2021 
 
Updates safety reporting in sections 7.4 and 7.5, per manufacturer’s request 
 


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PROTOCOL SYNOPSIS 
TITLE 
A Phase 1B Study of Infigratinib in Combination with 
Tamoxifen in Hormone Receptor-Positive, HER2-Negative 
FGFR-Altered Advanced Breast Cancer 
STUDY PHASE 
1B 
INDICATION 
Advanced breast cancer, ER and/or PR+, HER2-.  Additional 
inclusion and exclusion criteria outlined in n Section 3.1 and 
Section 3.2. 
INVESTIGATIONAL 
PRODUCT  
Cohort 1:  Infigratinib + Tamoxifen  
PRIMARY 
OBJECTIVE 
Identify the recommended dose of infigratinib to be used in 
combination with the FDA-approved dose and schedule of tamoxifen. 
SECONDARY 
OBJECTIVES 
1. Estimate the incidence of treatment-emergent adverse events.  
2. Estimate the objective tumor response rate.  
3. Estimate progression-free survival.  
4. Estimate the clinical benefit rate. 
EXPLORATORY 
OBJECTIVES 
1. Establish viable tumor-derived organoid cultures to study in vitro 
tumor response to combination targeted therapy.  
2. Examine cell-free DNA from plasma across therapy to identify 
markers of therapeutic resistance.  
3. Examine tumor and microenvironmental changes across therapy 
using in situ proteomics. 
STUDY 
POPULATION 
Eligible subjects will be adults with ER-positive and/or PR-positive, 
HER2-negative breast cancer and radiographic evidence of 
metastatic disease, or locally recurrent unresectable disease.  
Women must be postmenopausal.  Due to length, the Eligibility 
Criteria are only presented in one instance.  See Section 3 
Participant Selection and Enrollment Procedures. 


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PROTOCOL SYNOPSIS 
TREATMENT 
SUMMARY 
Infigratinib is an oral selective FGFR1-3 inhibitor that has been tested 
in phase 1 and 2 clinical trials as a single agent.  This phase 1B 
study will assess the safety and tolerability of infigratinib in 
combination with the FDA-approved dose and schedule of tamoxifen 
(Cohort 1).  In Cohort 1, up to 3 dose levels of infigratinib will be 
evaluated:  125 mg;  100 mg;  and 75 mg, starting with the middle 
dose level (100 mg).  Infigratinib will be administered orally daily, 
3 weeks on, 1 week off.  Subjects will also be given tamoxifen 20 mg 
orally continuously.  If toxicity presents, individual subjects may 
dose-reduce by 25 mg infigratinib per reduction, to a lower limit of 
75 mg infigratinib (See Sections 2.5 and 6).  
Treatment with study drug will continue for 18 months or confirmed 
disease progression, unacceptable toxicity deemed probably-related 
to study drug, whichever occurs first, or other reasons outlined in 
Section 4.3.  
SAMPLE SIZE  
Up to 12 subjects evaluable (minimum 3), not including subject 
replacement.  
 


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SCHEMA  
  
Eligible patients
•
Metastatic or locally recurrent 
unresectable breast cancer
•
ER+ or PR+
•
HER2-
•
ECOG 0-2
Cohort 1
• Infigratinib 125 or 100 or 75 mg 
(3+3) orally daily 3 weeks on, 1 
week off, starting with 100 mg
• Tamoxifen 20 mg orally daily 
continuously
Primary endpoint:
Incidence of dose-limiting toxicities in 
cycles 1-2
Secondary endpoints:
Incidence of treatment-emergent 
adverse events
Objective tumor response
Progression-free survival
Durable clinical benefit
IC2 or 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse event 
ASCO-CAP 
American Society of Clinical Oncology-College of American Pathologists 
CBC 
Complete blood count 
CLIA 
Clinical Laboratory Improvement Amendments 
CNS 
Central nervous system 
CR 
Complete Response 
CRF 
Case report/record form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
Circulating tumor deoxyribonucleic acid 
CYP3A 
Cytochrome P450 3A 
DLT 
Dose-limiting Toxicity 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram  
ER 
Estrogen receptor 
FDA 
Food and Drug Administration 
FFPE 
Formalin-fixed paraffin-embedded 
FGF 
Fibroblast growth factor 
FGFR 
Fibroblast growth factor receptor 
FISH 
Fluorescence in situ hybridization 
HR 
Hormone receptor 
IC 
Integrative Cluster 
IHC 
Immunohistochemistry 
IRB 
Institutional Review Board 
LLN  
Lower limit of normal 
MAD 
Maximum administered dose 
METABRIC 
Molecular Taxonomy of Breast Cancer International Consortium 
MTD 
Maximum tolerated dose 
OCT 
Optical coherence tomography 
ORR 
Objective response rate  
PFS 
Progression-free survival  
PD 
Progressive Disease 
PR 
Progesterone receptor 
RECIST 
Response evaluation criteria in solid tumors 
RR 
Response rate 
SAE 
Serious adverse event 
SD 
Stable disease 
TCGA 
The Cancer Genome Atlas 
TEAE 
Treatment-emergent adverse event 


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1. 
OBJECTIVES  
1.1. 
Primary Objective  
 
Determine the maximum (no greater than 125 mg) dose of infigratinib used in 
combination with the FDA-approved dose and schedule of tamoxifen (Cohort 1), in terms 
of the number of dose-limiting toxicities observed in the first 2 cycles of therapy in 
subjects with hormone receptor-positive, HER2-negative advanced breast cancer.  
1.2. 
Secondary Objectives  
 
Estimate the incidence of treatment-emergent adverse events (serious and non-serious).  
 
Estimate the objective tumor response rate (ORR) in subjects with measurable disease.  
 
Estimate the progression-free survival (PFS).  
 
Estimate the durable clinical benefit rate.  
1.3. 
Exploratory Objectives  
 
Establish viable tumor-derived organoid cultures to study in vitro tumor response to 
combination targeted therapy  
 
Examine cell-free DNA from plasma across therapy to identify markers of therapeutic 
resistance  
 
Examine tumor and microenvironmental changes across therapy using in situ 
proteomics.  
2. 
BACKGROUND  
2.1 
Study Disease  
Advanced-stage, or metastatic, breast cancer remains incurable in the vast majority of cases, 
with an estimated median survival of approximately 3 years. 1  Hormone receptor-positive (HR+) 
disease is generally viewed as less aggressive than triple-negative or HER2+ breast cancer, but 
recent data from our group suggest that a subset of HR+ breast cancers are highly aggressive, 
exhibiting recurrence rates higher than triple-negative breast cancers or HER2+ breast cancers 
in the era prior to trastuzumab. 2  These high-risk HR+ breast cancer subtypes classify as one of 
four integrative clusters (ICs or “IntClusts”), each defined by a characteristic gene amplification 
as follows. 2,3  
 
IC1, defined by RPS6KB1 (17q23)  
 
IC2, defined by FGF3/4/19 and CCND1 (11q13).  IC2 is associated with a poor 
prognosis amongst ER-positive tumors, with a 10-year disease-specific survival rate of 
only about 50%.  
 
IC6, defined by FGFR1 (8p12).  IC6 is associated an intermediate prognosis and a 
10-year disease-specific survival of around 60%.  
 
IC9, defined by MYC (8q24)  


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Notably for IC2, FGF3/4/19 and CCND1 are tightly located within the 11q13 genomic region and 
are almost universally amplified together as a cassette in breast cancer; 2,3 thus amplification of 
either is generally consistent with amplification of both.  FGFR1 amplifications occur in 
approximately 10% and CCND1/FGF3/4/19 amplifications in approximately 6% of early-stage 
ER+/HER2- breast cancers; 2,3  proportions are likely higher in advanced-stage breast cancer 
given the higher rates of recurrence.  While these characteristic amplifications are almost 
universally present within tumors classifying as the relevant integrative subtype, the converse is 
not true:  in the METABRIC cohort, approximately one quarter of HR+/HER2- tumors that carry 
the CCND1 amplification classify as integrative subtype 2, and approximately half of those that 
carry the FGFR1 amplification classify as integrative subtype 6.  It is plausible that these 
amplifications may be passenger events rather than driver events in the tumors that do not 
classify as the relevant integrative subtypes.  
The current treatment paradigm for these tumors does not include testing for integrative subtype 
or targeting the subtype-defining gene amplifications.  Metastatic HR+/HER2- breast cancer is 
typically treated in the first line with endocrine therapy (most commonly an aromatase inhibitor), 
often in combination with a CDK4/6 inhibitor 4-6; in the second line, endocrine therapy is 
typically used again, either alone, in combination with a CDK4/6 inhibitor if not used in the 
first-line 7-9, or in combination with an mTOR inhibitor. 10  After progression on two lines of 
endocrine therapy, the disease is often considered endocrine-resistant and treated with 
sequential single-agent chemotherapies until progression. 11  There is an urgent need to find 
more effective therapies for HR+/HER2- metastatic breast cancer, and we hypothesize that 
targeting the FGFR axis in tumors that may be driven by FGFR signaling, as defined either by 
amplification or integrative subtype, may improve outcomes for patients with these tumor types.  
This study evaluates the safety and efficacy of infigratinib, an FGFR 1 to 3 inhibitor, in 
combination treatment for eligible HR+/HER2- breast cancer patients whose tumors classify as 
the IC2 or IC6 subtypes (see criterion 2 in Section 3.1).  As noted above, IC2 and IC6 are 
associated with alternations in FGF and/or FGFR. 
2.2 
Study Agent - Infigratinib  
2.2.1 Regulatory status:  Infigratinib (BGJ398) was approved by FDA as Truseltiq pursuant the 
Accelerated Approval regulations on 28 May 2021 for the indication of previously-treated, 
unresectable, locally-advanced or metastatic cholangiocarcinoma with a fibroblast growth factor 
receptor 2 (FGFR2) fusion or other rearrangement, in adults.  
2.2.2 Mechanism of action:  Infigratinib (BGJ398) is an orally-bioavailable, potent, selective 
inhibitor of the fibroblast growth factor receptors (FGFR 1-3, but 60-fold less active on FGFR4).  
The FGFR family of receptor tyrosine kinases consists of four members (FGFR1-4), which serve 
as the high affinity receptors for 22 FGF ligands.  These growth factors control cell proliferation, 
migration, angiogenesis, apoptosis, and differentiation.  A subfamily of FGF ligands including 
FGF19 additionally act as endocrine hormones. 12  
2.2.3 Pharmacokinetics:  The pharmacokinetics of infigratinib was investigated in mouse, rat, 
and dog after oral and intravenous administration.  In all 3 species, the clearance and the 


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volume of distribution at steady state was high.  The terminal elimination half-life in plasma was 
9.3 hours in mouse, 4.5 hours in rat, and 3.1 hours in dog.  The absolute bioavailability was 
2.4% in dog and approximately 30% in mouse and rat.  In oncology patients, the mean terminal 
elimination half-life on Day 1 was 3 to 7 hours; accumulation was observed with daily dosing at 
doses ≥ 60 mg, with mean accumulation ratio ranging from 3 to 8 on Day 15 and Day 28.  
2.2.4 Metabolism:  The in vitro metabolism of [14C]-infigratinib was studied in hepatocytes from 
rat, dog, and human.  Two main biotransformation pathways were observed in all species 
investigated:  N-oxidation to BQR917 (predominant pathway in dog) and D-deethylation to 
BHS697 (predominant pathway in human) (in rat, the two pathways were of similar importance).  
Additional biotransformation pathways included glutathione conjugation, O-demethylation, 
hydrolysis, C-hydroxylation, and others.  The in vivo metabolism of [14C]-infigratinib was studied 
in rats and dogs, and of unlabeled infigratinib in dogs and humans.  13 metabolites were 
identified and semi-quantified in human plasma with the cleavage product CQM157 the most 
abundant one; all except 1 minor metabolite were also detected in rat and/or dog plasma after 
oral dosing.  
2.2.5 Major route of elimination:  The major route of elimination in rats and dogs dosed orally or 
intravenously with [14C]-infigratinib was the feces.  Urinary excretion amounted to ≤ 6.5% of 
dose.  In rats, 2.6% of the dose was recovered in bile and 0.16% in urine.  In dogs, 1.5% of the 
dose was recovered in urine.  
2.2.6 Potential for drug interactions:  Infigratinib is likely subject to a major intestinal metabolic 
first-pass effect via cytochrome P450 3A (CYP3A), and consequently, concomitant use with 
CYP3A inhibitors or inducers is expected to have clinical implications.  Accordingly, strong 
inhibitors or inducers or CYP3A4, as well as narrow therapeutic index substrates of CYP3A4, 
are prohibited on this study (Appendix A);  moderate inhibitors or inducers of CYP3A4, as well 
as sensitive CYP3A substrates, are to be used with caution on this study (Appendix B).  
2.2.7 Safety in animal studies:  Repeated-dose toxicity studies were performed in rat and dog 
and are summarized below:  
 
Infigratinib increased serum fibroblast growth factor 23 (FGF23) and serum calcium 
and/or phosphorus, associated with ectopic mineralization (mostly lungs and kidneys) 
and bone growth plate thickening and increased trabecular bone.  Generally these 
changes were either reversible or showed a trend toward reversibility.  FGF23 is 
secreted by osteocytes and acts on the kidney to decrease reabsorption and increase 
excretion of phosphorus; it is hypothesized that inhibition of the FGF23/FGFR pathway 
leads to the observed phosphorus elevation with infigratinib.  
 
Vasculopathy was observed in rat studies at higher dose levels; in dog studies, this was 
observed only in the gallbladder.  
 
In rats and dogs increases in alanine aminotransferase, aspartate aminotransferase, 
and/or decreases in glucose were noted.  These changes were either without correlative 
histopathological findings or (in dogs at high doses) with minimal liver cell necrosis as 
well as bile ducts hypertrophy/hyperplasia.  


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 
There was an accumulation of foam cell aggregates in the lung.  
 
Decreases in reticulocyte, platelet, total white blood cells, neutrophils, and lymphocytes 
as well as bone marrow hypocellularity were noted at higher doses.  
 
Cornea opacity (trend towards reversibility) as well as epithelial thinning for the tongue 
and nasal cavity (reversible) as well as incisors (not reversible) were observed.  
 
Longer hair/fur was noted starting at approximately week 8 and continuing through 
recovery.  In dogs, reversible atrophy of the sebaceous gland was seen.  
2.2.8 Efficacy in animal studies:  In vivo studies in mice and rats have shown that significant 
tumor growth inhibition and tumor regression can be achieved with infigratinib in a variety of 
FGFR-dependent tumor xenograft models, at well tolerated doses when given orally once per 
day.  
2.2.9 Safety in humans:  Infigratinib has been evaluated in cancer patients in two phase 1 
studies in patients with advanced solid malignancies (NCT01697605 and NCT01004224) and 
three phase 2 studies (NCT01975701 in glioblastoma; NCT02150967 in cholangiocarcinoma, 
and NCT02160041 in solid tumors and/or hematologic malignancies).  It has also been 
evaluated in combination with the PI3K alpha specific inhibitor BYL719 in a phase 1b study 
(NCT01928459), a combination no longer being pursued.  Approximately 650 subjects (healthy 
adult volunteers and adult patients with malignancies) have received infigratinib. 
Dose-limiting toxicities:  There were no DLTs reported in NCT01697605.  In NCT01004224, 
where infigratinib was given as a single agent, there was one DLT in the 100 mg cohort (out of 
6 subjects) (Grade 3 AST/ALT elevation), one DLT in the 125 mg cohort (out of 8 subjects) 
(hyperphosphatemia greater than 14 days despite adequate therapy), and 2 DLTs in the 150 mg 
cohort (out of 6 subjects) (one Grade 3 AST/ALT elevation and one Grade 1 corneal toxicity).  
The maximum tolerated dose was determined to be 125 mg daily.  The 3 weeks on / 1 week off 
schedule was implemented based on observations of the timing and duration of drug 
interruptions during Cycle 1 necessitated by episodes of hyperphosphatemia:  median time to 
drug interruption during continuous dosing was 22 days and median duration of the interruption 
was 7 days.  
Treatment-emergent adverse events:  Table 1 summarizes adverse events, regardless of 
relationship, to infigratinib as a single agent at the maximum tolerated dose of 125 mg, 
3 weeks on, 1 week off (N = 433 subjects), and Table 2 summarizes Grade 3 to 4 adverse 
events.  The on-target effects on calcium-phosphorus homeostasis result in the observed 
increases in calcium (13.4% any grade, 3.2% Grade 3-4), phosphorus (61.2% any grade, 
6.7% Grade 3 to 4), and creatinine (23.8% any grade).  These are not associated with clinical 
symptoms and in general have been mild to moderate in severity, manageable, and reversible.  
Guidelines for management of on-target hyperphosphatemia have been implemented.  
Ocular adverse events (corneal or retinal) occur in about 50% of subjects, but in general are 
mild to moderate in severity and reversible: for example, Grade 1 to 2 dry eye was reported in 
21.5% and Grade 1 to 2 blurry vision in 9.9%.  Grade 3 ocular events occurred in 3% of 
subjects; no Grade 4 ocular events have been reported.  Grade 3 adverse events of cataract 
(N = 3, 0.7%), visual impairment (N = 2, 0.5%), and keratitis (N = 2, 0.5%) were the events that 


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occurred in more than one subject; others were reported once.  Adverse events of 
blurred vision, visual impairment, and keratitis led to study drug discontinuation for N = 2, 0.5% 
subjects each.  Since the cornea and retina were identified from preclinical safety studies as a 
potential target organ of interest, protocol-mandated ophthalmologic examinations have been 
performed routinely and frequently throughout studies.  
Subjects have been monitored for potential QT prolongation: N = 3 (0.7%) of subjects have had 
a new QTc value > 500 msec, N = 4 (1.0%) have had a QTcF change of > 60 msec, and 
N = 63 (15.0%) have had a QTcF change > 30 and ≤ 60 msec.  None of these events was 
considered serious nor led to treatment withdrawal or dose reduction/interruption.  Subjects 
have also been monitored for potential decrease in ventricular ejection fraction by 
echocardiogram or multi-gated acquisition.  N = 6 (1.4%) of subjects had a Grade 2 abnormality 
(no Grade 3-4 events), which did not lead to study drug discontinuation.  
Other notable adverse events include stomatitis (34.9%) and alopecia (26.8%).  


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Table 1: Adverse events occurring in ≥ 10% of adult oncology subjects  
treated with infigratinib monotherapy 
 


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Table 2:  Grade 3 or 4 adverse events occurring in ≥ 1.0% of  
adult oncology subjects treated with infigratinib monotherapy 
 
Serious adverse events:  Serious adverse events (SAEs) to single-agent infigratinib are 
summarized in Table 3.  The most common SAEs reported (approximately 2%) were pyrexia, 
dyspnea, general physical health deterioration, sepsis, vomiting, abdominal pain, anemia, 
hypercalcemia, and pneumonia.  Most of the SAEs would be expected for oncology subjects 
and for the indications under study.  


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Table 3:  SAEs occurring in 0.5% of adult oncology subjects  
treated with infigratinib monotherapy 
 
Deaths:  Of the 433 subjects treated with infigratinib monotherapy, N = 45 (10.4%) have died 
on-treatment.  Most deaths were deemed related to study indication / disease progression.  
One death due to cardiac arrest and 1 death due to intestinal ischemia were considered to be 
related to study drug.  


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2.2.10 Efficacy in humans:  In NCT01004224, a phase 1 dose-escalation study, 4 of 36 subjects 
with non-small cell lung cancer and 3 of 8 subjects with urothelial carcinoma achieved partial 
response (Figure 1). 13  Of the 26 subjects with metastatic breast cancer (21 with FGFR1 
amplification), 4 had reduced tumor burden but did not achieve partial response (3 with FGFR1 
amplification). 13  In addition, of the 37 additional subjects with urothelial carcinoma, 
12 achieved partial response and 1 achieved complete response (CR). 14  In NCT02150967, 
15 of 59 subjects achieved partial response.  
  
Figure 1.  Waterfall plots of best change from baseline in the size of target lesions for patients treated at 
least 100 mg infigratinib.  From Nogova et al (2016) JCO.  
Subsequently, in a phase 2 study of infigratinib 125 mg orally daily 3 weeks on / 1 week off in 
N = 67 subjects with metastatic urothelial carcinoma with FGFR3 alterations, an overall 
response rate of 25.4% and a disease control rate of 64.2% was observed. 14  In another 
phase 2 study of infigratinib 125 mg orally daily 3 weeks on / 1 week off in N = 61 subjects with 
advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR 
alterations, an overall response rate of 14.8% and a disease control rate of 75.4% was 
observed. 15  
2.2.11 Additional information:  Further details are available in the Investigator’s Brochure, which 
is included with the IRB submission.  This study will be conducted under IND 147595 
(pre-assigned).  Infigratinib was approved by FDA as Truseltiq pursuant the Accelerated 
Approval regulations on 28 May 2021 for the indication of previously-treated, unresectable, 
locally-advanced or metastatic cholangiocarcinoma with a fibroblast growth factor 
receptor 2 (FGFR2) fusion or other rearrangement, in adults.  


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2.3 
Rationale  
2.3.1 Rationale for combination of infigratinib with endocrine therapy:  An analysis of 
1,980 subjects with molecular data and 20 years of follow-up was recently performed.  In this 
work, it was found that tumors classifying as integrative subtype 2 (characterized by the 
11q13/14 amplification including FGF3/4/19 and accounting for approximately 5% of all 
HR+/HER2- breast tumors) or integrative subtype 6 (characterized by the 8p12 amplification 
including FGFR1 and account for approximately 5% of all HR+/HER2- tumors) exhibit an 
exceedingly high risk of distant relapse up to 20 years post-diagnosis (median 42 to 55%). 2  
Substantial improvement in progression-free survival has been seen in HR+/HER2- metastatic 
breast cancer with the addition of CDK4/6 inhibition to endocrine therapy, 4-9 but virtually all 
tumors will eventually progress, leading to breast cancer-related death.  The current treatment 
paradigm of metastatic HR+/HER2- FGF(R)-altered breast cancer does not include inhibition of 
the FGFR pathway.  As a single agent in humans, infigratinib has shown some antitumor activity 
in pre-treated metastatic breast cancers with FGFR1 amplification, but not achieving the level of 
a partial response (Figure 1). 13  Breast tumors with FGF(R) pathway alterations are in urgent 
need of more effective therapies, and we propose that combining infigratinib with endocrine 
therapy could achieve this goal.  
Accumulating preclinical and clinical data suggests that FGFR1 amplification may drive 
endocrine therapy resistance in breast cancer. 16,17  For example, FGFR1-amplified cell lines 
showed resistance to 4-hydroxytamoxifen, which was reversed by RNA silencing of FGFR1. 18  
ER+/FGFR1-amplified tumors treated with letrozole prior to surgery did not show decreases in 
proliferation as measured by Ki67 as is typically seen in sensitive tumors, and this primary 
resistance to aromatase inhibition appeared to be mediated by an upregulation of FGFR1 and 
FGF ligand expression allowing persistent activation of estrogen response. 17  Similarly, another 
study found that time to progression on first-line endocrine therapy was shorter in 
FGFR1-amplified ER+ metastatic breast cancers than in ER+ metastatic breast cancers that 
were not FGFR1-amplified, a difference not seen for first-line chemotherapy. 19  Combining 
lucitanib (a non-selective FGFR inhibitor) with fulvestrant improved growth inhibition of 
ER+/FGFR1-amplified cell lines and patient-derived xenografts. 17  Another study validated the 
finding of intrinsic endocrine therapy resistance in ER+/FGFR1-amplified primary tumors, and 
also reported a similar phenomenon for tumors with CCND1/FGF3/4/19 amplification. 20  
In sum, these data provide a rationale for combining infigratinib with endocrine therapy may 
overcome the intrinsic endocrine therapy resistance of ER+/FGFR1-amplified or 
ER+/CCND1/FGF3/4/19-amplified tumors.  For those subjects whose tumors have 
demonstrated primary or secondary resistance to endocrine therapy (ie, by progression on an 
aromatase inhibitor or fulvestrant), adding FGFR inhibition may allow these tumors to sensitize 
to endocrine therapy.  
Notably, FGFR inhibition in combination with fulvestrant has been attempted previously in 
breast cancer, in a phase 2, randomized, placebo-controlled study of dovitinib in combination 
with fulvestrant in postmenopausal subjects with hormone receptor-positive, HER2-negative 


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breast cancer that progressed during or after prior endocrine therapy. 21  This study of 
N = 97 subjects showed median progression-free survival of 5.5 months in the dovitinib arm and 
5.5 months in the placebo arm (HR 0.68) in the overall cohort.  Findings were not significantly 
different in the FGF pathway-amplified subgroup (N = 31):  median PFS 10.9 months in the 
dovitinib arm and 5.5 months in the placebo arm (HR 0.64).  However, dovitinib is one of several 
non-selective multi-kinase inhibitors with greater impact on VEGFR than FGFR (another 
example is lucitinib), and subsequent studies have strongly suggested that these multi-kinase 
inhibitors may not effectively inhibit the FGFR pathway in subjects. 22,23  The efficacy of FGFR 
inhibition is most established thus far in FGFR-altered (most commonly FGFR3-mutated) 
advanced urothelial carcinoma, the setting for which the selective FGFR inhibitor erdafitinib 
received FDA approval as Balversa on 12 April 2019 (Accelerated Approval).  Dovitinib was 
studied in this setting as well in a phase 2 study that treated N = 12 FGFR3-mutated and N = 31 
FGFR3-wild-type advanced urothelial cancer subjects. 24  In this study, the ORR in the 
FGFR3-mutated subgroup was 0% (3.2% in the wild-type subgroup).  Also, and importantly, no 
hyperphosphatemia was observed in these subjects, nor in other subjects who have been 
treated with dovitinib.  Hyperphosphatemia is a key on-target effect of FGFR inhibition and its 
absence with dovitinib and other multi-kinase inhibitors suggests poor FGFR inhibition. 22,23  
Conversely, in the phase 2 study of FGFR-altered advanced urothelial cancer that led to 
erdafitinib’s approval, the ORR was 32% (28 of 87 subjects) with 69% experiencing 
hyperphosphatemia, 25 and in a similar phase 2 study of infigratinib, the ORR was 25% 
(16 of 67 subjects) with 50% experiencing hyperphosphatemia. 14  Dovitinib is no longer widely 
considered an effective FGFR inhibitor, 22,23 while the new generation of selective FGFR 
inhibitors are rapidly gaining ground in establishing their efficacy in FGFR-altered 
cancers. 14,15,25  We therefore believe it is time to assess the hypothesis that selective FGFR 
inhibition in combination with endocrine therapy may have a benefit for FGFR-altered hormone 
receptor-positive advanced breast cancer patients.  
2.3.2 Comparison to other active trials: To our knowledge, there are 2 active clinical trials 
examining FGFR inhibition in combination with endocrine therapy in metastatic breast cancer, 
one of which also adds CDK4/6 inhibition.  NCT04024436 opened October 2019 and is a 
nonrandomized phase 2 study will administer TAS-120 (Taiho) in combination with fulvestrant to 
4 cohorts, 3 of which will have an FGFR2 amplification and 1 of which will have a high-level 
(ratio to centromere ≥ 5) FGFR1 amplification.  Neither of these studies will examine the efficacy 
of FGFR inhibition in combination with endocrine therapy in tumors harboring amplification of 
the ligand (FGF3; integrative subtype 2).  The hypothesis driving the present trial is that the 
unique drivers identified via integrative subtyping (a subset of tumors with FGFR1 amplification 
classifying as integrative subtype 6; and a subset of tumors with FGF3 amplification classifying 
as integrative subtype 2) will be uniquely sensitive to FGFR inhibition.  
2.3.3 Rationale for dose of tamoxifen:  The dose and schedule selected for tamoxifen 
(20 mg/day by mouth continuously) is FDA-approved for the treatment of ER+ metastatic breast 
cancer.  


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2.4 
Screening Tumor Sequencing Assays  
Potential subjects will be eligible if their tumor classifies as integrative cluster 2 (IC2) or 6 (IC6) 
based on the results of the FoundationOne (F1CDx) FDA-approved assay.  There are 
11 validated integrative subtypes or clusters of breast cancer, defined initially from the 
METABRIC cohort based on the integration of genomic copy number alterations and 
transcriptional profiles. 3  Our recent study examining 20 years of clinical follow-up from 
1,980 subjects in the initial METABRIC cohort revealed substantial variability in the risk of 
relapse amongst HR+/HER2- subjects. 2  In particular, integrative subtypes 1, 2, 6, and 9 
exhibited exceedingly high (median 42 to 55%) risk of distant relapse up to 20 years 
post-diagnosis.  Each of these integrative subtypes is characterized by distinct copy number 
amplification events and concomitant over-expression of candidate driver genes:  integrative 
subtype 2 has the FGF3/FGF4/FGF19, CCND1 (11q13/14) amplification and integrative 
subtype 6 has the FGFR1 (8p12) amplification.  While these characteristic amplifications are 
almost universally present within tumors classifying as the relevant integrative subtype, the 
converse is not true:  only approximately one-quarter of ER+/HER2- tumors that carry the 
CCND1/FGF3/4/19 amplification classify as integrative subtype 2, and approximately one-half of 
ER+/HER2- tumors that carry the FGFR1 amplification classify as integrative subtype 6. It is 
plausible that these amplifications may be passenger events rather than driver events in the 
tumors that do not classify as the relevant integrative subtypes.  Using additional information 
from targeted sequencing panels can improve the accuracy of integrative cluster classification, 
and we hypothesize better delineate in which tumors the FGFR pathway is the oncogenic driver 
than the simple presence of the amplification. 2,3  Thus, subjects will be eligible if their tumor’s 
F1CDx results are consistent with integrative cluster 2 or 6, per the classifier.  The classifier was 
developed to predict integrative cluster classification from the copy number values and 
mutational status of the genes on the F1CDx panel in two large cohorts of breast tumors, 
METABRIC 3 and The Cancer Genome Atlas 28.  This classifier will be applied to the integer 
copy number values and gene mutation calls generated by the F1CDx assay and analysis. 
2.5 
Study Design  
 
The primary purpose for this study is treatment.  The protocol is designed to evaluate 
one or more interventions for treating a disease, syndrome, or condition.  
 
The interventional model is Sequential.  
 
The number of intervention arms is up to 3.  
 
The study will be not be masked (not blinded).  
 
The study will be not be randomized.  
This is a phase 1b study evaluating the safety and tolerability of infigratinib.  Cohort 1 will utilize 
the combination of tamoxifen and infigratinib.  We anticipate that this combination may play a 
role in the future development of infigratinib for hormone receptor-positive breast cancer, 
necessitating the establishment of their safety.  For example, tamoxifen and infigratinib might be 
used in the early-stage, (neo)adjuvant setting as well as the late-stage, metastatic setting. 


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In Cohort 1, up to 3 dose levels of infigratinib may be evaluated (125 mg;  100 mg;  and 75 mg) 
in combination with tamoxifen.  This pilot study is a necessary step for the future development of 
infigratinib in combination with tamoxifen and will serve as a safety run-in evaluation for a 
follow-up study.  For this cohort, a 3 + 3 design will be employed starting at 100 mg, and 
allowing subjects who start at 100 mg to escalate to 125 mg (see Section 12.4). 
2.6 
Correlative Studies Background 
2.6.1 Organoid cultures:  Three-dimensional organoid cultures established from viable tumor 
cells have the potential to re-capitulate in vitro subject- and tumor-specific phenotypes, enabling 
the study of drug response and tumor evolution in the lab. 32-34  Tumor organoid cultures can be 
established as a renewable source of tissue for in vitro and in vivo experimentation; they are 
amenable to high-throughput drug screens and complementing xenograft-based approaches.  
Organoid culture can be used to evaluate the efficacy of novel therapeutic agents in specific 
genetic contexts.  It is planned to establish organoids from tumors in this study, classifying as 
integrative subtypes 2 and 6, allowing testing of novel drug combinations to improve response 
and overcome resistance to FGFR inhibition in these high-risk subgroups.  Furthermore, as 
these organoids will be treated in vitro with the same agents that the study subjects from whose 
tumors they were derived will be, we will be able to compare response between the in vitro and 
subjects.  We will also be able to compare the genomic alterations that arise with treatment in 
subjects (Section 2.6.2) with those that arise with treatment in the organoids.  These 
experiments may inform our understanding of genomic determinants of sensitivity and 
resistance to FGFR inhibition, as well as the optimal combinations of therapies to produce 
response in FGFR-altered breast tumors.  
2.6.2 Cell-free DNA analyses:  Cell-free DNA is believed to be representative of the 
heterogeneity present even in micro-metastatic lesions. 35  Thus, it may better capture the 
spectrum of subclonal populations with the potential to grow in response to therapy than serial 
tumor biopsies.  Furthermore, it has been shown that cell-free DNA sequencing can detect and 
characterize clonal dynamics in metastatic breast cancer. 36-38  It is planned to collect blood from 
subjects prior to initiation of study drug, after the first 2 weeks of therapy, and at time of 
confirmed progression.  The blood samples will be separated into plasma and buffy coat and 
banked.  Sequencing (eg, whole-exome or whole-genome) of the cell-free DNA extracted from 
these banked plasma samples will allow us to identify novel mutations or copy number changes 
that appear at time of progression in subjects who initially responded, as well as to compare 
baseline genomic changes between responders and non-responders.  The banked buffy coat 
samples will allow us to identify somatic variants that act as driver mutations and compare them 
to a matched normal sample through tumor-normal whole-genome sequencing.  Furthermore, 
we can cross-reference these findings with genomic findings in the organoid models 
(Section 2.6.1).  These analyses may allow us to identify genetic mechanisms of resistance to 
the study drug and/or endocrine therapy.  
2.6.3 Proteomic profiling:  Proteomic changes may be examined in tumor cells and the 
surrounding microenvironment in situ to delineate compensatory signaling pathways and 
mechanisms of response/resistance to the evaluated targeted agents.  Paired pre- and 


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post-treatment tissue samples from the trial may be profiled on the Nanostring GEOMx Digital 
Spatial Profiling (DSP) platform (Research Use Only) 39,40 or with mutiplexed ion beam 
imaging (MIBI). 41-43  There is growing evidence that functional heterogeneity in the tumor and 
microenvironment contribute to treatment response, highlighting the importance of spatially 
resolved approaches such as DSP.  DSP enables geographic and phenotypic selection of tissue 
regions – for example, those that are enriched for pancytokeratin-positive tumor cells.  
Molecular changes observed with treatment may inform intelligent combinations of therapy in 
the future to overcome primary resistance or enhance treatment response.  
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES  
Inclusion and Exclusion Criteria are provided on Participant Eligibility Checklist following.  This 
document may be extracted from this document for use in screening potential subjects.  
The Participant Eligibility Checklist in the following subsection must be completed in its entirety 
for each subject prior to registration.  The Participant Eligibility Checklist may be extracted from 
this document for use in screening potential subjects.  The completed, signed, and dated 
checklist must be retained in the subject’s study file, and the study’s Regulatory Binder.  
Screening results will be collectively documented on the Study Participant Log.  
Pursuant to Stanford Medicine SOP “Confirmation of Participant Eligibility in Clinical Trials,” the 
treating Physician (investigator);  the Study Coordinator;  and a third reviewer from the study 
team (eg, investigator or back-up study coordinator) will verify that the subject’s eligibility is 
accurate; complete; and legible in source records.  A description of the eligibility verification 
process should be included in the EPIC or other Electronic Medical Record progress note.  
 


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Participant Eligibility Checklist  
I. 
Protocol Information  
Protocol Title: 
A Phase 1B Study of Infigratinib in Combination with Tamoxifen in 
Hormone Receptor-Positive, HER2-Negative, FGFR-Altered Advanced 
Breast Cancer 
eProtocol number: 
OnCore number: 
IRB-53650  
BRS0113  
Principal Investigator 
[per 21CFR§312.3(b)]: 
Jennifer L Caswell-Jin, MD 
II. 
Subject Information  
Subject name / Unique ID: 
/ 
Gender  
  Male   
 Female   
3.1 
Inclusion Criteria 
Prospective Participant Must MATCH  
ALL these Inclusion Criteria to be Eligible 
Yes No 
Supporting 
Documentation * 
1. History of biopsy-proven ER-positive and/or 
PR-positive, HER2-negative breast cancer and 
radiographic evidence of metastatic disease, or 
locally recurrent unresectable disease.  ER-positivity 
and PR-positivity are defined as ≥ 1% cells staining 
positive by immunohistochemistry.  HER2-negativity 
is defined by IHC or FISH, per ASCO-CAP 2018 
guidelines 
 
 
 
2. Cancer subtype indicative of alterations to the 
fibroblast growth factor ligand or receptor 
(FGF/FGFR alteration):  Predicted integrative 
(IntClust) subtype classification of IC2 or IC6 
according classifier on targeted sequencing data 
from FoundationOne.  
 
 
 


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Prospective Participant Must MATCH  
ALL these Inclusion Criteria to be Eligible 
Yes No 
Supporting 
Documentation * 
3. Evaluable or measurable disease. 
Cohort 1 only:  Evaluable or measurable disease, 
as defined by RECIST v1.1.  Bone-only disease is 
acceptable. 
 
 
 
4. ≥ 18 years old  
 
 
 
5. Eastern Cooperative Oncology Group (ECOG) 
performance status 0 to 2 
 
 
 
6. Prior cancer therapy (except for endocrine therapy, 
denosumab, or bisphosphonates) must be 
discontinued for 2 weeks prior to initiation of study 
drugs.  Recovery from adverse events of previous 
cancer therapies to baseline or Grade 1 except for 
alopecia or stable Grade 2 neuropathy.  
Radiotherapy must also be completed at least 
2 weeks prior to initiation of study drugs  
 
 
 
7. Absolute neutrophil count (ANC) ≥ 1,000/mm3  
 
 
 
8. Platelets ≥ 75,000/mm3  
 
 
 
9. Hemoglobin ≥ 9.0 g/dL 
 
 
 
10. Total bilirubin ≤ 1.8 mg/dL (unless documented 
Gilbert’s disease) 
 
 
 
11. Aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) < 90 U/L  
 
 
 
12. Estimated glomerular filtration rate (GFR) 
≥ 45 mL/min  
 
 
 
13. Phosphorus between 2.5 and 4.5 mg/dL, inclusive  
 
 
 
14. Total corrected (for albumin) serum calcium 
between 8.5 and 10.5 mg/dL, inclusive 
 
 
 
15. Amylase < 200 U/L 
 
 
 
16. Lipase < 120 U/L 
 
 
 
17. Ability to understand and the willingness to sign a 
written informed consent document 
 
 
 


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Prospective Participant Must MATCH  
ALL these Inclusion Criteria to be Eligible 
Yes No 
Supporting 
Documentation * 
18. Agrees to take sevelamer, if indicated, and has no 
contraindications to use of this medication (that is: 
known hypersensitivity to sevelamer or component 
of the formulation; bowel obstruction; active bowel 
mucosal injury such as ulcerative colitis or 
gastrointestinal bleeding). 
 
 
 
19. Agrees to follow low-phosphate diet, if indicated  
 
 
 
20. Able to swallow and retain oral medication 
 
 
 
21. Women must be postmenopausal, defined as 
(at least one of):   
• ≥ 60 years of age; 
• amenorrhea for at least 24 months; 
• amenorrhea for at least 12 months with  
  serum estradiol < 20 pg/mL; 
• prior bilateral oophorectomy;  
  OR  
• treatment with a luteinizing hormone (LH)- 
  releasing hormone agonist (such as  
  goserelin acetate or leuprolide acetate) initiated  
  at least 28 days prior to study enrollment.   
 
 
 
22. Women being treated with a LH-releasing agonist 
but who are otherwise of childbearing potential (did 
not undergo total hysterectomy or bilateral tubal 
ligation at least 6 weeks before first dose of study 
drug) must have a negative pregnancy test within 
7 days of the first dose of study drug. 
 
 
 
23. Women who are being treated with an LH-releasing 
agonist but are otherwise of childbearing potential 
must agree to use barrier contraception or an 
intrauterine device while taking study drug and for 
3 months following their last dose of study drug.  
Alternatively, total abstinence is acceptable if 
preferred by the subject.  
 
 
 


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Prospective Participant Must MATCH  
ALL these Inclusion Criteria to be Eligible 
Yes No 
Supporting 
Documentation * 
24. Sexually-active men must agree to use a condom 
during intercourse while taking drug and for 
3 months after the last dose of the study drug and 
should not father a child during this period.  
A condom is required to be used also by 
vasectomized men as well as during intercourse 
with a male partner to prevent delivery of the drug 
via seminal fluid.  
 
 
 
3.2 
Exclusion Criteria 
Prospective Participants Must NOT Match  
ANY of These Exclusion Criteria  
Yes No 
Supporting 
Documentation * 
1. History of another primary malignancy within 3 years 
except adequately treated in situ carcinoma of the 
cervix or non-melanoma carcinoma of the skin or 
any other curatively treated malignancy that is not 
expected to require treatment for recurrence during 
the course of the study.   
 
 
 
2. Neurologic symptoms related to central nervous 
system metastases requiring increasing doses of 
corticosteroids.  Note that subjects with central 
nervous system metastases ARE eligible if they are 
on a stable corticosteroid dose for at least 2 weeks 
preceding study entry. 
 
 
 
3. Current evidence of corneal or retinal 
disorder/keratopathy including, but not limited to, 
bullous/band keratopathy, corneal abrasion, 
inflammation/ulceration, keratoconjunctivitis, 
confirmed by ophthalmologic examination.  Subjects 
with asymptomatic ophthalmologic conditions 
assessed by the investigator to pose minimal risk for 
study participation may be enrolled in the study.   
 
 
 


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Prospective Participants Must NOT Match  
ANY of These Exclusion Criteria  
Yes No 
Supporting 
Documentation * 
4. Current evidence of extensive tissue calcification 
including, but not limited to, the soft tissue, kidneys, 
intestine, myocardium, and lung with the exception 
of calcified lymph nodes, minor pulmonary 
parenchymal calcifications, and asymptomatic 
coronary calcification.   
 
 
 
5. Impairment of gastrointestinal (GI) function or GI 
disease that may significantly alter the absorption of 
oral infigratinib (eg, ulcerative diseases, 
uncontrolled nausea, vomiting, diarrhea, 
malabsorption syndrome, small bowel resection). 
 
 
 
6. Current evidence of endocrine alterations of 
calcium/phosphate homeostasis, eg, parathyroid 
disorders, history of parathyroidectomy, tumor lysis, 
or tumoral calcinosis. 
 
 
  
7. Currently receiving or planning during study 
participation to receive treatment with agents that 
are known strong inducers or inhibitors of CYP3A4 
and medications which increase serum phosphorus 
and/or calcium concentration.  Subjects are not 
permitted to receive enzyme-inducing anti-epileptic 
drugs, including carbamazepine, phenytoin, 
phenobarbital, and primidone.  See Appendix A for 
a list of prohibited concomitant medications and 
supplements. 
 
 
 
8. Has consumed grapefruit, grapefruit juice, grapefruit 
hybrids, pomegranates, star fruits, pomelos, Seville 
oranges, or products containing juice of these fruits 
within 7 days prior to first dose of study drug. 
 
 
 
9. Have used amiodarone within 90 days prior to first 
dose of study drug. 
 
 
 
10. Has used medications known to prolong the 
QT interval and/or are associated with a risk of 
Torsades de Pointes (TdP) 7 days prior to first dose 
of study drug.  See Appendix A for a list of 
prohibited concomitant medications and 
supplements. 
 
 
 


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Prospective Participants Must NOT Match  
ANY of These Exclusion Criteria  
Yes No 
Supporting 
Documentation * 
11. Has used calcium or vitamin D within 3 days prior to 
first dose of study drug.  Calcium supplementation 
may subsequently be used as clinically indicated 
(for hypocalcemia) on study. 
 
 
 
12. Have clinically significant cardiac disease including 
any of the following:  
a. Congestive heart failure requiring treatment 
(New York Heart Association Grade ≥ 2), left 
ventricular ejection fraction (LVEF) < 50% or 
local lower limit of normal as determined by 
multiple gated acquisition (MUGA) scan or 
echocardiogram (ECHO), or uncontrolled 
hypertension (refer to the European Society of 
Cardiology and European Society of 
Hypertension guidelines [Williams et al., 2018])  
b. Presence of Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0 Grade ≥ 2 
ventricular arrhythmias, atrial fibrillation, 
bradycardia, or conduction abnormality  
c. Unstable angina pectoris or acute myocardial 
infarction ≤ 3 months prior to first dose of study 
drug  
d. Corrected QT interval-Fredericia (QTcF) > 470 
msec (males and females).  Note:  If the QTcF is 
> 470 msec in the first electrocardiogram (ECG), 
a total of 3 ECGs separated by at least 5 
minutes should be performed.  If the average of 
these 3 consecutive results for QTcF is ≤ 470 
msec, the subject meets eligibility in this regard.  
e. Known history of congenital long QT syndrome 
 
 
 
13. Have had a recent (≤ 3 months) transient ischemic 
attack or stroke.   
 
 
 
14. Pregnant or nursing  
 
 
 
* All subject files must include supporting documentation to confirm subject eligibility.  The 
method of confirmation can include, but is not limited to, laboratory test results, radiology test 
results, subject self-report, and medical record review.  


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V. 
Statement of Eligibility  
By signing this form of this trial I verify that this subject is:  
 eligible / 
 ineligible  
for participation in the study.  This study is approved by the Stanford Cancer Institute Scientific 
Review Committee, the IRB of record, and has finalized financial and contractual agreements as 
required by Stanford School of Medicine’s Research Management Group.   
Study Coordinator printed name: 
Date:  
Signature: 
 
Investigator printed name: 
Date:  
Signature: 
 
Triple-check reviewer printed name: 
Date:  
Signature: 
 


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3.3 
Informed Consent Process  
All subjects must be provided a consent form describing the study with sufficient information for 
subjects to make an informed decision regarding their participation.  Subjects must sign the IRB 
approved informed consent prior to participation in any study specific procedure.  The subject 
must receive a copy of the signed and dated consent document.  The original signed copy of the 
consent document must be retained in the medical record or research file.  
3.4 
Study Timeline  
Primary Completion:  
It is anticipated that the study will reach primary completion (30 days after final subject 
completes treatment with study agents) 24 months from the time the study opens to accrual.  
Study Completion:  
It is anticipated that the study will reach study completion (final date on which data are 
collected) 36 months from the time the study opens to accrual.  
4. 
TREATMENT PLAN  
Potential subjects who preliminarily meet inclusion criteria and exclusion criteria as determined 
by study staff (for example, the investigator or clinical research coordinator) will meet with study 
staff to review the study and informed consent in detail.  At this time, inclusion and exclusion 
criteria will be confirmed with the subjects and treating clinicians as necessary.  
All eligible subjects (meeting criteria described in Section 3) will receive the drug combination of 
infigratinib with tamoxifen.  Once a dose level for infigratinib is determined, Cohort 1 will close.  
All subjects in whom a research biopsy of a disease site is deemed feasible and safe by the 
investigator will be required to undergo a biopsy to donate 4 to 8 cores of tumor tissue before 
and on-treatment to be used for research purposes, including genomic/transcriptomic/proteomic 
analysis and organoid culture derivation as described in Section 2.6.  The on-treatment biopsy 
is recommended to occur on Day 15 of treatment, but any time on treatment is acceptable.  
Tissue will be transported to the Curtis lab for processing and analysis.  Subjects who require a 
tumor biopsy for eligibility assessment will undergo the collection of tissue cores for research 
simultaneously, whenever possible.  Archival tumor tissue, including stored at Stanford 
University and at other institutions, may be obtained for use for tissue correlative studies as 
well.  Only tissue not needed for diagnostic purposes will be used for research.  
Subjects in Cohort 1 will receive tamoxifen 20 mg orally continuously starting on Day 1 and will 
additionally receive infigratinib orally daily 3 weeks on, 1 week off (28-day cycle) at the dose 
level dictated by study protocol (125 mg, 100 mg, or 75 mg).  
Subjects will continue receiving cycles as above until 18 months on treatment, progression, or 
unacceptable toxicity (or other reasons outlined in Section 4.3).  If toxicity is deemed per the 
investigator to be related to endocrine therapy (tamoxifen) and not infigratinib, subjects will be 
given the option of continuing infigratinib only (without endocrine therapy) until progression.   


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Details on study procedures during Screening, Treatment, and Post-Treatment are provided in 
the Study Calendar and footnotes (Section 9).  
4.1 
General Concomitant Medication and Supportive Care Guidelines  
4.1.1 Concomitant Medication 
Administration of other anticancer therapies within 2 weeks of enrollment, except ongoing 
administration of a bisphosphonate drug or denosumab as treatment for bone metastasis or 
ongoing administration of a luteinizing hormone-releasing hormone agonist (such as goserelin 
acetate or leuprolide acetate) or other endocrine therapy, is prohibited.  
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions providing 
the lesions were known at the time of study entry and the investigator clearly indicates that the 
need for palliative radiotherapy is not indicative of disease progression.  In view of the current 
lack of data about the interaction of infigratinib with radiotherapy, infigratinib treatment should be 
interrupted during palliative radiotherapy, resuming infigratinib treatment after recovery to 
≤ Grade 1 radiotherapy-related toxicity.  
Details for specific medications prohibited while on study are provided in Appendix A.  The 
rationale for the restricted medications is provided below.  
Strong inhibitors of CYP3A4 such as the ones listed in Appendix A are prohibited because 
infigratinib is a likely substrate of this isoenzyme.  
Strong inducers of CYP3A4 are prohibited because their usage may decrease the exposure of 
infigratinib.  Therefore, agents such as those listed in Appendix A are prohibited.  Please note 
that the list may not be exhaustive.  
Subjects must also avoid the consumption of grapefruits;  grapefruit juice;  grapefruit hybrids;  
pomegranates;  star fruits;  pomelos;  Seville oranges;  or juice within 7 days prior to the first 
dose of infigratinib and throughout the treatment period due to a potential CYP3A4 interaction 
with study drug.  
Medications that increase the serum levels of phosphorus and/or calcium are prohibited.  
Preliminary clinical data have shown that infigratinib has no effect on cardiac conduction or ECG 
intervals (See current version of the infigratinib Investigator’s Brochure).  However, medications 
that are known to prolong the QT/QTc interval or induce TdP (risk of TdP/QT prolongation) are 
prohibited.  List of these medications is given in Appendix A.  Please note that the list might not 
be comprehensive.  
Medications that are allowed but should be administered with caution are provided in 
Appendix B.  The rationale for these medications is provided below.  
Infigratinib is characterized by pH-dependent solubility, and therefore, medicinal products that 
alter the pH of the upper GI tract may alter the solubility of infigratinib, and limit bioavailability.  
These agents include, but are not limited to, proton pump inhibitors (eg, omeprazole), 
H2-antagonists (eg, ranitidine) and antacids.  If possible, proton pump inhibitors should be 
avoided due to their long PD effect and replaced with H2-antagonists or antacids.  Study drug 
should be taken ≥ 2 hours before or 10 hours after dosing with a gastric protection agent.  


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Infigratinib is a substrate of CYP3A4.  Therefore, moderate inhibitors and inducers should be 
used with caution if an alternative is not available.  If anticoagulation is required, heparin and/or 
low-molecular-weight heparins or direct thrombin inhibitors and/or Factor Xa inhibitors that are 
not metabolized by CYP3A4 (eg, dabigatran, edoxaban) are preferred.  If unavoidable, 
anticoagulants that are CYP3A4 substrates and have a narrow therapeutic index [eg, warfarin 
sodium or any other coumadin-derivative anticoagulants or certain direct thrombin inhibitors 
(eg, argatroban or Factor Xa inhibitors, eg, rivaroxaban)] should be used with caution.  
Infigratinib was shown in vitro to inhibit the drug transporter breast cancer resistance protein 
(BCRP), with an IC50 of 210 nM.  While the clinical relevance of this inhibition is unknown, drugs 
transported by BCRP should be used with caution.  
Anti-emetics are recommended as clinically appropriate at the first sign of nausea and vomiting 
or as prophylaxis to prevent emesis, along with supportive care according to clinical practice 
guidelines.  
It is recommended to avoid using drugs that are known to cause QT prolongation.  Note that 
some anti-emetics have a known risk for Torsade de Pointes, and therefore need to be used 
with caution.  See Appendix B for list of drugs that need to be used with caution.  Aprepitant 
(brand name: Emend) is both a sensitive substrate and a moderate CYP3A4 inhibitor and 
should be used with caution if an alternative is not available.  
Preliminary clinical data have shown that infigratinib has no effect on cardiac conduction or ECG 
intervals (see current version of the infigratinib Investigator’s Brochure).  However, medications 
that have the potential to prolong the QT/QTc interval or induce Torsade de Pointes (possible 
and conditional risk of TdP/QT prolongation) are allowed with caution.  Investigators at their 
discretion may co-administer such medications, but subjects should be carefully monitored.  
See Appendix B for list of drugs that need to be used with caution.  Please note that the list 
might not be comprehensive.  
Otherwise, concomitant treatment considered necessary for the subject’s well-being may be 
given at discretion of the treating physician.  All concomitant medications (including herbal 
supplements and vitamins), blood products, as well as interventions (eg, paracentesis, etc.) 
received by subjects from screening until the end of study visit will be recorded in the CRF.  
4.1.2 Supportive Care Guidelines  
Any palliative and supportive care for disease related symptoms, including any medication or 
therapy for a concurrent medical condition are permitted, except if specifically prohibited below.  
Hematopoietic Growth Factors  
Hematopoietic growth factors [eg, erythropoietin (EPO), granulocyte colony-stimulating factor 
(G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF)] and blood transfusions 
are not to be administered prophylactically or to be used to meet eligibility criteria.  However, 
these drugs may be administered as per the label of these agents or as dictated by local 
practice or guidelines established by the American Society of Clinical Oncology (ASCO), the 
National Comprehensive Cancer Network (NCCN), or other appropriate regional societies.  


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Management of Hyperphosphatemia  
Hyperphosphatemia is a recognized on-target effect of potent and selective inhibitors of the 
FGFR pathway.  
The goal of a low-phosphate diet, when one is recommended per management strategy below, 
is to restrict dietary phosphate to 600 to 800 mg/day by avoiding high-phosphate foods.  
High-phosphate foods include dairy products;  meats, nuts, and other high-protein foods;  
processed foods;  and dark colas.  In general, subjects will be instructed to liberalize their diet 
on days they are not taking infigratinib (including Days 22 to 28, and during interruption of 
infigratinib for indications other than hyperphosphatemia), unless their serum phosphorus is 
currently > 5.5 mg/dL.  Similarly, subjects who are taking sevelamer (phosphate-lowering 
medication) will be instructed to hold it on days they are not taking infigratinib (including 
Days 22 to 28, and during interruption of infigratinib for indications other than 
hyperphosphatemia), unless their serum phosphorus is currently > 5.5 mg/dL.  
Below is the recommended management strategy for hyperphosphatemia.  Section 6 also 
outlines instructions for when to interrupt and/or dose-reduce infigratinib in addition to these 
recommendations for management.  Notably, these instructions for increased monitoring of 
serum phosphorus, interruption, and dose reduction begin if serum phosphorus > 7.0 mg/dL.  
All subjects will have a serum phosphorus checked on C1D4:  
 
If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 800 mg orally 3 times daily with meals.  
 
If serum phosphorus > 7.0 mg/dL, subjects will be instructed to follow a low-phosphate 
diet and to take sevelamer 1200 mg orally 3 times daily with meals.  
All subjects will have a serum phosphorus checked on Cycle 1 Day 15:  
 
For subjects who are not currently following a low-phosphate diet or taking sevelamer:  
o If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 800 mg orally 3 times daily with meals.  
o If serum phosphorus > 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 1200 mg orally 3 times daily with meals.  
 
For subjects who are currently following a low-phosphate diet and taking sevelamer:  
o If serum phosphorus < 5.0 mg/dL, subjects will be given the option of liberalizing 
their diet or stopping the sevelamer (not both).  
o If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to increase 
the dose of sevelamer to 1200 mg orally 3 times daily with meals.  
o If serum phosphorus > 7.0 mg/dL, subjects will be instructed to increase the dose of 
sevelamer to 1600 mg orally 3 times daily with meals.  
Subsequent (after Cycle 1) management of hyperphosphatemia is as follows:  
 
For subjects who are not currently following a low-phosphate diet or taking sevelamer:  
o If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 800 mg orally 3 times daily with meals.  


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o If serum phosphorus > 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 1200 mg orally 3 times daily with meals.  
 
For subjects who are currently either following a low-phosphate diet or taking sevelamer, 
but not both:  
o If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 800 mg orally 3 times daily with meals.  
o If serum phosphorus > 7.0 mg/dL, subjects will be instructed to follow a 
low-phosphate diet and to take sevelamer 1200 mg orally 3 times daily with meals.  
 
For subjects who are currently following a low-phosphate diet and taking sevelamer 
800 mg orally 3 times daily:  
o If serum phosphorus > 5.5 and ≤ 7.0 mg/dL, subjects will be instructed to increase 
sevelamer to 1200 mg orally 3 times daily with meals.  
o If serum phosphorus > 7.0 mg/dL, subjects will be instructed to increase sevelamer 
to 1600 mg orally 3 times daily with meals.  
 
For subjects who are currently following a low-phosphate diet and taking sevelamer 
1200 mg orally 3 times daily:  
o If serum phosphorus > 5.5 mg/dL, subjects will be instructed to increase sevelamer 
to 1600 mg orally 3 times daily with meals.  
Management of Diarrhea  
Subjects should be instructed to notify their physician immediately at the first signs of poorly 
formed or loose stool or an increased frequency of bowel movements.  Administration of 
antidiarrheal/anti-motility agents is recommended at the first sign of diarrhea as initial 
management.  Some subjects may require concomitant treatment with more than one 
antidiarrheal agent.  When therapy with antidiarrheal agents does not control the diarrhea to 
tolerable levels, study drug should be temporarily interrupted or dose reduced (see Section 6).  
Management of Skin Toxicity  
Alopecia: 
Grade 1 
Consider minoxidil 5% (OTC) solution or foam once daily to scalp. 
Grade 2 
Consider minoxidil 5% (OTC) solution or foam twice daily to scalp.  Consider 
fluocinonide 0.05% solution daily to scalp. 
Palmar-plantar erythrodysesthesia syndrome:  See also Section 6 for when to interrupt or 
dose-reduce infigratinib (Grade 3). 
Grade 1 
Consider urea 20% or ammonium lactate 12% lotions twice daily to hands and feet. 
Grade 2 or 3  
 
Consider urea 20% or ammonium lactate 12% lotions twice daily to hands and feet.  
Consider fluocinonide 0.05% solution twice daily to hands and feet. 


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Paronychia:  Also see Section 6 for when to interrupt or dose-reduce infigratinib (Grade 3). 
Grade 1 to 3 
Consider cefadroxil 500 mg orally twice daily or TMP/SMX orally twice daily for 14 days.  
Soak for 15 minutes daily in white vinegar in tap water 1:1.  Obtain bacterial cultures to 
confirm sensitivity to antimicrobial.  Consult dermatology. 
Stomatitis:  Subjects should be instructed to follow good oral hygiene during therapy.  
Prophylactic dexamethasone 10 mg/5 mL swish/spit 4 times a day for the first 8 weeks can be 
considered for prevention of stomatitis, 44 for example, for subjects who have had significant 
stomatitis from previous cancer therapies.  Also see Section 6 for when to interrupt or 
dose-reduce infigratinib (Grade 3). 
Grade 1 
Consider dexamethasone elixir 0.5 mg/mL swish and spit 1 teaspoon (5 mL) 3 times 
daily. 
Grade 2 
Consider dexamethasone elixir 0.5 mg/mL swish and spit 1 teaspoon (5 mL) 3 times 
daily AND doxepin 10 mg/mL swish and spit 1 teaspoon 5 mL every 6 hours as needed 
for pain. 
Grade 3 
Consider dexamethasone elixir 0.5 mg/mL swish and spit 1 teaspoon (5 mL) 3 times 
daily AND doxepin 10 mg/mL solution swish and spit 1 teaspoon 5 mL every 6 hours as 
needed for pain.  Consider clotrimazole 10 mg lozenges four times daily. 
 
 
4.2 
Criteria for Removal from Study  
Subjects may withdraw from treatment at any time at their own request, or they may be 
withdrawn at the discretion of the investigator for safety, behavioral, or administrative reasons.  
Reasons for subject discontinuation of study treatment may include:  
 
Objective disease progression according to RECIST criteria v1.1;  
 
18 months of study drug therapy has been completed;  
 
Global deterioration of health status requiring discontinuation;  
 
Unacceptable toxicity deemed per investigator to be related to study drug, which may 
also be an adverse event;  
 
Significant protocol violation;  
 
Lost to follow-up;  
 
Subject refused further treatment;  
 
Study terminated by the investigator or sponsor;  
 
Death;  
 
Pregnancy.  


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Reasons for subject withdrawal from study follow-up may include:  
 
Completed study follow-up;  
 
Study terminated by the PI or infigratinib distributor QED Therapeutics;  
 
Lost to follow-up;  
 
Refusal for further follow-up for survival;  
 
Start of an alternative treatment regimen;  
 
Death.  
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome, if 
possible.  The investigator should inquire about the reason for withdrawal, request the subject to 
return for a final visit, and follow-up with the subject regarding any unresolved adverse events.  
The early termination final visit should include all assessments listed for the End of Treatment 
visit.  If the subject withdraws consent for disclosure of future information, no further study 
specific evaluations should be performed, and no additional data should be collected.  The 
investigators may retain and continue to use any data collected before such refusal for further 
follow-up.  
4.3 
Alternatives  
Standard treatment options for HR+/HER2- metastatic breast cancer after progression on 
endocrine therapy in combination with a CDK4/6 inhibitor include alternative endocrine therapy, 
sometimes in combination with an mTOR inhibitor (everolimus), or one of numerous 
chemotherapy options (eg, taxanes, anthracyclines, capecitabine, gemcitabine, and 
vinorelbine).  For the potential subset of subjects who not yet received a CDK4/6 inhibitor, 
standard treatment for HR+/HER2- metastatic breast cancer that has not progressed on 
endocrine therapy in combination with a CDK4/6 inhibitor is endocrine therapy in combination 
with a CDK4/6 inhibitor or, in select subjects with lower-risk disease, endocrine therapy alone.  
5. 
INVESTIGATIONAL AGENT INFORMATION  
5.1 
Investigational Agent  
For a summary, see Section 2.2.  For complete details, see Investigator’s Brochure, provided as 
a separate document.  
5.1.1 Infigratinib Dosage Form  
Hard gelatin capsules in dosage strengths from 25 mg and 100 mg (expressed as mg of 
infigratinib free-base).  Excipients will include microcrystalline cellulose, lactose monohydrate, 
HPMC2910, crospovidone, colloidal silicon dioxide, magnesium stearate, and hard gelatin 
capsule.  Infigratinib will be manufactured under Good Manufacturing Practice for investigational 
use.  


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5.1.2 Subject Instructions for Infigratinib Dosing  
Subjects should be instructed to take the daily dose of infigratinib in the morning as much as 
their schedule and appointment allow, at approximately the same time each day (24 ± 4 hour 
interval).   
Infigratinib should be taken in the fasted state at least 1 hour before or 2 hours after a meal.  It 
should be taken with a large glass of water (~250 mL) and consumed over as short a time as 
possible.  Subjects should be instructed to swallow the capsules whole and not chew them.  
Subjects in Cohort 1 should take their daily dose of tamoxifen 4 to 8 hours after their dose of 
infigratinib. 
If the subject forgets to take the scheduled dose of infigratinib in the morning, he/she should not 
take the dose more than 4 hours after the usual time and should continue treatment the next 
day.  Any doses that are missed should be skipped altogether and should not be replaced or 
made up at the next scheduled dosing.  
If vomiting occurs following dosing with infigratinib, re-dosing is not permitted the same day.  
Dosing should resume the next day.  
Infigratinib is characterized by pH-dependent solubility; therefore, medicinal products that alter 
the pH of the upper GI tract may alter the solubility of infigratinib and limit bioavailability.  These 
agents include, but are not limited to, proton pump inhibitors (eg, omeprazole), H2-antagonists 
(eg, ranitidine) and antacids.  If possible, proton pump inhibitors should be avoided due to their 
long pharmacodynamic effect and replaced with H2-antagonists or antacids.  Infigratinib should 
be taken at least 2 hours before or 10 hours after dosing with a gastric protection agent.  
Subjects must avoid the consumption of grapefruits, grapefruit juice, grapefruit hybrids, 
pomegranates, star fruits, pomelos, Seville oranges or juice within 7 days prior to the first dose 
of infigratinib and throughout the treatment period.  This is due to a potential CYP3A4 
interaction with study drug.  Normal oranges and orange juice are allowed.  
5.1.3 Packaging and Labeling  
Infigratinib capsules will be packaged in high-density polyethylene bottles with child-resistant 
closures.  Labels will include storage conditions for the drug.  
5.2 
Availability  
QED Therapeutics will supply infigratinib drug product.  
5.3 
Agent Ordering  
Infigratinib will be shipped by QED Therapeutics to the Investigational Drug Service at Stanford 
University Medical Center, shipping address:  
Stanford Health Care 
Stanford University 
Investigational Drug Service 
300 Pasteur Dr, Room H0302 
Stanford, CA, USA 94305  


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5.4 
Agent Accountability  
Infigratinib capsules will be received by designated personnel at the study site, handled and 
stored safely and properly, and kept in a secured location to which only the investigator and 
designated site personnel have access.  Upon receipt, infigratinib should be stored according to 
the instructions specified on the drug label and in the Investigator’s Brochure.  Refer to the 
Pharmacy Manual for further details.  
The investigator or designee must maintain an accurate record of the shipment and dispensing 
of infigratinib in a drug accountability log.  Subjects in the infigratinib group will be asked to 
return all used and unused bottles of infigratinib and packaging on a regular basis, at the end of 
the study, or at the time of study drug discontinuation.  Drug accountability will be assessed by 
the investigator and/or study personnel, and captured in a subject drug accountability log.  This 
information must be captured in the source document at each subject visit.  
At study close-out, infigratinib can be destroyed at the site if permitted by local regulations.  
Alternatively, the study drug can be destroyed at a third-party depot.  
6. 
DOSE MODIFICATIONS  
Individually, each subject will be allowed up to dose-reduce to 75 mg infigratinib, as follows (see 
also Table 5).  
 
If a subject’s infigratinib dose is 125 mg, 2 dose reductions of infigratinib are permitted.  
 
If a subject’s infigratinib dose is 100 mg, 1 dose reduction of infigratinib is permitted.  
 
If a subject’s infigratinib dose is 75 mg, no dose reduction of infigratinib is permitted, with 
infigratinib treatment discontinuation the only option.  
Subjects should discontinue infigratinib if toxicities persist following dose reductions to the 
lowest level allowed, unless it has been discussed and approved by the QED Therapeutics’ 
Medical Monitor.  
Following resolution of toxicity to baseline or ≤ Grade 1, or ≤ Grade 2 for hematologic toxicities, 
treatment is resumed at either the same or lower dose of study drug as per the criteria in 
Table 6.  Adverse event lab abnormalities outlined in Table 6 should be followed at least weekly 
until the specified resolution.  If treatment is resumed at the same dose of study drug, and the 
same toxicity recurs with the same or worse severity regardless of duration, dose must be 
reduced to the next lower dose level.  If treatment is resumed at the lower dose of study drug, 
and the same toxicity recurs with the same or worse severity, the subject should have a second 
dose reduction.  
Subjects who are withdrawn from the study for a study related AE or an abnormal laboratory 
value must be followed as described in Section 7.3. 
Table 5.  Dose Modification Scheme for Infigratinib 
Dose Reduction  
Dose level 3 
(Starting) Dose level 2 
Dose level 1 
Infigratinib 
125 mg 
100 mg 
75 mg 


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In exceptional situations, study drug may continue even if the subject experienced one of the 
treatment stopping rules.  The decision to allow for continuation of treatment will be made on a 
case-by-case basis following discussion between QED Therapeutics and the investigator. 
Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
CARDIAC DISORDERS 
Cardiac - Prolonged QTcF Interval 
Grade 1 and 2:  QTcF ≥ 481msec 
and  ≤ 500 msec (asymptomatic) 
Maintain dose level of infigratinib.  
Two additional ECGs separated by at least 5 minutes should be 
performed to confirm the finding.  If the finding is confirmed, single 
ECG assessments should be performed every 2 weeks for 
2 additional cycles, or as clinically indicated.  If abnormality is 
detected, 2 additional ECGs separated by at least 5 minutes should 
be performed to confirm the finding.  
 If ECG assessments show no QTcF ≥ 481 msec, for subsequent 
cycles ECG monitoring will be performed at each subsequent visit, 
per visit schedule.  
 If ECG assessments are still abnormal (QTcF ≥ 481 msec and 
≤ 500 msec), then ECG monitoring must continue every 2 weeks 
for all subsequent cycles. 
Grade 3:  QTcF > 500msec or 
> 60 ms change from baseline as 
identified on the ECG by the 
investigator 
Hold infigratinib.  Two additional ECGs separated by at least 5 
minutes should be performed to confirm the finding.  If the finding is 
confirmed, the subject should be admitted to the hospital for at least 
24 hours of continuous telemetry; once confirmed no further 
prolongation of QTc and no arrhythmias over 24 hour period, subject 
can be discharged.  After discharge, subject should return to clinic 
weekly for ECG until normalization.  
 Exclude other causes of QTcF prolongation such as hypokalemia, 
hypomagnesaemia, and decreased blood oxygenation.  
 Subjects should receive appropriate electrolyte replacement and 
should not receive further infigratinib until electrolytes are 
documented to be within normal limits.  
Once the QTcF prolongation has resolved, subjects may be re-treated 
at one lower dose level at the investigator’s discretion. 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
Grade 3:  QTcF > 500msec or 
> 60 ms change from baseline as 
identified on the ECG by the 
investigator (continued) 
Single ECG assessments should be performed for 2 additional cycles 
every 2 weeks or as clinically indicated.  If abnormality is detected, 2 
additional ECGs separated by at least 5 minutes should be performed 
to confirm the finding.  
 If ECG assessments show no QTcF ≥ 481 msec, ECG monitoring 
will be performed at each subsequent visit, per visit schedule for 
subsequent cycles.  
 If ECG assessments are still abnormal (QTcF ≥ 481 msec and 
≤ 500 msec), then ECG monitoring must continue every 2 weeks or 
as clinically indicated, for all subsequent cycles.  
 Subjects who experience recurrent QTcF ≥ 500msec after one 
dose reduction will be withdrawn from study.  
If QTcF > 500 msec or > 60 msec change from the baseline is 
observed, a plasma sample for determination of infigratinib 
concentration should be obtained with the time of sample collection 
noted. 
Grade 4:  Torsade de pointes or 
polymorphic ventricular 
tachycardia or signs/symptoms of 
serious arrhythmia 
Discontinue infigratinib.  
A plasma sample for determination of infigratinib concentration should 
be obtained with the time of sample collection noted. 
Cardiac Disorders – Others 
Grade ≥ 3 OR Congestive heart 
failure Grade ≥ 2 
Discontinue infigratinib. 
INVESTIGATIONS-HEMATOLOGY * 
ANC Decreased (Neutropenia)* 
Grade 3 (ANC 
< 1.0 to 0.5 × 109/L) 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 2 or 
baseline, then  
 If resolved within ≤ 7 days, maintain dose level of infigratinib  
 If resolved between > 7 days and 14 days, decrease by 
1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Grade 4 (ANC < 0.5 × 109/L) 
Hold dose of infigratinib until resolved to CTCAE ≤ Grade 2, decrease 
by 1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
Febrile Neutropenia * 
General Comment:  Consider administering G-CSF per NCCN guidelines (Version 2.2019) “Management 
of Neutropenia”:  that is, if any of the following risk factors for an infection-associated complication are 
present – sepsis syndrome, age > 65 years, ANC < 100/mcL, clinically documented infection, invasive 
fungal infection, hospitalization at the time of fever, or prior episode of febrile neutropenia. 
Grade 3 (ANC < 1.0 × 109/L, 
single temperature of > 38.3°C or 
a sustained temperature 
of ≥ 38.0°C) 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 2, then  
 If resolved within ≤ 7 days, decrease by 1 dose level of infigratinib.  
 If not resolved within 7 days, discontinue subject from study drug 
Grade 4 
Discontinue infigratinib. 
Anemia *  
General Comment:  Consider packed RBC transfusion for hemoglobin < 7 g/dL, or < 8 g/dL for subjects 
with preexisting cardiovascular disease, per AABB guidelines, or if the investigator suspects the subject is 
symptomatic from anemia.   
Grade 3 (hemoglobin < 8.0 g/dL) 
Hold dose of infigratinib until resolved or corrected to CTCAE 
Grade ≤ 2 or baseline, then maintain dose level 
Grade 4 
Hold dose of infigratinib until resolved or corrected to CTCAE 
Grade ≤ 2 or baseline, then decrease by 1 dose level 
Platelet Count Decreased (Thrombocytopenia) * 
Grade 3 (platelet 
< 50 to 25 × 109/L) without 
≥ Grade 2 bleeding 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 2 or 
baseline  
 If resolved within ≤ 7 days, maintain dose level of infigratinib  
 If resolved between > 7 days and 14 days, decrease by 
1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Grade 3 (platelet 
< 50 to 25 × 109/L) with bleeding 
or Grade 4 (platelet < 25 × 109/L) 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 2 or 
baseline, then decrease by 1 dose level  
 If not resolved within ≤ 14 days, discontinue infigratinib 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
INVESTIGATIONS – RENAL 
Serum Creatinine 
Grade ≥ 2 
If serum creatinine CTCAE Grade ≥ 2 has been demonstrated in 
conjunction with hyperphosphatemia, serum creatinine levels must be 
repeated at least weekly until resolution.  24-hour urine collection 
should be obtained as clinically indicated for total phosphate, calcium, 
protein, and creatinine clearance.  Ultrasound examination of the 
kidneys should be performed as indicated to evaluate de-novo 
calcifications until resolution or stabilization of creatinine. 
Grade 2 (≥ 2.00 to 3.0 × ULN or 
2.0 to 3.0 × baseline) 
Hold dose of infigratinib until resolved to Grade ≤ 1 or baseline  
 If resolved within ≤ 7 days, maintain dose level of infigratinib  
 If resolved between > 7 days and 14 days, decrease by 
1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Grade ≥ 3 (> 3.0 × ULN or 
> 3 × baseline) 
Discontinue infigratinib 
INVESTIGATIONS – HEPATIC 
AST or ALT 
 
Grade 3 (> 5.0 to 20.0 × ULN) 
without bilirubin elevation 
> 2.0 × ULN 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 1 or 
baseline  
 If resolved within ≤ 7 days, decrease by 1 dose level of infigratinib  
 If not resolved within ≤ 7 days, discontinue infigratinib 
Grade 4 (> 20.0 × ULN) without 
bilirubin elevation > 2.0 × ULN 
Discontinue infigratinib 
AST or ALT and Bilirubin 
AST or ALT > 3.0 to 5.0 × ULN 
and total bilirubin > 2.0 × ULN 
without liver metastasis or 
evidence of disease progression 
in the liver 
Hold dose of infigratinib until both transaminases and bilirubin 
resolved to CTCAE Grade ≤ 1 or baseline.  
 If resolved within ≤ 7 days, decrease by 1 dose level of infigratinib.  
 If not resolved within ≤ 7 days, discontinue infigratinib 
AST or ALT > 5.0 × ULN and total 
bilirubin > 2.0 × ULN 
Discontinue infigratinib 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
LABORATORY / METABOLIC DISORDERS 
Asymptomatic Amylase and/or Lipase Elevation 
General Comment: Assess for symptoms of acute pancreatitis (abdominal pain or tenderness), and, if 
present, consider a CT scan or other imaging study to assess the pancreas, liver, and gallbladder to 
confirm the diagnosis of acute pancreatitis and assess for complications. 
Grade 3 (> 2.0 to 5.0 × ULN) 
 Hold dose of infigratinib until resolved to CTCAE Grade ≤ 2  
 decrease by 1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
For recurrent Grade 3 asymptomatic lipase or amylase elevation 
despite dose reduction, infigratinib should be held and continuation of 
therapy should be discussed with the medical monitor following 
resolution to ≤ Grade 2. 
Grade 4 (> 5.0 × ULN) 
For any Grade 4 asymptomatic lipase or amylase elevation, 
infigratinib should be held and continuation of therapy should be 
discussed with the medical monitor following resolution to ≤ Grade 2. 
Hyperphosphatemia 
Serum phosphorus 
> 5.5 to 7.0 mg/dL 
Maintain dose level of infigratinib and optimize phosphate lowering 
therapy (see “Management of Hyperphosphatemia” in Section 4.2). 
Serum phosphorus > 7.0 mg/dL 
If serum phosphorus is > 7.0 mg/dL, serum phosphorus should be 
monitored every 2 to 3 days until ≤ 7.0 mg/dL.  
For serum phosphorus that is > 7.0 mg/dL for more than 7 days, or for 
a single serum phosphorus > 9.0 mg/dL:  
 Hold infigratinib dose until resolved to serum 
phosphorus ≤ 5.5 mg/dL.  
For serum phosphorus that is > 7.0 mg/dL for more than 7 days:  
 Restart infigratinib at the same dose level with increased 
phosphate binder dosing if the subject did not receive maximal 
phosphate binder dosing (sevelamer 1600 mg 3 times daily).  
 Reduce one dose level of infigratinib if the subject had received 
maximal phosphate lowering therapy (sevelamer 1600 mg 
three times daily).  Continue maximal phosphate binder dosing.  
For serum phosphorus that is > 9.0 mg/dL:  
 Reduce one dose level of infigratinib.  Restart infigratinib with 
maximal phosphate binder dosing.  
It is recommended that phosphate binder dosing continues during 
infigratinib dose interruptions for hyperphosphatemia. 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
Hypercalcemia 
Serum calcium Grade 2 
Hold infigratinib dose until resolved to Grade 1 or baseline:  
 If resolved within ≤ 7 days after suspending infigratinib, maintain 
dose level  
 If resolved between > 7 days and 14 days after suspending 
infigratinib, decrease by 1 dose level  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Serum calcium ≥ Grade 3 
Discontinue subject from study drug 
NERVOUS SYSTEM DISORDERS 
Any Grade 2 neurotoxicity 
Omit dose of infigratinib until resolved to CTCAE Grade ≤ 1, then 
decrease by 1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Any Grade ≥ 3 neurotoxicity 
Discontinue infigratinib 
GASTROINTESTINAL SYSTEM DISORDERS 
Pancreatitis 
Grade ≥ 2 
Discontinue infigratinib 
Diarrhea 
General Comment:   
Antidiarrheal medication is recommended at the first sign of 
abdominal cramping, loose stools or overt diarrhea 
Grade 1 
Maintain dose level of infigratinib, initiate anti-diarrheal treatment  
Grade 2 
 Hold dose of infigratinib until resolved to CTCAE Grade ≤ 1  
 Optimize anti-diarrheal treatment  
 For reoccurrence of diarrhea CTCAE Grade 2, hold dose of 
infigratinib until resolved to CTCAE Grade ≤ 1, decrease infigratinib 
by 1 dose level 
Grade 3 
 Hold dose of infigratinib until resolved to CTCAE Grade ≤ 1  
 Optimize anti-diarrheal treatment  
 Decrease infigratinib by 1 dose level  
 For reoccurrence of diarrhea CTCAE Grade 3, despite optimal 
antidiarrheal treatment, discontinue infigratinib 
Grade 4 
Discontinue infigratinib 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
Vomiting 
 
Grade 2 not controlled by optimal 
anti-emetic therapy 
Hold infigratinib doses until ≤ Grade 1, decrease by 1 dose level  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Grade 3 not controlled by optimal 
anti-emetic therapy, or Grade 4 
Discontinue infigratinib 
EYE DISORDERS (CONFIRMED BY OPHTHALMOLOGIC EXAMINATION) 
Retinal Disorders 
Grade 2 central serous 
retinopathy and central serous 
retinopathy -like events 
Hold infigratinib until resolved to ≤ Grade 1 and continue 
ophthalmologic evaluation  
 If resolved within ≤ 14 days, decrease infigratinib by 1 dose level  
 If resolved after > 14 days, discontinue infigratinib 
Grade ≥ 1 retinal vein occlusion, 
Grade 3 or 4 central serous 
retinopathy and central serous 
retinopathy-like events, and 
Grade 3 or 4 other eye disorders 
Discontinue infigratinib 
Other Ocular/Visual Toxicity 
Grade ≥ 3 
Discontinue infigratinib 
  
SKIN DISORDERS 
Palmar-plantar erythrodysesthesia syndrome 
Grade 3 
Hold dose of infigratinib until resolved to Grade ≤ 1, and then resume 
infigratinib at decrease by 1 dose level 
Paronychia 
Grade 3 
Hold dose of infigratinib until resolved to Grade ≤ 1, and then resume 
infigratinib at decrease by 1 dose level. 
Stomatitis 
Grade 3 
Hold dose of infigratinib until resolved to Grade ≤ 1, and then resume 
infigratinib at decrease by 1 dose level. 
Grade 4 
Discontinue infigratinib 


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Table 6.  Criteria for Interruption and Re-initiation of Infigratinib for AEs Considered to be 
Possibly Related to Infigratinib 
Worst Toxicity CTCAE (v5.0) 
Grade (Unless Otherwise 
Specified) 
Recommended Dose Modifications any Time During a Cycle of 
Therapy 
GENERAL DISORDERS 
Fatigue 
Grade ≥ 3 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 1  
 If resolved within ≤ 7 days, maintain dose level of infigratinib.  
 If resolved after > 7 days, discontinue infigratinib 
OTHER CLINICALLY SIGNIFICANT AEs 
Grade 3 
Hold dose of infigratinib until resolved to CTCAE Grade ≤ 1, then 
decrease by 1 dose level of infigratinib  
 If not resolved within ≤ 14 days, discontinue infigratinib 
Grade 4 
Discontinue infigratinib 
Abbreviations:  AE, adverse event; ALT, alanine aminotransferase; ANC, absolute neutrophil count; AST, 
aspartate aminotransferase; CT, computed tomography; CTCAE, Common Terminology Criteria for 
Adverse Events; ECG, electrocardiogram; QTcF, QTc corrected by Fridericia's formula; ULN, upper limit of 
normal.  
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES  
7.1 
Potential Adverse Events  
7.1.1 Related to Study Drug (Infigratinib)  
 
Adverse events related to calcium/phosphorous homeostasis are expected and 
on-target effects of infigratinib.  Hyperphosphatemia in particular is a reliable 
biomarker of pathway inhibition and rapidly normalizes upon drug discontinuation 
without sequelae.  Among 433 subjects treated with infigratinib monotherapy, 
hyperphosphatemia was seen in 62% and in 7% it was Grade 3 or 4.  Adverse 
events associated with calcium/phosphate imbalance (including soft tissue 
mineralization or ectopic calcifications) have been rare.  There have been 
3 suspected unexpected SAEs reported related to calcium/phosphorus homeostasis:  
(1) hepatic failure due to lesion calcification occurring over 6 months after study drug 
discontinuation, (2) one episode of hypercalcemia, and (3) one episode of 
hypophosphatemia/hypocalcemia.  
 
Ophthalmologic adverse events may occur with infigratinib, and mandated 
ophthalmologic examinations have been performed routinely and frequently.  Most of 
these events are Grade 1 or 2: for example, dry eye in 22% and blurry vision in 10%.  
Grade 3 ocular events have occurred in 3%, and no Grade 4 ocular events have 
occurred.  Grade 3 ocular events included cataract (0.7%), visual impairment (0.5%), 
and keratitis (0.5%).   
 
Gastrointestinal adverse events are frequently reported.  For subjects treated with 
monotherapy, the most frequent GI AEs (regardless of relationship to study drug) 
were constipation (37%), decreased appetite (30%), nausea (29%), diarrhea (27%), 
vomiting (20%), and dyspepsia (15%).  Stomatitis was reported in 35%, and in 5% 
was Grade 3 or 4.  


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 
Skin, hair, and nail changes are frequently reported.  For subjects treated with 
monotherapy, 27% experienced alopecia, 13% experienced dry skin, and 12% 
experienced palmar-plantar erythrodysaesthesia syndrome. 
 
For others, please see Section 2.2 (especially Tables 2 to 4) and the 
Investigator’s Brochure.  
7.1.2 Related to Tamoxifen (Cohort 1) (reported percentages are from N = 3,094 subjects in 
the ATAC trial)  
 
Hot flashes (64%) (placebo 48%)  
 
Vaginal discharge (30%) (placebo 15%)  
 
Nausea (26%) (placebo 24%)  
 
Fluid retention (32%) (placebo 30%)  
 
Mood disturbances  
 
Thrombotic events (0.8% deep vein thrombosis, 0.5% pulmonary embolism, 0.4% 
superficial phlebitis)  
 
For others, please see tamoxifen package insert from the FDA.  
7.2 Adverse Event Definitions  
An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), 
symptom(s), or medical condition(s).  
An SAE is defined as one of the following:  
 
Is fatal or life-threatening  
 
Results in persistent or significant disability/incapacity  
 
Constitutes a congenital anomaly/birth defect  
 
Is medically significant, ie, defined as an event that jeopardizes the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed above  
 
Requires in-patient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition  
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent  
o Treatment on an emergency out-patient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission  
o Social reasons and respite care in the absence of any deterioration in the subject’s 
general condition  
Abnormal laboratory values or test results constitute AEs only if they induce clinical signs or 
symptoms, are considered clinically significant, require therapy (eg, hematologic abnormality 
that requires transfusion or hematological stem cell support), or require changes in study 
drug(s).  
Progression of underlying malignancy is not considered as an AE if it is clearly consistent with 
the suspected progression of the underlying cancer as defined by RECIST criteria v1.1, or other 


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criteria as determined by protocol.  Hospitalization due solely to the progression of underlying 
malignancy should NOT be reported as an SAE.  
Clinical symptoms of progression may be reported as AEs if the symptom cannot be determined 
as exclusively due to the progression of the underlying malignancy, or does not fit the expected 
pattern of progression for the disease under study.  
Symptomatic deterioration may occur in some subjects.  In this situation, progression is evident 
in the subject’s clinical symptoms, but is not supported by the tumor measurements.  Or, the 
disease progression is so evident that the investigator may elect not to perform further disease 
assessments.  In such cases, the determination of clinical progression is based on symptomatic 
deterioration.  These determinations should be a rare exception as every effort should be made 
to document the objective progression of underlying malignancy.  
If there is any uncertainty about an AE being due to progression of the disease under study, it 
should be reported as an AE or SAE.  
7.3 
Adverse Events Reporting 
Adverse events (AEs) will be documented and recorded at each scheduled or unscheduled visit, 
including end-of-treatment and during follow-up, using NCI CTCAE v5.0.  Subjects will be 
followed for AEs for 30 days after the last treatment administration or until all drug-related 
toxicities have resolved (or the Investigator determines in his/her clinical judgment that no 
further improvement is expected), whichever is later.  For serious adverse events (SAEs), the 
active reporting period will be from the time that the subject provides informed consent, which is 
obtained prior to the subject’s participation in the study, ie, prior to undergoing any study-related 
procedure and/or receiving investigational product, through and including 30 calendar days after 
the last administration of the investigational product.  SAEs experienced by a subject after the 
active reporting period has ended should be reported if the Investigator becomes aware of 
them.  
Conditions already present at the time of informed consent should be recorded in the Medical 
History CRF.  
AEs (including lab abnormalities that constitute AEs) should be described using a diagnosis 
whenever possible, rather than individual underlying signs and symptoms.  When a clear 
diagnosis cannot be identified, each sign or symptom should be reported as a separate AE.  
The following information is to be captured in the CRF for each AE:  severity grade 
(CTCAE v5.0, Grade 1 to 5); duration (start and end dates); relationship to study drug 
(infigratinib or tamoxifen) (reasonable possibility that AE is related:  No, Yes); action taken with 
respect to study drug (none, dose reduction, temporarily interrupted, permanently discontinued, 
unknown, not applicable); whether medication or therapy was given (no concomitant 
medication/non-drug therapy given, concomitant medication/non-drug therapy given); outcome 
(not recovered/not resolved, recovered/resolved, recovering/resolving, recovered/resolved with 
sequelae, fatal, unknown); and whether the event is serious and seriousness criteria.  
7.4 
Reporting Serious Adverse Events  
Every SAE, regardless of suspected causality, occurring after the subject has signed informed 
consent through 30 days after the subject has taken his/her last dose of study drug, will be 


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reported to the Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) using 
the study-specific CRF, and to Helsinn Healthcare SA by email (drug-safety@helsinn.com) 
using their provided CRFs, within 24 hours of learning of its occurrence.  Following review by 
the Stanford DSMC, events meeting the IRB definition of ‘Unanticipated Problem’ will be 
reported to the IRB using eProtocol within 10 working days of DSMC review, or within 
5 working days for deaths or life-threatening experiences.  Any SAEs experienced after this 
30-day period should only be reported to the DSMC if the investigator suspects a causal 
relationship to the study drug.  
Any additional information for the SAE including recurrent episodes, complications, or 
progression of the initial SAE must be reported as follow-up to the original episode within 
24 hours of the investigator receiving the follow-up information.  An SAE occurring at a different 
time interval or otherwise considered completely unrelated to a previously reported one should 
be reported separately as a new event.  
Follow-up information is submitted in the same way as the original SAE Report.  Each 
reoccurrence, complication, or progression of the original event should be reported as a 
follow-up to that event regardless of when it occurs.  The follow-up information should describe 
whether the event has resolved or continues, if and how it was treated, and whether the subject 
continued or withdrew from study participation.  
If the SAE is not an expected event as per the current Investigator’s Brochure or Package Insert 
(new occurrence or increased frequency) and is thought to be related to the study drug (a 
Suspected Unexpected Serious Adverse Reaction, “SUSAR”), it must also be reported to 
Helsinn Healthcare SA via email (drug-safety@helsinn.com) using their provided CRFs within 
24 hours of learning of the event and to the FDA via an IND Safety Report within 15 days 
(7 days if life-threatening or death).  QED Therapeutics and partner, the Helsinn Group, will be 
responsible to send investigator notifications to investigators involved with infigratinib studies.  
7.5 
Pregnancy  
Female subjects must be discontinued from study drug in the event of pregnancy.  
To ensure subject safety, each pregnancy of a subject or partner of a male subject occurring 
while the subject is on study drug must be reported to the Stanford DSMC and Helsinn 
Healthcare SA (via email at drug-safety@helsinn.com) using their provided CRFs within 
24 hours of learning of its occurrence.   
For Stanford DSMC reporting, the pregnancy should be followed up to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications.  Consent to report information regarding pregnancy and pregnancy outcomes 
should be obtained from the partner of the male subject.  Pregnancy of a subject or partner of a 
male subject should be recorded on a Pregnancy Notification Form and entered on the 
Pregnancy eCRF.  Pregnancy follow-up should be recorded and include an assessment of the 
possible relationship to the study drug of any pregnancy outcome.  Pregnancy and pregnancy 
follow-up should be reported to the Stanford DSMC and Helsinn Healthcare SA (via email at 
drug-safety@helsinn.com) using their provided CRFs.  


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8. 
CORRELATIVE/SPECIAL STUDIES  
Two types of specimens, tumor tissues and plasma, will be collected for correlative studies. 
8.1 
Laboratory Correlative Studies 
8.1.1 Tumor Tissue Collection and Processing 
8.1.1.1 Collection of Specimen(s) 
Fresh tumor tissue will be collected on subjects participating in the study during the 
pre-treatment and on-treatment research biopsies, which are mandatory if deemed safe 
and feasible by the investigator.  Procedures will be done according to best clinical 
practice guidelines as are all procedures at Stanford Hospital.  Four to eight 
research-specific core biopsies will be taken, depending on the biopsy site and 
investigator assessment of safety and feasibility.  Research biopsies will not be taken if 
there is felt to be more than minimal additional risk.   Details on processing of specimens 
are provided in the lab manual. 
8.1.1.2 Coding of specimens for privacy protection 
Study staff (eg, the protocol director or clinical research coordinator) will create a 
unique anonymous identifier for each specimen at time of subject data collection and 
entry into the secure REDCap database.  The unique anonymized identifier will be 
assigned sequentially within each cohort (eg, INF1001, INF1002, etc; INF2001, 
INF2002, etc).  All tissue specimens will be labeled with this anonymous identifier and 
no subject-identifiable information.  The link between anonymous identifier and subject 
information will be stored in the secure REDCap database. 
8.1.2 Plasma Collection and Processing  
8.1.2.1 Collection of Plasma Specimen(s)  
20 cc of blood will be collected in black and tan top Streck Cell-Free DNA BCT tubes at 
screening or on Cycle 1 Day 1, on Cycle 1 Day 15 (± 3 days), and then again at End of 
Treatment.  Details on processing of specimens are provided in the lab manual. 
8.1.2.2 Coding of specimens for privacy protection 
As with the tissue specimens (Section 8.1.1), plasma specimens will be labeled with the 
same anonymous identifier and no subject-identifiable information.  The link between 
anonymous identifier and subject information will be stored in the secure REDCap 
database. 


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9.  STUDY CALENDAR 
Protocol Activity 
Screening 
On Treatment (1 Cycle = 28 days) 
Post-Treatment 
(Within  
21 days of 
Cycle 1, 
Day 0) 
Cycle 1 
Cycle 2 
Cycles  3 
End of Treatment / 
withdrawal (0 to 14 days 
from decision to 
discontinue) 23 
30-day 
Follow-up 
Safety Visit 
(+ 7 days) 24 
Other 
Follow-up25 
Day 1 
(± 3 days) 
Day 4 
(± 1 day) 
Day 15 
(± 3 days) 
Day 1 
(± 3 days) 
Day 15 
(± 3 days) 
Day 1 (± 3 days) 
Informed Consent 1 
X 
 
 
 
 
 
 
 
 
 
Medical/Tumor History 2 
X 
 
 
 
 
 
 
 
 
 
Physical Examination (within 
24 hours prior to start of each 
cycle)3 
X 
X 
 
X 
X 
 
X 
X 
X 
(X) 
ECOG Performance Status 4 
X 
X 
 
X 
X 
 
X 
X 
X 
(X) 
Safety Labs/Measurements 
Vital Signs (within 24 hours 
prior to start of each cycle) 5 
X 
X 
 
X 
X 
 
X 
X 
X 
(X) 
Hematology (CBC, differential, 
platelets) 6 
X 
X 
 
X 
X 
X 
X 
X 
 
(X) 
Complete metabolic panel 7 
X 
X 
X 
X 
X 
X 
X 
X 
 
(X) 
Amylase, lipase 8 
X 
X 
 
X 
X 
X 
X 
X 
 
(X) 
Calcium, magnesium, 
phosphorus 9 
X 
X 
X 
X 
X 
X 
X 
X 
 
(X) 
Urinalysis 10 
X 
 
 
 
 
 
 
 
 
 
Pregnancy Test 11 
X 
X 
 
 
 
 
 
X 
 
 
Electrocardiogram 12 
X 
 
 
 
X 
 
C4D1, C6D1 (± 7 days) then 
every 6 cycles (all ± 14 days) 
X 
 
 
Transthoracic echocardiogram 
13 
X 
 
 
 
X 
 
 
X 
 
 
Ophthalmology evaluation 14 
X 
 
 
 
X ± 7 da
ys 
 
C3D1, C4D1, C6D1 (± 7 days), 
then every 3 cycles (± 14 days) 
X 
 
 


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Protocol Activity 
Screening 
On Treatment (1 Cycle = 28 days) 
Post-Treatment 
(Within  
21 days of 
Cycle 1, 
Day 0) 
Cycle 1 
Cycle 2 
Cycles  3 
End of Treatment / 
withdrawal (0 to 14 days 
from decision to 
discontinue) 23 
30-day 
Follow-up 
Safety Visit 
(+ 7 days) 24 
Other 
Follow-up25 
Day 1 
(± 3 days) 
Day 4 
(± 1 day) 
Day 15 
(± 3 days) 
Day 1 
(± 3 days) 
Day 15 
(± 3 days) 
Day 1 (± 3 days) 
Registration 1 
 7 days bef 
Cycle 1, 
Day 1 
 
 
 
 
 
 
 
 
 
Treatment 
Infigratinib administration 15 
 
Daily as 3 weeks on / 
1 week off 
 for entire cycle 
3 weeks on / 
1 week off 
3 weeks on / 
1 week off 
 
 
 
Cohort 1:  Tamoxifen 
administration 16 
 
 
Continuous 
Continuous 
Continuous 
 
 
 
Tumor Assessment 
CT (chest, abdomen, pelvis) 17 
X 
 
 
 
 
 
C3D1 (+7 days), then every 
2 cycle (± 7 days) 
(X) 
 
 
Plasma collection 18 
 
X 
 
X 
 
 
 
X 
 
 
Research tumor biopsy 19 
X 
 
 
X 
 
 
 
 
 
 
Tumor sequencing 20 
X 
 
 
 
 
 
 
 
 
 
Other Clinical Assessment 
Adverse event assessment 21 
X 
Monitor and record at every study visit 
X 
X 
X 
Concomitant medications 22 
X 
Monitor and record at every study visit 
X 
X 
 
1.  Informed Consent:  Must be obtained prior to undergoing any study specific procedure and may occur prior to the 21-day screening period.  Registration will considered to be 
signed informed consent with triple-signed eligibility checklist, with the final signature being the Stanford Principal Investigator or his/her designee.  
2.  Medical History / Tumor History:  To be collected within 21 days prior to C1D1.  Includes history of other diseases (active or resolved) and concomitant illnesses.  Oncology 
history includes information on prior regimens (including dosing and duration of administration, description of best response observed, recurrence date), surgery and radiation 
therapy.  It also includes review of the predicted integrative subtype from FoundationOne.  These assays may also be done during screening, as indicated (see footnote 22, “Tumor 
sequencing”).  
3.  Physical Examination:  Includes an examination of major body systems.  Weight for the purposes of dose calculation will be recorded at screening and within 7 days pre-dose 
Day 1 of each cycle.  Weight will also be collected at End of Treatment.  Height will be measured at baseline.  


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4.  ECOG Performance Status:  
Score 
Definition  
0 
Fully active, able to carry on all pre-disease activities without restriction  
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work or office work  
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities.  Up and about more than 50% of waking hours  
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours  
4 
Completely disabled.  Cannot carry on any selfcare.  Totally confined to bed or chair  
5 
Dead  
5.  Vital signs:  Blood pressure, pulse rate, and body temperature to be recorded in the same position, either supine or sitting.  
6.  Hematology:  No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  On treatment, to be performed prior to dosing with study 
medications unless otherwise indicated.  Lab abnormalities that are adverse events specified in Table 6 must be followed at least weekly until resolution to the grade specified in 
Table 6.  
7.  Complete metabolic panel:  No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  Lab abnormalities that are adverse events 
specified in Table 6 must be followed at least weekly until resolution to the grade specified in Table 6.  
8.  Amylase, lipase:  No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  Lab abnormalities that are adverse events specified in 
Table 6 must be followed at least weekly until resolution to the grade specified in Table 6.  
9.  Calcium, magnesium, phosphorus (serum):  No need to repeat on C1D1 if baseline assessment performed within 72 hours prior to that date.  Lab abnormalities that are 
adverse events specified in Table 6 must be followed at least weekly until resolution to the grade specified in Table 6.  
10.  Urinalysis:  Macroscopic or microscopic.  
11.  Pregnancy Test:  For female subjects of childbearing potential, a serum or urine pregnancy test must be performed within 7 days of first day of study drug and at 
end-of-treatment.  Additional pregnancy test to be repeated when potential pregnancy is suspected.  
12.  Electrocardiogram:  12-lead ECG to be performed during Screening, at Cycle 2 Day 1 (± 3 days), Cycle 4 Day 1 (± 7 days), Cycle 6 Day 1 (± 7 days), and then every 6 cycles 
(± 14 days), and at End-of-Treatment.  Additional assessments should be conducted as clinically indicated. 
13.  Echocardiogram:  Transthoracic echocardiogram to be performed during Screening, at Cycle 2 Day 1 (± 3 days), and at End-of-Treatment.  Additional assessments should be 
conducted as clinically indicated.  
14.  Ophthalmology evaluation:  Ophthalmologic examination will be performed by an ophthalmologist during Screening, on Day 1 (± 7 days) of Cycles 2, 3, 4 and 6;  then every 
3 cycles (± 14 days);  and at End-of-Treatment, as well as urgently with any new onset of visual symptoms.  These assessments will include visual acuity testing, slit lamp 
examination of the anterior eye segment, intraocular pressure, dilated fundoscopy, and retinal optical coherence tomography (OCT).  Additional examinations such as specular 
microscopy (that enables a magnified, direct view of the corneal epithelium) and corneal pachymetry will be performed as clinically indicated.  
15.  Infigratinib Administration:  One cycle of infigratinib will be provided to subjects at the beginning of each cycle.  Starting dose level of infigratinib for individual subjects will be 
as defined by study protocol, and may be either 125 mg;  100 mg;  or 75 mg infigratinib, each dose level administered as 3 weeks on, 1 week off for every 28-day cycle.   
16.  Tamoxifen Administration:  In Cohort 1, tamoxifen will be prescribed to subjects and will be started at 4 to 8 hours after the administration of infigratinib, starting on Cycle 1 
Day 1.  Dose is tamoxifen 20 mg/day by mouth continuously.  
17.  Tumor assessment by imaging:  Baseline CT imaging can be done within 28 days prior to C1D1 (versus 21 days for all other baseline/screening assessments).  Assessment 
of response will be made using RECIST v1.1.  Antitumor activity will be assessed through radiological tumor assessments conducted at baseline, on treatment every 8 weeks and 
whenever disease progression is suspected (eg, symptomatic deterioration).  After 12 months of therapy, imaging can be spaced out to every 12 weeks at the Investigator’s 
discretion.  To be repeated at End of Treatment/Withdrawal only if not done in the previous 4 weeks.  Confirmation of response (CR/PR) should be done at least 4 weeks after the 
initial response.  The allowable time window for disease assessments is ± 7 days, on treatment, starting from C1D1, except for the first post baseline assessment (+ 7-day window 
allowed).  Timing should follow calendar days and should not be adjusted for delays in cycle starts.  


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18.  Plasma collection:  Two Streck tubes will be collected on Cycle 1 Day 1 prior to study drug initiation, on Cycle 1 Day 15 (± 3 days), and at End of Treatment.  Buffy coat 
separated from the same blood collection will be used for tumor-normal sequencing. 
19.  Tumor biopsy:  A pre-treatment and on-treatment tumor biopsy is mandatory if deemed safe (not posing more than minimal additional risk) and feasible by the investigator.  
The on-treatment tumor biopsy is recommended to be performed on or around Day 15 of therapy, but can be performed at any time on therapy per protocol.  
20.  Tumor sequencing:  If a potential subject has not had FoundationOne tumor sequencing performed, allowing assessment of predicted integrative subtype, this assay may be 
sent to determine eligibility.  
21.  Adverse event assessments:  Adverse events (AEs) will be documented and recorded at each scheduled or unscheduled visit, including end-of-treatment and during 
follow-up, using NCI CTCAE v5.0.  Subjects will be followed for AEs for 30 days after the last treatment administration or until all drug-related toxicities have resolved (or the 
Investigator determines in his/her clinical judgment that no further improvement is expected), whichever is later.  For serious adverse events (SAEs), the active reporting period will 
be from the time that the subject provides informed consent, which is obtained prior to the subject’s participation in the study, ie, prior to undergoing any study-related procedure 
and/or receiving investigational product, through and including 30 calendar days after the last administration of the investigational product.  SAEs experienced by a subject after the 
active reporting period has ended should be reported if the Investigator becomes aware of them.  The reporting period for non-serious AEs will be from the time the subject has 
taken at least one dose of study treatment through Day 30 after last dose.  If a subject begins a new anticancer therapy, the AE reporting period for non-serious AEs will end at the 
time the new treatment is started.  
22.  Concomitant medications:  Concomitant medications will be recorded from 30 days prior to the start of study treatment through 30 days after the last dose of study treatment.  
Concomitant medications will be collected at each scheduled or unscheduled visit, including at end-of-treatment.  All concomitant medications should be recorded in the CRF 
including supportive care drugs (eg, anti-emetic treatment and prophylaxis), herbal supplements or vitamins, the drugs used to treat adverse events or chronic diseases, and 
non-drug supportive interventions (eg, transfusions).  
23.  End of Treatment:  To be performed 0 to 14 days after the decision made to discontinue study drug.  Obtain these assessments if not completed during the previous week on 
study.  CT scan should be performed at End of Treatment unless CT scan was performed within the previous 4 weeks.  
24.  30-Day Follow-Up Safety Visit:  Performed 30 to 37 days after last dose of study drug.  Information related to concomitant medications and adverse events will be collected for 
30 days after the last dose of the study drug.  
25.  Follow-Up:  Subjects continuing to experience toxicity following discontinuation of study treatment will continue to be followed including for adverse events, at least every week 
(± 3 days) for 4 weeks, and subsequently every 4 weeks (± 7 days), until resolution or determination, in the clinical judgment of the Investigator, that no further improvement is 
expected.  If a follow-up is required beyond 30 to 37 days after last dose of study drug, not all assessments need to be performed.  Only assessments that are clinically indicated are 
necessary for this timepoint. 


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10. 
MEASUREMENTS  
10.1  Primary endpoint:  
The primary endpoint is the incidence of dose-limiting toxicities (DLTs) in the first 2 cycles of 
therapy at a specific dose.  In Cohort 1, in a subset of subjects who start at infigratinib 100 mg 
and complete 2 cycles with no DLTs and who remain on study for Cycles 3 and 4, the dose of 
infigratinib will be increased to 125 mg starting with Cycle 3 and the number of DLTs in Cycles 3 
and 4 will be counted toward the primary endpoint (for the 125 mg dose), in addition to the 
number of DLTs in Cycles 1 and 2 (for the 100 mg dose).  For all other subjects, the primary 
endpoint will be the number of DLTs in Cycles 1 and 2. 
DLTs will be graded using NCI CTCAE (Common Terminology Criteria for Adverse Events), 
v5.0.  DLTs will be defined as an adverse event (AE) or abnormal laboratory value at least 
possibly related to therapy with infigratinib including those AEs and abnormal laboratory values 
that result in a failure to meet the criteria for re-treatment.  The criteria for defining a DLT, which 
are pre-specified based on the pre-clinical toxicity of infigratinib, are listed in Table 7.  
Individual subjects who had a DLT may be retreated, after recovery, at the next lowest dose 
level.  
Investigators will notify QED Therapeutics within 7 days of any DLTs observed.  
Table 7.  Criteria for defining dose-limiting toxicities 
TOXICITY 
DLT CRITERION 
Skipped/ 
delayed dose 
The inability to administer infigratinib on ≥ 75% of scheduled treatment days 
during cycle 1 at that dose (ie, ≥ 16 days of the 21 days of planned treatment) due 
to unresolved adverse event of any grade and considered at least possibly, 
probably, or definitely related to the study drug.  
Delay in 2nd cycle administration at that dose due to failure of recovery from a 
possibly, probably, or definitely related adverse event to Grade ≤ 1 or baseline by 
Day 43 (Day 28 of Cycle 1 + 15 days), except for alopecia. 
Blood/ bone 
marrow 
Neutropenia  
    • Febrile, CTCAE Grade ≥ 3. 
    • CTCAE Grade ≥ 3 for > 7 consecutive days  
Thrombocytopenia 
    • CTCAE Grade 3 for > 7 consecutive days and/or with signs of  
clinically significant bleeding. 
    • CTCAE Grade 4  
Anemia CTCAE Grade 4 
Renal/ 
genitourinary 
Creatinine: 
    • CTCAE Grade 1 for > 7 consecutive days and serum inorganic phosphorus  
       > 5.5 mg/dL and/or serum total calcium x serum inorganic phosphorus  
       > 55 mg2/dL2 and despite phosphorus lowering therapy for ≥ 14 days  
    • CTCAE Grade 2 for > 7 consecutive days  
    • CTCAE Grade ≥ 3 


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Table 7.  Criteria for defining dose-limiting toxicities 
TOXICITY 
DLT CRITERION 
Hepatic 
Bilirubin: 
    • CTCAE Grade 2 for > 7 consecutive days  
    • CTCAE Grade ≥ 3  
AST or ALT: 
    • Grade 3 for > 7 consecutive days 
    • CTCAE Grade 4 
Hy’s Law 
    • ALT or AST ≥ 3 x upper limit of normal (ULN)  
      AND 
    • Serum total bilirubin > 2 x ULN 
For patients with known hepatic metastases: 
    • AST or ALT > 8 x ULN 
      OR 
    • AST or ALT > 5 x ULN for ≥ 14 days 
Pancreas 
Pancreatitis CTCAE Grade ≥ 2  
Amylase/lipase (serum-high):  CTCAE Grade ≥ 3 asymptomatic amylase and/or  
   asymptomatic lipase not reversible to CTCAE Grade ≤ 2 within 7 days 
Cardiac 
QTcF interval > 500ms  
Other cardiac CTCAE Grade ≥ 3 
Constitutional 
Fatigue CTCAE Grade 3 for > 7 consecutive days  
Fatigue CTCAE Grade 4 
Ocular/visual 
Any ocular/visual toxicity CTCAE Grade ≥ 3. 
Gastrointestinal 
CTCAE Grade 3 or 4 nausea/vomiting and/or diarrhea despite the use anti-emetic 
and anti-diarrhea therapy, respectively 
Metabolic/ 
laboratory 
Hyperphosphatemia (serum-high): 
    • Serum inorganic phosphorus > 7.0 mg/dL for > 7 consecutive days despite  
       phosphorus-lowering therapy for at least 14 days. 
    • Serum inorganic phosphorus > 9.0 mg/dL, despite phosphorus-lowering  
       therapy for at least 14 days. 
    • Serum inorganic phosphorus > 10.0 mg/dL  
Hypercalcemia (serum-high) 
    • Serum calcium CTCAE Grade 2 for > 7 consecutive days. 
    • Serum calcium CTCAE Grade ≥ 3. 
Other 
Any death not clearly due to the underlying disease or known, extraneous causes. 
Clinical evidence for any grade (CTCAE Grade ≥ 1) of ectopic, de-novo- 
calcification within the soft tissue including the peri-articular spaces and vascular 
as well as visceral tissues (eg, kidney, lung, stomach, myocardium, etc.)  
Any other CTCAE Grade 3 or 4 non-hematological toxicity except with following 
exclusions: 
    • Alkaline phosphatase CTCAE Grade ≥ 3. 
    • Lymphocytopenia CTCAE Grade ≥ 3 unless considered clinically significant. 


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10.2 
Secondary endpoints:  
1. Incidence of treatment-emergent adverse events (TEAE).  A TEAE is defined as an 
adverse event with initial onset or increasing in severity after the first dose of study 
treatment until 30 days after last dose of study drug.  TEAEs will be assessed and 
documented at each scheduled or unscheduled visit during the reporting period.  Each 
TEAE will be assessed according to whether it is serious or non-serious, whether it is 
expected or unexpected according to the Investigator’s Brochure, and whether it is 
related or unrelated to the study treatment.  Each TEAE will be assigned a grade 
according to CTCAE v5.0.  A serious adverse event is one that results in death, is 
life-threatening, requires in-patient hospitalization or causes prolongation of existing 
hospitalization, results in persistent or significant disability/incapacity, may have caused 
a congenital anomaly/birth defect, or requires intervention to prevent permanent 
impairment or damage.  Pregnancy during the reporting period will be classified as a 
serious adverse event.  
2. Objective tumor response, per RECIST v1.1 (see Appendix C), in subjects with 
measurable disease.  An objective tumor response can be observed at any time on 
study between 8 weeks after starting therapy (C3D1) through 18 months after starting 
therapy.  
3. Progression-free survival (PFS), defined as the number of days to either progressive 
disease as defined per RECIST v1.1 or death.  
4. Clinical benefit, defined as an objective tumor response or stable disease at 6 months, 
defined per RECIST v1.1 (see Appendix C).  
10.2.1 Measurement Methods  
For those subjects with bone-only disease, RECIST v1.1 criteria will not be used to assess 
response.  Subjects will stop study drug at when disease is deemed by the investigator to have 
progressed.  
10.2.2 Measurement Time Points  
Antitumor activity will be assessed through radiological tumor assessments conducted at 
baseline, on treatment every 8 weeks (± 7 days), and whenever disease progression is 
suspected (eg, symptomatic deterioration).  After 12 months of therapy, imaging can be spaced 
out to every 12 weeks (± 7 days) at the Investigator’s discretion.  Studies will be repeated at 
End of Treatment/Withdrawal only if not done in the previous 4 weeks.  Confirmation of 
response (CR/PR) should be done at least 4 weeks after the initial response.  Timing should 
follow calendar days (starting from C1D1) and should not be adjusted for delays in cycle starts.  
10.3 Outcomes for ClinicalTrials.gov  
The outcomes for ClinicalTrials.gov represent the study objectives.  


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10.3.1 Primary Outcome  
Primary Outcome Title:  Dose-limiting Toxicity (DLT)  
Primary Outcome Measure Description:  The primary outcome for this study is 
dose-limiting toxicities (DLTs) during the first 2 cycles of therapy at a specific dose.  All 
grades per the Common Terminology Criteria for Adverse Events (CTCAE).  DLT is defined 
as a related and clinically-significant adverse event (AE), including missed doses due to a 
related AE.  Due to limited number of characters that can present in this field, it is not 
possible to consistently provide additional details across all sub-elements of this outcome.  
See protocol.  The outcome is expressed as the number of DLT events by the assigned 
infigratinib dose level, a number without dispersion.  
Time Frame:  8 weeks.  
10.3.2 Secondary Outcomes  
1.  Outcome Title:  Treatment-emergent Adverse Events (TEAE)  
Outcome Measure Description:  Treatment-emergent adverse events (TEAEs) are 
defined as adverse events of any grade with initial onset or increasing in severity after 
the first dose of study treatment until 30 days after last dose of study drug.  Pregnancy 
during the reporting period will be classified as a serious adverse event.  The outcome 
will be expressed as the number of events by the infigratinib dose level at the time of the 
event, stratified by relatedness and Common Terminology Criteria for Adverse Events 
(CTCAE) grade.  The result is a number without dispersion.  
Time Frame:  2 years  
2.  Outcome Title:  Objective Tumor Response  
Outcome Measure Description:  Objective tumor response will be assessed as 
achieving a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete 
Response (CR) or a Partial Response (PR).  The outcome will be reported as the 
number of subjects by each participant’s final infigratinib dose level that achieve an 
overall response (OR) to treatment, ie, CR or PR, within 18 months of starting treatment.  
The outcome will be reported as a number without dispersion.  RECIST criteria are:  
• CR = Disappearance of all target lesions  
• PR = ≥ 30% decrease in the sum of the longest diameter of target lesions  
• Overall Response (OR) = CR + PR  
• Progressive disease (PD) = 20% increase in the sum of the longest diameter of target 
lesions, and/or the appearance of one or more new lesion(s)  
• Stable disease (SD) = Small changes that do not meet any of the above criteria  
Time Frame:  up to 18 months  
3.  Outcome Title:  Progression-free Survival (PFS)  
Outcome Measure Description:  Progression-free survival (PFS) means the subject is 
alive without return or relapse of the tumor.  The outcome is defined as the number of 


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days to either progressive disease as defined per RECIST v1.1 or death, by each 
participant’s final infigratinib dose level, and reported as the median PFS with full range.  
RECIST criteria are:  
• CR = Disappearance of all target lesions  
• PR = ≥ 30% decrease in the sum of the longest diameter of target lesions  
• Overall Response (OR) = CR + PR  
• Progressive disease (PD) = 20% increase in the sum of the longest diameter of target 
lesions, and/or the appearance of one or more new lesion(s)  
• Stable disease (SD) = Small changes that do not meet any of the above criteria  
Time Frame:  Up to 2 years.  
4.  Outcome Title:  Clinical Benefit  
Outcome Measure Description:  Clinical benefit will be assessed as achieving a 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR) ; 
Partial Response (PR); or Stable Disease (SD).  The outcome will be reported as the 
number of subjects by each participant’s final infigratinib dose level that achieve a CR; 
PR; or SD, within 6 months of starting treatment.  The outcome will be reported by 
treatment and dose level as a number without dispersion.  RECIST criteria are:  
• CR = Disappearance of all target lesions  
• PR = ≥ 30% decrease in the sum of the longest diameter of target lesions  
• SD = Small changes that do not meet any of the above criteria  
• Progressive disease (PD) = 20% increase in the sum of the longest diameter of target 
lesions, and/or the appearance of one or more new lesion(s)  
• SD = Small changes that do not meet any of the above criteria  
Time Frame:  up to 6 months  
11. 
REGULATORY CONSIDERATIONS  
11.1 
Institutional Review of Protocol  
This study will be conducted under IND 147595 for infigratinib (pre-assigned).  Infigratinib was 
approved by FDA as Truseltiq pursuant the Accelerated Approval regulations on 28 May 2021 
for the indication of previously-treated, unresectable, locally-advanced or metastatic 
cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other 
rearrangement, in adults 
The protocol, the proposed informed consent and all forms of subject information related to the 
study (eg, advertisements used to recruit subjects) will be reviewed and approved by the 
Stanford IRB and Stanford Cancer Institute Scientific Review Committee (SRC).  Any changes 
made to the protocol will be submitted as a modification and will be approved by the IRB prior to 
implementation.  The Protocol Director will disseminate the protocol amendment information to 
all participating investigators.  


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11.2 
Data Sharing with Collaborators   
Distributor QED Therapeutics expects to share data from this study with the Helsinn Group 
(collaborator/partner).  
11.3 
Data and Safety Monitoring Plan  
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the 
monitoring entity for this study.  The DSMC will audit study-related activities to determine 
whether the study has been conducted in accordance with the protocol, local standard operating 
procedures, FDA regulations, and Good Clinical Practice (GCP).  This may include review of the 
following types of documents participating in the study:  regulatory binders, case report forms, 
eligibility checklists, and source documents.  In addition, the DSMC will regularly review serious 
adverse events and protocol deviations associated with the research to ensure the protection of 
human subjects.  Results of the DSMC audit will be communicated to the IRB and the 
appropriate regulatory authorities at the time of continuing review, or in an expedited fashion, as 
needed.  
11.4 
Data Management Plan  
The Protocol Director, or designee, will prepare and maintain adequate and accurate subject 
case histories with observations and data pertinent to the study.  Study specific Case Report 
Forms (CRFs) will document treatment outcomes for data analysis.  Case report forms will be 
created in the Stanford Research Electronic Data Capture (REDCap) and will be maintained by 
the Protocol Director, co-Protocol Director, and clinical research coordinator team.  All subjects 
will be registered in the OnCore database, allowing the Stanford SRC to judge the aggregate 
accrual and stopping rules for the study.  
12. 
STATISTICAL CONSIDERATIONS  
12.1 
Statistical Design and Sample Size Determination  
Statistical analyses of this non-randomized, phase 1B study will be primarily descriptive in 
nature.  Formal statistical methods will not be used to determine the number of subjects per 
cohort/dose level in this phase 1B study.  Summary statistics for discrete variables will be 
provided as frequencies and for continuous variables as the mean, standard deviation, median, 
and ranges.  
Cohort 1 will utilize the combination of tamoxifen and infigratinib at 3 infigratinib dose levels 
(125 mg;  100 mg;  and 75 mg).  This combination may play a role in the future development of 
infigratinib for hormone receptor-positive breast cancer, necessitating the establishment of their 
safety.  For example, tamoxifen and infigratinib might be used in the early-stage, (neo)adjuvant 
setting as well as the late-stage, metastatic setting.  Therefore, the design is based on patient 
resources and current drug development.  
12.2 
Interim analyses 
There will be no additional statistical stopping rules other than the 3+3 design rule for Cohort 1 
as described in Section 2.5, and there will be no planned interim analysis.  


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12.3 
Descriptive Statistics and Exploratory Data Analysis 
The exploratory elements described in Section 1.3 will be included in the descriptive statistics 
and exploratory data analyses. 
12.4 
Primary Safety Analysis  
Cohort 1 (infigratinib plus tamoxifen) will follow the 3+3 design evaluating 3 infigratinib doses 
levels, starting at 100 mg infigratinib 3 weeks on/1 week off) and moving to, if needed, 75 mg or 
125 mg infigratinib 3 weeks on/1 week off.  Given the nature of this cohort to be a safety run-in 
and the limited number of available subjects for this population, intra-subject dose-escalation 
will be allowed.  The risk with intra-subject dose-escalation is that a dose may be declared 
overly toxic when the toxicities should be attributed to the number of cycles rather than the 
dose, but it is believed this is a conservative approach focused on subject safety.  
Initially, 3 subjects will be treated at 100 mg for 2 cycles.  If there are no DLTs observed in a 
subject at 100 mg after 2 cycles, the subject will escalate to 125 mg for 2 additional cycles.  If 
1 DLT is observed at 100 mg, an additional 3 subjects will be treated at 100 mg.  If 
2 or more DLTs are observed at 100 mg, an additional 3 subjects will be treated at 75 mg.  If 
1 DLT is observed at 75 mg, an additional 3 subjects will be treated at 75 mg.  If no DLTs are 
observed in the first 3 subjects at 100 mg, but 1 DLT is observed at 125 mg, an additional 
3 subjects will be treated at 125 mg.  If 2 or more DLTs are observed at 125 mg, Cohort 1 will 
close.  If a dose achieves no DLTs in 3 subjects after 2 cycles or 1 DLT in 6 subjects after 
2 cycles, that dose will be declared safe for use in the main phase 2 trial. 
If a subject withdraws prior to the completion of the first 2 cycles of therapy without having 
experienced a DLT, an additional subject will be enrolled at that dose level.  
12.5 Secondary Safety Analysis  
The secondary safety analysis relates to the incidence of treatment-emergent adverse events 
(TEAEs).  TEAEs are those with initial onset or increasing in severity after the first dose of study 
treatment.  TEAEs will be graded by the investigator according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0 and coded using the Medical Dictionary for 
Regulatory Activities (MedDRA).  The number and percentage of subjects who experienced any 
AE, serious AE (SAE), treatment-related AE, and treatment-related SAE will be summarized 
according to worst toxicity grades.  The summaries will present AEs both on the entire study 
period and by cycle (Cycle 1 and Cycles beyond 1) in Cohort 1.  
Laboratory Test Abnormalities  
The number and percentage of subjects who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade observed for each laboratory assay.  The 
analyses will summarize laboratory tests both on the entire study period and by cycle (Cycle 1 
and Cycles beyond 1).  For laboratory tests without CTCAE grade definitions, results will be 
categorized as normal, abnormal, or not done.  


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12.6  Efficacy Analysis  
Tumor response will be presented in the form of subject data listings that include, but are not 
limited to:  
 
The classified integrative subtype (IC2 or IC6)  
 
Received (maximum) dose  
 
Overall tumor response at each imaging assessment point  
 
Best overall response  
In addition, disease progression date, death date, date of first response, and last tumor 
assessment date will be listed, together with progression-free survival.  A Kaplan-Meier plot will 
be created for progression-free survival overall, for IC2-classified tumors separately, and for 
IC6-classified tumors separately. 
12.7 
Analysis Population  
All subjects who received at least one dose of the study drug (infigratinib) will be analyzed for 
the safety and efficacy outcomes outlined in sections 12.4;  12.5;  and 12.6.  
12.8  Accrual Considerations  
There are approximately 600 new breast cancer patients seen annually at the Stanford Cancer 
Institute, an estimated 50 percent metastatic and 60% HR-positive, HER2-negative.  Based on 
METABRIC, we estimate that approximately 5% of HR-positive, HER2-negative tumors are 
integrative subtype 2 and 5% are integrative subtype 6. 2,3  We thus anticipate approximately 
20 eligible subjects per year, adequate for the accrual goals.  If accrual unexpectedly falls short, 
additional clinical sites may be added to the study.  
12.9 
Criteria for future studies  
If an MTD for infigratinib in combination with tamoxifen is identified with an acceptable number 
of DLTs (see Section 12.4), the combination will be deemed acceptable for future studies in this 
biomarker-selected population of advanced breast cancer.  Should this combination prove safe, 
the study team is planning additional studies to assess efficacy in multiple populations of breast 
cancer subjects whose tumors harbor FGFR pathway alterations.  


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APPENDICES  
APPENDIX A:  List of prohibited medications and substances 
Category 
Drug Names 
Strong inhibitors of CYP3A4 
clarithromycin, conivaptan, fluconazole, fluvoxamine, indinavir, 
itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, 
nefazodone, nelfinavir, norfloxacin, posaconazole, ritonavir, 
saquinavir, telithromycin, voriconazole  
  
grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, 
star fruits, pomelos, Seville oranges or products containing 
juice of these fruits   
Strong inducers of CYP3A4 
avasimibe, carbamazepine, nevirapine, phenobarbital, 
phenytoin, pioglitazone, primidone, rifabutin, rifampin, St.  
John's wort, troglitazone 
Medications which increase 
serum phosphorus and/or 
calcium 
calcium, parathyroid hormone, phosphate, vitamin D (including 
multivitamins containing vitamin D) 
Medications with established 
potential for QT prolongation or 
TdP 
amiodarone, anagrelide, arsenic trioxide, astemizole (off US 
market), azithromycin, bepridil (off US market), chloroquine, 
chlorpromazine, cisapride (off US market), citalopram, 
clarithromycin, cocaine, disopyramide, dofetilide, domperidone 
(not on US market), dronedarone, droperidol, erythromycin, 
escitalopram, flecainide, halofantrine, haloperidol, ibutilide, 
levofloxacin, levomethadyl (off US market), mesoridazine (off 
US market), methadone, moxifloxacin, pentamidine, pimozide, 
probucol (off US market), procainamide (oral off US market), 
quinidine, sevoflurane, sotalol, sparfloxacin (off US market), 
sulpiride (not on US market), terfenadine (off US market), 
thioridazine, vandetanib 
Abbreviations:  CYP – cytochrome P;  TdP – Torsades de Pointes;  US – United States.  


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APPENDIX B:  List of drugs to be used with caution while on study  
 
Category 
Drug Names 
CYP3A substrates with narrow 
therapeutic index 
alfentanil, cyclosporine, diergotamine, dihydroergotamine, 
ergotamine, fentanyl, sirolimus, tacrolimus, terfenadine, 
warfarin sodium or any other coumadin-derivative 
anticoagulants, direct thrombin inhibitors (eg, argatroban), and 
Factor Xa inhibitors (eg, rivaroxaban) 
Moderate inhibitors of 
CYP3A4 
amprenavir, aprepitant, atazanavir, cannabinoids, casopitant, 
cimetidine, ciprofloxacin, darunavir, diltiazem, fosamprenavir, 
imatinib, metronidazole, Schisandra sphenanthera, sertraline, 
suboxone, tofisopam, verapamil, zafirlukast 
Moderate inducers of CYP3A4 bosentan, cotrimoxazole, efavirenz, etravirine, ethosuximide, 
genistein, metyrapone, mexiletine, modafinil, nafcillin, 
talviraline, tipranavir 
Medications which alter the pH 
of the GI tract a,b 
antacids, H2antagonists (eg, ranitidine), proton-pump inhibitors 
(eg, omeprazole) 
Medications that have possible 
risk of TdP/QT prolongation 
alfuzosin, amantadine, atazanavir, chloral hydrate, clozapine, 
dolasetron, eribulin, famotidine, felbamate, fingolimod, 
foscarnet, fosphenytoin, gatifloxacin, gemifloxacin, granisertron, 
iloperidone, indapamide, isradipine, lapatinib, lithium, moexipril, 
nicardipine, nilotinib, octreotide, ofloxacin, ondansetron, 
oxytocin, paliperidone, pasireotide, quetiapine, ranolazine, 
risperidone, roxithromycin, sertindole, sunitinib, tamoxifen, 
tizanidine, vardenafil, venlafaxine, ziprasidone 
Medications that have 
conditional risk of TdP/QT 
prolongation 
amitriptyline, amisulpride, ciprofloxacin, clomipramine, 
desipramine, diphenhydramine, doxepin, fluoxetine, 
galantamine, imipramine, nortriptyline, paroxetine, protriptyline, 
sertraline, solifenacin, trazodone, trimethoprim-sulfa, 
trimipramine 
BCRP substrates 
atorvastatin, irinotecan, methotrexate, rosuvastatin, simvastatin, 
sulfasalazine, topotecan 
Abbreviations: BCRP, breast cancer resistance protein;  CYP, cytochrome p; F DA, Food and 
Drug Administration;  GI, gastrointestinal;  TdP, Torsades de Pointes  
a  Infigratinib should be dosed at least 2 hours before or 10 hours after dosing with a gastric 
protection agent.  
b  If possible, proton pump inhibitors should be avoided due to their long pharmacodynamic 
effect and replaced with H2 antagonists or antacids.  
 


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APPENDIX C:  RECIST v1.1  
Measurable Lesions  
 
Lesions that can be accurately measured in at least one dimension.  
 
Lesions with longest diameter twice the slice thickness and at least 10 mm or greater when 
assessed by CT or MRI (slice thickness 5 to 8 mm).  
 
Superficial lesions with longest diameter 10 mm or greater when assessed by caliper.  
 
Malignant lymph nodes with the short axis 15 mm or greater when assessed by CT.  
NOTE:  The shortest axis is used as the diameter for malignant lymph nodes, longest axis for all 
other measurable lesions.  
Non-measurable disease  
Non-measurable disease includes lesions too small to be considered measurable (including 
nodes with short axis between 10 and 14.9 mm) and truly non-measurable disease such as 
pleural or pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, 
lymphangitic involvement of skin or lung, clinical lesions that cannot be accurately measured 
with calipers, abdominal masses identified by physical exam that are not measurable by 
reproducible imaging techniques.  
 
Bone disease:  Bone disease is non-measurable with the exception of soft tissue 
components that can be evaluated by CT or MRI and meet the definition of measurability at 
baseline.  
 
Previous local treatment:  A previously irradiated lesion (or lesion subjected to other local 
treatment) is non-measurable unless it has progressed since completion of treatment.  
Normal sites  
 
Cystic lesions:  Simple cysts should not be considered as malignant lesions and should not 
be recorded either as target or non-target disease.  Cystic lesions thought to represent 
cystic metastases can be measurable lesions, if they meet the specific definition above.  
If non-cystic lesions are also present, these are preferred as target lesions.  
 
Normal nodes:  Nodes with short axis < 10 mm are considered normal and should not be 
recorded or followed either as measurable or non-measurable disease.  
RECORDING TUMOR ASSESSMENTS  
All sites of disease must be assessed at baseline.  Baseline assessments should be done as 
close as possible prior to study start.  For an adequate baseline assessment, all required scans 
must be done within 28 days prior to treatment and all disease must be documented 
appropriately.  If baseline assessment is inadequate, subsequent statuses generally should be 
indeterminate.  
Target lesions  
All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total, representative 
of all involved organs, should be identified as target lesions at baseline.  Target lesions should 


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be selected on the basis of size (longest lesions) and suitability for accurate repeated 
measurements.  Record the longest diameter for each lesion, except in the case of pathological 
lymph nodes for which the short axis should be recorded.  The sum of the diameters (longest for 
non-nodal lesions, short axis for nodal lesions) for all target lesions at baseline will be the basis 
for comparison to assessments performed on study.  
 
If two target lesions coalesce, the measurement of the coalesced mass is used.  If a large 
target lesion splits, the sum of the parts is used.  
 
Measurements for target lesions that become small should continue to be recorded.  If a 
target lesion becomes too small to measure, 0 mm should be recorded if the lesion is 
considered to have disappeared; otherwise, a default value of 5 mm should be recorded.  
NOTE:  When nodal lesions decrease to < 10 mm (normal), the actual measurement should still 
be recorded.  
Non-target disease  
All non-measurable disease is non-target.  All measurable lesions not identified as target lesions 
are also included as non-target disease.  Measurements are not required but rather 
assessments will be expressed as ABSENT, INDETERMINATE, PRESENT/NOT INCREASED, 
INCREASED.  Multiple non-target lesions in one organ may be recorded as a single item on the 
case report form (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’).  
OBJECTIVE RESPONSE STATUS AT EACH EVALUATION.  
Disease sites must be assessed using the same technique as baseline, including consistent 
administration of contrast and timing of scanning.  If a change needs to be made the case must 
be discussed with the radiologist to determine if substitution is possible.  If not, subsequent 
objective statuses are indeterminate.  
Target disease  
 
Complete Response (CR):  Complete disappearance of all target lesions with the exception 
of nodal disease.  All target nodes must decrease to normal size (short axis < 10 mm).  All 
target lesions must be assessed.  
 
Partial Response (PR):  Greater than or equal to 30% decrease under baseline of the sum 
of diameters of all target measurable lesions.  The short diameter is used in the sum for 
target nodes, while the longest diameter is used in the sum for all other target lesions.  All 
target lesions must be assessed.  
 
Stable:  Does not qualify for CR, PR or Progression.  All target lesions must be assessed.  
Stable can follow PR only in the rare case that the sum increases by less than 20% from the 
nadir, but enough that a previously documented 30% decrease no longer holds.  
 
Objective Progression (PD):  20% increase in the sum of diameters of target measurable 
lesions above the smallest sum observed (over baseline if no decrease in the sum is 
observed during therapy), with a minimum absolute increase of 5 mm.  
 
Indeterminate:  Progression has not been documented; and  
o One or more target measurable lesions have not been assessed; or  


A Phase 1B Study of Infigratinib in Combination with Tamoxifen in  
Hormone Receptor-positive, HER2-negative, FGFR-altered Advanced Breast Cancer  
IRB-53650 Version 11  
Page 71 of 72 
11 November 2021 
o Assessment methods used were inconsistent with those used at baseline; or  
o One or more target lesions cannot be measured accurately (eg, poorly visible unless due 
to being too small to measure); or  
o One or more target lesions were excised or irradiated and have not reappeared or 
increased.  
Non-target disease  
 
CR:  Disappearance of all non-target lesions and normalization of tumor marker levels.  All 
lymph nodes must be ‘normal’ in size (< 10 mm short axis).  
 
Non-CR/Non-PD:  Persistence of any non-target lesions and/or tumor marker level above 
the normal limits.  
 
PD:  Unequivocal progression of pre-existing lesions.  Generally, the overall tumor burden 
must increase sufficiently to merit discontinuation of therapy.  In the presence of SD or PR in 
target disease, progression due to unequivocal increase in non-target disease should be 
rare.  
 
Indeterminate:  Progression has not been determined and one or more non-target sites were 
not assessed or assessment methods were inconsistent with those used at baseline.  
New Lesions  
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example, due to its small size, continued assessment will clarify the etiology.  If 
repeat assessments confirm the lesion, then progression should be recorded on the date of the 
initial assessment.  A lesion identified in an area not previously scanned will be considered a 
new lesion.  
Supplemental Investigations  
If CR determination depends on a residual lesion that decreased in size but did not disappear 
completely, it is recommended the residual lesion be investigated with biopsy or fine needle 
aspirate.  If no disease is identified, objective status is CR.  
If progression determination depends on a lesion with an increase possibly due to necrosis, the 
lesion may be investigated with biopsy or fine needle aspirate to clarify status. 


A Phase 1B Study of Infigratinib in Combination with Tamoxifen in  
Hormone Receptor-positive, HER2-negative, FGFR-altered Advanced Breast Cancer  
IRB-53650 Version 11  
Page 72 of 72 
11 November 2021 
Objective Response Status at each Evaluation 
Target Lesions 
Non-target Lesions 
New Lesions Objective status 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Indeterminate or Missing 
No 
PR 
PR 
Non-CR/Non-PD, Indeterminate, or Missing 
No 
PR 
SD 
Non-CR/Non-PD, Indeterminate, or Missing 
No 
Stable 
Indeterminate or 
Missing 
Non-PD 
No 
Indeterminate 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
 

ICF_000.pdf: 
 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 1 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
STANFORD CONSENT FORM with HIPAA  
COHORT 1 – Infigratinib plus Tamoxifen  
Are you participating in any other research studies?   _____ Yes   _____No 
CONCISE SUMMARY  /  INTRODUCTION TO RESEARCH STUDIES 
This section is called the Concise Summary, and is intended to give you important 
information that will help you make an informed decision about whether or not to 
participate in this research study. 
• You are invited to voluntarily participate in a research study of infigratinib.  The 
part of the study you are invited to participate in is Cohort 1 evaluating infigratinib 
plus tamoxifen.  
• You were selected as a possible participant in this study because you have 
advanced breast cancer with certain characteristics known as “hormone 
receptor-positive,” and “HER2-negative.”  
o “Advanced” means your breast cancer spread outside of the breast and local 
lymph nodes, or cannot be readily removed by surgery.  Advanced cancers 
may be hard to treat.  
o “Hormone receptor-positive” means that the cancer expresses receptors for a 
female sex hormone, ie, either estrogen and/or progesterone.  
o “HER2-negative” means that there is a change in one of your genes that may 
affect the fibroblast growth factor receptor (FGFR) pathway, which plays an 
important role in cancer.  
• Infigratinib is an experimental (“investigational”) therapy to be used in combination 
with FDA-approved chemotherapy agents to treat hormone receptor-positive, 
HER2-negative advanced breast cancer, and your consent to participate is 
requested.  Because this is a research study, infigratinib will be given to you only 
during this study and not after the study is over.  
• This research study is in addition to, and does not replace, your regular medical 
care.  Infigratinib will be added to your regular medical care.  
• The purpose of this research is to study if infigratinib, when used in combination 
with FDA-approved chemotherapy agents, has an acceptable safety profile.  This 
information may help improve patient care.  Your participation in this study will 
help answer the research question.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 2 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• Reasonably-foreseeable risks or discomforts include eye problems, loss or 
thinning of hair, inflammation inside the mouth, stomach or intestinal side effects, 
and high phosphorus and/or calcium in the blood.  More detailed information is 
provided later in this document, in the section “Possible Risks, Discomforts, and 
Inconveniences.”  
• If you take part in this study, you agree not to eat grapefruit, grapefruit juice, 
grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or 
products containing juice of these fruits within 7 days of starting treatment and 
through the entire treatment period.  
• If you take part in this study, you may have to take a phosphate-lowering agent 
such as sevelamer. 
• If you take part in this study, your blood and tissue specimens will be retained for 
future research use. 
• Alternatives to participation in this study is not to participate, ie, receive the same 
or different treatment, but without infigratinib.  You should be aware that there are 
other effective treatments that are available to you without participating in this 
research study.  By participating in this research study, you may be foregoing 
other treatment options known to provide clinical benefit for your cancer.   
• Ask any questions you wish about this study.  If you want, you may discuss this 
with your family, friends, or your other doctors.  You can have a copy of this 
document to discuss with them.  
• If you decide to participate, you can stop your participation at any time.  If you 
want to stop your participation in the study, tell the study doctor or anyone on the 
study team.  If you wish to withdraw your specimens from future research, you 
need to state this in writing.  
• If you stop your participation in the study, your medical care may be compromised.  
You should discuss this decision with the study doctors, who will help you identify 
alternate care.  
This document is to be used as a guide for a discussion between you and your 
Study Doctor and the study team.  This form, called an informed consent document, was 
designed to help you understand why this study is being done;  what part of the study is 
“research” or “experimental;”  what will be asked of you if you choose to participate;  
possible risks;  any inconveniences or discomforts you may experience;  and other 
important information.  This document is intended to provide the information that a 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 3 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
potential participant might want to have in order to make an informed decision about 
whether to participate in the research study.  If you have any questions or would like 
additional information, please ask the person obtaining consent or any other member of 
the study team.  
If you choose to participate, this form may also be helpful as a reference or reminder 
about your role in the study, and whom to contact if you have any questions at any time 
during your participation.  
If you decide to take part in this research study, you will be asked to sign this consent 
form before any study-related activities are performed.  You will receive a copy of the 
signed consent document for your records.  
PURPOSE OF RESEARCH 
The study team hopes to learn if infigratinib, a drug that targets the FGFR cancer 
pathway, can be safely added to current anti-hormonal therapies, specifically those 
including tamoxifen (Nolvadex or Soltamox).  
The use of infigratinib in this research study is investigational (“experimental”).  The word 
“investigational” means that infigratinib is not currently approved by the US Food and 
Drug Administration (FDA) for use in the United States to treat your type of breast cancer, 
but has been approved for research studies.  This study is being conducted under an 
application submitted to FDA, called an “Investigational New Drug Application” or “IND.”  
Infigratinib will be provided for this study by the drug manufacturer QED Therapeutics, 
Inc.  Tamoxifen (Nolvadex or Soltamox) are used in this study according to their 
FDA-approved labeling.  
Your doctor recommends hormonal therapy as the best treatment choice that is available 
to you at this time.  Your normal medical care for this type of breast cancer could include 
tamoxifen or possibly other FDA-approved agents.  Using current therapies, some 
patients with advanced solid tumors such as yours receive treatment benefit, but are not 
cured of their disease.   
Your normal medical care would also include medical exams, blood tests, and medical 
scans to check the status of your cancer such as positron emission tomography (PET);  
computed tomography (CT);  or magnetic resonance imaging (MRI) scans.  
If you decide to stop participating in this study, you should notify Jennifer Caswell-Jin, MD, at 
650-724-3250 or a study team member.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 4 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
This research study is looking for up to 12 people in each of 2 treatment groups, and then 
an additional 12 subjects at the end to gain experience with safety and statistical efficacy 
for up to a total of 33 people with breast cancer.  There will be up to 12 participants in 
your cohort, Cohort 1, infigratinib plus tamoxifen.  This study is being conducted at 
Stanford University only.  
VOLUNTARY PARTICIPATION  
Your participation in this study is entirely voluntary.  Your decision not to participate will 
not have any negative effect on you or your medical care.  You can decide to participate 
now, but withdraw your consent later and stop being in the study without any loss of 
benefits or medical care to which you are entitled.  
DURATION OF STUDY INVOLVEMENT  
The study schedule includes a screening period, which may take up to 21 days;  up to 
18 cycles of treatment (each cycle is about 28 days / 1 month);  and a follow-up period for 
30 days after the last study treatment, for a total of about 20 months.  You will continue to 
be monitored for more than 30 days after treatment ends, if you continue to have 
unresolved side effects from the drug.  After the first 18 cycles of treatment, additional 
treatment may be allowed in certain situations.  
PROCEDURES 
It may be harmful to enter this study while receiving some medications, therefore, you 
may need to stop taking certain medications.  Your Study Doctor will review your 
medications and provide you with specific instructions.  
Research studies are usually dividing into at least 3 parts, typically consisting of: 
1. Testing to see if you are eligible to participate in the study (“Screening”);   
2. Testing during study treatment to monitor your health and the effects of the study 
treatment (“Study Evaluation Procedures”);  and  
3. Testing after your treatment is complete (“Follow-up”).   
Testing/procedures for each of these parts are described separately below.  
Some of these examinations, tests, or procedures may be part of your regular medical 
care, and/or and may be done even if you do not join the study.  If you have had some of 
them recently, they may not need to be repeated.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 5 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Before you join this study, Dr. Caswell-Jin and/or the research study team will review this 
document with you, and ask you to sign this informed consent document.  After you have 
signed this document and received a signed copy, the study will begin with a 
Screening Visit.  
You are assigned to Cohort 1 (infigratinib plus tamoxifen).  Events and timepoints 
occurring during the study period are described in further detail on the following pages.  
Screening Visit 
If you choose to participate and sign this consent document, the first activity will be 
Screening.  During the Screening Visit, you will be asked to have the following tests and 
activities or assessments.  After the results of the screening tests are assessed, you may 
be registered to the study as a participant.  Study drug treatment can start within 7 days 
of study registration.  
General information:  Information about you, such as date of birth;  gender (sex);  and 
ethnic origin (“demographic information”)  
Medical history:  Your complete medical history will be reviewed, including:  
• Review of all medicines and/or supplements you are taking or have been taking  
• Questions about any medical symptoms you are having  
• Surgery and cancer history, including tumor diagnostic testing  
• Reproductive status  
Physical examination:  A complete physical exam will be performed, including:  
• Your vital signs, including height;  weight;  breathing rate;  heart rate;  blood 
pressure;  temperature;  and other measurements  
• General examination of your body systems, such as heart and lungs;  ear, nose, 
and throat;  skin;  muscles and joints;  stomach and gastrointestinal tract;  and 
nervous system  
• You will be asked how well you are able to perform normal daily living activities 
(such as bathing, driving, shopping, working, etc)  
Blood collection:  Blood collection will typically be from a vein in your arm, using a blood 
collection needle.  This is called venipuncture.  If you have an implanted venous access 
port, this may be used for blood collection.  Standard aseptic (clean) techniques will be 
used.  Up to about 3 tablespoons (45 mL) of blood will be collected for:  
• Serum pregnancy test (if you are a woman who can become pregnant).  The 
pregnancy test must be negative within 7 days before the 1st dose of the study drugs.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 6 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• Complete blood count (CBC) with differential, including red blood cells (RBC, 
oxygen-carrying cells):  white blood cells (WBC, infection-fighting cells);  platelets;  
and other blood components.  
• Serum chemistry, including a “Complete Metabolic Panel,” consisting of tests for 
blood chemicals that indicate how well your body and organs are working, and if you 
have any significant diseases.  
• Tumor-typing tests to determine if your tumor classifies as integrative cluster 2 (IC2) 
or 6 (IC6), based on the results of an FDA-approved test called FoundationOne 
(F1CDx).  
• Blood levels (about 0.6 tablespoons, 10 mL) of the DNA changes in your body.  This 
will be collected before you receive the first dose treatment with the study drug on 
Study Day 1, Day 15, as well as at the end of your treatment.  Some of these blood 
samples will be used for research tests, and some will be stored for future study.  
Urine collection:  Urine will be collected for standard tests for waste products 
(“urinalysis”) that indicate how well your body is working, and if you have any significant 
diseases.  A urine pregnancy test (if you are a woman who can become pregnant), may 
be substituted for a serum pregnancy test.  The pregnancy test must be negative within 
7 days before the 1st dose of the study drugs.  
Electrocardiogram (ECG or EKG):  An ECG scan will be performed according to 
standard practice to measure and record the electrical activity of your heart.  This 
assessment is performed entirely from outside the body, meaning you do not have to 
have an injection or incision (noninvasive).  An ECG scan is a non-radiation procedure.  
The procedure is called a 12-lead ECG because 12 wires will be attached to your chest 
near your heart, and at your wrists/arms and ankles/legs with adhesive pads.  You will 
be asked to lie still during the procedure.  A computer will make a recording of 
your heart’s electrical activity, which will tell doctors information about how well 
your heart is working.  The results of this test may be used in combination with other 
imaging procedures described below.  
Echocardiogram (ECHO) scan:  A transthoracic ECHO scan will be performed 
according to standard practice to evaluate your heart's function and structures.  This 
assessment is performed entirely from outside the body, meaning you do not have to 
have an injection or incision (noninvasive).  An ECHO scan is a non-radiation procedure, 
and is similar to the sonogram procedure a woman might have during pregnancy.  A 
microphone-like device called a transducer will send out ultrasound waves into your 
chest.  Like a dog whistle, ultrasound is too high for you to hear.  The ultrasonic 
sound waves “echo” off of the heart structures, and a computer converts the echoes into 
images.  Generally, no calming medications (sedation) or fasting are needed.  Tell the 
study team if you have any medical devices implanted, such as a pacemaker.  Electrodes 
will be attached to your skin to record the echoes.  The ECHO technician will place a gel 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 7 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
on your chest.  The technician will apply varying amounts of pressure with the transducer 
probe.  The amount of pressure should not be uncomfortable, but if it does, tell the 
technician.  
Eye exam:  An eye exam will be conducted, consisting of standard procedures for 
visual acuity testing;  slit lamp examination of the anterior eye segment;  intraocular 
pressure;  dilated fundoscopy;  and retinal optical coherence tomography (OCT).  
Additional examinations such as specular microscopy (that enables a magnified, direct 
view of the corneal epithelium) and corneal pachymetry may be performed as clinically 
indicated.  If significant eye problems are found, you will not be able to participate in this 
study. 
CT imaging for tumor assessment:  A radiologic evaluation (an “X-ray”), called a 
computed tomography (CT scan) with contrast, will be performed according to standard 
practice within 28 days before the expected 1st day of treatment.  The scan will be of 
your chest, abdomen, and pelvis, and is called a CT-CAP scan.  These scans look at 
the extent and activity of your cancer.  You may be asked to not drink or eat anything 
(“fast”) for several hours before the scan.  The scan appointment will take about 
30 to 60 minutes.  This baseline scan is part of your regular medical care for a patient 
with an advanced solid tumor.   
Tumor biopsy:  A specimen of tissue that is taken from your body for laboratory testing, 
such as from the tumor or skin, is called a “biopsy.”  A biopsy specimen will be 
collected, and may be obtained with a hollow needle (the specimen is called a needle or 
core biopsy);  scalpel;  a special cutting instrument called a “punch;”  or other 
appropriate cutting instrument.  There will be at least 2 tumor biopsies as part of this 
study:  one before starting treatment (either at the same time as, or in addition to, your 
diagnostic biopsy confirming eligibility) and one on treatment.  Tumor biopsies will be 
collected if the study doctors decide it is safe and possible, and will not be taken if they 
decide that there is more than minimal additional risk.  In addition to assessing the 
status of your cancer, this tumor specimen may be used for many research purposes, 
and may be stored for future studies.  Fresh tumor specimens can be used to create cell 
cultures that allow investigators to study drug response and tumor evolution in the lab 
using live cells.  For example, investigators can treat the cell culture with new 
combinations of drugs to see how the cells respond.  Tumor specimen can also be used 
to evaluate DNA, RNA, or protein patterns, including in response to treatment.  For 
example, investigators can look for ways that the tumor responds to the treatment that 
might suggest new combinations of treatment that could work better.  
• In addition, you may have tumor specimens from biopsies and surgeries you have 
undergone in the past stored at Stanford, or at another hospital.  You may also 
undergo additional biopsies or surgeries as part of your clinical care in the future.  If 
there are stored specimens available from these past or future procedures that is not 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 8 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
needed for your diagnostic purposes, the study team may obtain it for future research 
purposes to study the DNA, RNA, and/or proteins in the specimens.  Your samples 
and de-identified clinical information may be sent outside of Stanford for analysis.  By 
signing this consent form, you are providing authorization for release of stored tissue 
specimens from outside hospitals or institutions to our study team. 
Future Use of Private Information and/or Specimens 
Research using tissue, such as a specimen of your tumor and blood, is an important 
way to try to understand human disease.  This research study may include the testing 
and study of genes, also known as DNA, and related materials called RNA, proteins, 
and/or metabolites.  This type of testing is also called “genetic analysis” or called 
“pharmacogenomic research.”  Previously-collected tumor specimens may also be used 
for this.  You are being given this information because the Study Doctors want to save 
private information and/or specimens for future research.  
There are several things you should know before participating in this study and allowing 
your blood and tumor specimens to be studied.  This subject is complicated, and there 
are many considerations.  Ask for more information if you do not understand any part of 
this information.  
Genes are in every cell of your body.  Your genes were inherited from your 
biological parents and carry instructions for the body to grow, develop, and survive.  
Genes are made of a substance called DNA.  Most genes and DNA are identical among 
human beings, but there are small variations between different people.  These small 
genetic differences are why people have their own unique characteristics, such 
hair color, eye color, height, and other characteristics.  Some traits affected by genetics 
are not visible, such as why different people have different responses, including 
side effects, to the same drug, or are more likely to get certain diseases or conditions.  
The proteins in your body were determined by your genes, and control how your body 
works.  Differences in genes and therefore proteins can affect the way a disease 
develops, the way drugs act against the disease, or the way your body uses the drugs.  
The purpose of this type of research is to understand the cause of disease, such as 
cancer, or the body’s response to the treatments (such as safety findings or drug level 
patterns).  In this study, the genetic research is being done to try to: 
• Discover new and better ways of treating breast tumors that have FGFR gene 
changes, including to find out if the study drugs were effective against your cancer, 
why it was effective, and if there are any characteristics of the cancer that 
predicted whether or not the drugs would be effective.  
• Why some tumors respond to therapy and others do not, and to identify markers of 
therapeutic resistance to certain treatments. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 9 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
You are not required to agree to provide the specimen for this genetic testing, but 
agreeing to provide this biopsy specimen is required to participate in this study.  If you 
do not wish to agree, the Study Doctor will discuss treatment options with you.   
The specimens collected in this study may be used for future research projects, 
including projects that are undetermined and may include “full genome sequencing” (ie, 
all your genes).  The results of future studies could trigger the need to test or re-test the 
genetic research specimens;  therefore, the specimens and data generated from them 
will be held by the sponsor or their partners for many years.  These specimens, and the 
data generated from them, may be shared with other researchers or entered into 
databases, provided confidentiality is upheld (you are not identified).  The information in 
these databases may be kept forever, however, information that could directly identify 
you will not be included in these databases.  
Genetic Information Data Sharing 
Information from analyses of your coded specimens and your coded information will be 
put into one of the National Institutes of Health (NIH) databases along with information 
from the other research participants, be shared broadly with the scientific community 
and be used for unspecified future research.  These databases will be accessible by the 
Internet.  Only anonymous information from the analyses will be put in a completely 
public database, available to anyone on the Internet, and may be used for any research 
purpose.  
No traditionally-used identifying information about you, such as your name;  address;  
telephone number;  or Social Security Number, will be put into the public database.  
While the public database will not contain information that is traditionally used to identify 
you, people may develop ways in the future that would allow someone to link your 
genetic or medical information in our databases back to you.  For example, someone 
could compare information in our databases with information from you (or a 
blood relative) in another database and be able to identify you (or your blood relative).  
It also is possible that there could be violations to the security of the computer systems 
used to store the codes linking your genetic and medical information to you.  Data 
cannot be retrieved once distributed to others. 
However, your privacy is very important to us and we will use safety measures to 
protect it.  Despite all of the safety measures that we will use, we cannot guarantee that 
your identity will never become known.  
Although you will be told the results of study tests that are part of your regular 
medical care, the genetic testing described here will not be used for decisions about 
your medical care, and there may be no results from this genetic research for 
many years, therefore the results of the genetic testing may not be given to you, your 
doctor, or any other staff at the study center.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 10 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Providing genetic information to others 
Sometimes patients have been required to furnish information from genetic testing for 
health insurance, life insurance, and/or a job.  A Federal law, the Genetic Information 
Nondiscrimination Act of 2008 (GINA), generally makes it illegal for health insurance 
companies, group health plans, and employers with 15 or more employees to 
discriminate against you based on your genetic information.  
Be aware that that GINA 2008 does not specifically protect you against 
genetic discrimination by companies that sell life insurance;  disability insurance;  or 
long-term care insurance.  
Handling of your Blood and Tissue Specimens 
Some of your specimens will be sent outside of Stanford for analysis.  Other parts of 
your specimens and the data from them will be stored at Stanford, using a unique 
subject identifier, called an OnCore subject number that is associated with the study 
and linked to your personal identifiers, such as your name and medical record 
number (MRN).  Only authorized personnel at Stanford will be able to associate you 
with the unique subject identifier (OnCore number). 
Because the specimens are linked to your personal health identifiers (PHI), you have 
the right to withdraw consent for the usage of these samples at any time.  The 
investigators might retain the specimens as part of your routine clinical care, but the 
specimens will not be used for additional research.   
Any of your tissue that is used in research may result in new products, tests or 
discoveries.  In some instances, these may have potential commercial value and may 
be developed and owned by the Investigators, Stanford University and/or others.  
However, donors of tissues do not retain any property rights to the materials.  
Therefore, you would not share in any financial benefits from these products, tests or 
discoveries. 
Your specimens and anonymized data information may be sent outside of Stanford for 
analysis.  “Anonymized” means that the specimens and data will not have your name 
and identification on them, but they could be re-identified.  
Women of Childbearing Potential 
Women of childbearing potential must be receiving a contraception treatment called 
luteinizing hormone (LH)-releasing hormone agonist (such as goserelin acetate or 
leuprolide acetate) initiated at least 28 days prior to study enrollment.   


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 11 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Study Treatment Period 
Treatment administration  
During the study treatment period, treatment will be administered as 28-day cycles 
(4 weeks).  Your study visits will be on Day 1 of each cycle, except there will be extra 
study visits on Cycle 1 Day 4, Cycle 1 Day 15, and Cycle 2 Day 15.  The following is a 
treatment summary for Cohort 1. 
• Infigratinib daily by mouth at the assigned dose (125 or 100 or 75 mg).  
Infigratinib is provided as hard gelatin capsules.  Monthly treatment schedule is 
3 weeks of treatment, following by 1 week with no treatment. 
• Tamoxifen administration 20 mg/day by mouth continuously starting on Day 1, 
4 hours after infigratinib.  Tamoxifen is provided as a pill.   
Tests and procedures 
The following tests and procedures will be performed at your clinical visits.  Not every 
test or procedure will be conducted at every visit.  
Medical history:  Your medical history will be updated as described above.  You will be 
asked about all the medications that you are taking, and if you have had any adverse 
medical experiences.  
Physical examination:  A physical exam as described above.  
Blood collection:   Blood will be collected as described above for evaluations and 
research tests.  Up to about 4 tablespoons (60 mL) of blood will be collected.  If you are a 
female of childbearing potential, the pregnancy test will be repeated on Day 1 of Cycle 1 
before you start treatment and if a potential pregnancy is suspected.  
Electrocardiogram (ECG or EKG):  As described above, on Day 1 (± 3 days) of 
Cycles 2, 4, 6, then Day 1 (± 3 days) of every 6th cycle.  
Echocardiogram (ECHO):  As described above, on Day 1 (± 3 days) of Cycle 2.  
Eye exam:  As described above, on Day 1 (± 14 days) of Cycles 2, 3, 4, 6 then on 
Day 1 (± 14 days) of every 3rd cycle. 
Tumor biopsy:  A 2nd tumor biopsy will be performed, as described above, on Day 15 
(± 3 days) of Cycle 1.  Any other time while on treatment is also acceptable. 
CT imaging for tumor assessment:  A CT-CAP as described above will be performed 
on Day 1 (± 7 days) of Cycle 3, then on Day 1 (± 7 days) of every other cycle (every 
2 cycles).  After 12 months of therapy, this can be spaced out to every 12 weeks (3 
cycles) at the Investigator’s discretion.   


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 12 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Adverse event monitoring will be performed as part of the procedures described 
above.  During the treatment period, the Study Doctors will monitor you for any potential 
side effects.  If the side effects are severe, the Study Doctors may temporarily stop 
study medication; change the dosage of your study medication; or withdraw your 
medication completely.  
If, at any time, you have any symptom; side effect; or injury affecting you physically or 
mentally during the study, you should tell the Study Doctors or nurses right away, 
even if you do not think it was caused by the study medication.  
If you have to go to the hospital for any reason, please tell the hospital staff that you are 
participating on a research study, and give them the contact information for the 
study team.  You may be provided with a card with the study team contact information. 
Study Follow-up Period  
When the decision to discontinue your treatment is made by you and/or your doctor, 
and approximately 30 days after your treatment is complete, the following tests and 
procedures will be conducted. 
Medical history:  As described above.  You will be asked about all the medications that 
you are taking, and if you have had any adverse medical experiences.  
Physical examination:  A physical exam as described above.  
Blood collection:   Blood will be collected as described above for evaluations and 
research tests.  This will be done one time at the discontinuation of your treatment.  If 
you are a female of childbearing potential, the pregnancy test will will be done one time 
at the discontinuation of your treatment.  
Electrocardiogram (ECG or EKG):  As described above.  This will be done one time at 
the discontinuation of your treatment. 
Echocardiogram (ECHO):  As described above.  This will be done one time at the 
discontinuation of your treatment.  
Eye exam:  As described above.  This will be done one time at the discontinuation of 
your treatment. 
CT imaging for tumor assessment:  A CT-CAP as described above will be performed 
one time at the discontinuation of your treatment if they were not done in the previous 4 
weeks. 
Adverse event monitoring will be performed as part of the procedures described 
above during the follow-up period.   


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 13 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
PARTICIPANT RESPONSIBILITIES  
As a participant, your responsibilities include:  
• Follow the instructions of the Protocol Director and study team.  
• Be sure to tell the study team about all of your present and past diseases, 
allergies and any drugs or medications you have been or are taking.  
• Do not take additional medications (including over-the-counter medications or 
supplements) without consulting your study doctor.  This is for your safety.  
Additional medications include all prescription drugs, 
over-the-counter (OTC) drugs, herbal preparations, and nutritional 
supplements.  These may interact with the study drug infigratinib.  There are 
numerous medications that may interfere with the effect of the study drugs.  
Before starting the study treatments, while you are on the study, and for 
30 days after your last dose of study treatment, do not take any other 
medications, even if prescribed by another doctor, without discussing 
with the study doctors.  
• Do not consume grapefruit, grapefruit juice, grapefruit hybrids, Seville 
oranges, pomegranates, star fruits, pomelos, or any products containing the 
juice of these fruits.  
• Most people taking infigratinib will develop high phosphorus in the blood.  You 
must follow the study doctor’s instructions on avoiding high-phosphate foods 
(maintain a low phosphorus diet) and taking phosphate binder medications 
(eg, sevelamer).  
• It is important to tell your doctor about any pre-existing eye problems you 
have, as your doctor may decide to change your treatment.  If you experience 
any eye changes or problems, contact the study doctors or team immediately.  
It is important that you do not drive a car or work with machinery if you begin 
to experience any visual changes while on the study.  
• Ask questions as you think of them.  
• Tell the Protocol Director, or any Study Doctor or study team member if you change 
your mind about staying in the study.  
• Tell the Protocol Director, or any Study Doctor or study team member about any side 
effects, doctor visits, or hospitalizations that you may have.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 14 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• If you are a woman able to have children and are sexually-active with men, use 
barrier contraception (ie, diaphragm, cervical cap, male or female condom, 
spermicidal foam, sponges or film) for intercourse while taking infigratinib and for 
3 months following the last dose of infigratinib.  You must use barrier contraception 
regardless of any other form of birth control you continue to use.  
• If you are a sexually-active man, use a condom during intercourse while taking 
infigratinib and for 3 months following the last dose of infigratinib.  Men must use a 
condom even if they have had a vasectomy, and even during intercourse with a male 
partner.  
• Tell the Protocol Director, or any Study Doctor or study team member if you believe 
you might be pregnant or have gotten your partner pregnant.  If you are a woman and 
experience a miss in menses cycle (“miss your period”), you must inform the 
Protocol Director or study team. 
• Keep your study appointments.  If it is necessary to miss an appointment, please 
contact the Protocol Director, or any Study Doctor or study team member to 
reschedule as soon as you know you will miss the appointment.  
• Take the Study Drugs as instructed.  
• Maintain control of the Study Drugs, and keep them in a safe place where children 
cannot access them.  Follow any additional storage instructions that you are provided 
with.  
WITHDRAWAL FROM THE STUDY 
If you first agree to participate and then you change your mind, you are free to 
withdraw your consent and discontinue your participation at any time.  Your decision will 
not affect your ability to receive medical care for your disease and you will not lose 
any benefits to which you would otherwise be entitled.  
If you decide to withdraw your consent to participate in this study, you should notify 
Jennifer Caswell-Jin, MD, at 650-724-3250 or a study team member.  If you withdraw 
after starting treatment with the study drugs, your Study Doctor will need to check on your 
health status afterwards.  If you do not want the Study Doctor to check on your health 
status after withdrawing from the study, you should say so.  Upon your request to the 
Protocol Director, any remaining biological samples that have been collected from you 
will be destroyed.  However, any data collected before you withdrew will be retained and 
used to complete the research.  
To help you safely finish your participation in the study, the Study Doctors may ask you to 
have more tests and you will be asked to come into the clinic for an 
End-of-Treatment Visit within 14 days of stopping the Study Drugs.  The Study Doctor will 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 15 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
discuss your treatment options with you at this time.  If your participation in the study is 
ended, you must return all study-related supplies, including unused Study Drugs.  
If you withdraw from the study, or the study medication is stopped for any reason,  
• Your cancer may get worse.  
• To help you leave the study safely, the Study Doctors may ask you to have more 
tests.  
• The Study Doctors may also ask if you wish to take part in the follow-up portion of 
the study.  If you agree to continue with the follow-up portion of the study, information 
about your health will continue to be collected as described above in the Follow-up 
Procedures section.  
• The Study Doctor will discuss with you the different withdrawal decisions, including 
your options for continued treatment.  
• If your participation in the study ends, you must return all study-related supplies, 
including unused Study Drug.  
• Data and information from your participation may not be removed from the research 
study database and may continue to be used to complete the research analysis.  
This is discussed in more detail under the heading “Authorization To Use Your 
Health Information For Research Purposes” on the following pages.  
Your treatment in this study can continue until one of the following occurs:   
• You withdraw your agreement to continue to take part in this research study;  
• The Study Doctor withdraws you from the study, and the study medication is 
stopped, with or without your consent, for one or more of the following reasons:   
o Failure to follow the instructions of the Protocol Director and study team  
o The Study Doctor decides that continuing your participation could be harmful to 
you, or otherwise not in your best interest  
o Your cancer becomes worse (tumor progression)  
o If you have bad side effects during treatment, or if you or your doctor otherwise 
decide that the side effects are too severe or undesirable 
o You need treatment with drugs or procedures not allowed in the study  
o You have become pregnant;  intend to become pregnant;  or are nursing a child 
during this study 
o The study is stopped by the drug manufacturer, QED Therapeutics;  their 
collaborator the Helsinn Group;  the Study Doctor;  the Stanford Institutional 
Review Board (the IRB, a group of people who review the research to protect your 
rights), or by a regulatory agency such as the US FDA  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 16 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
o Other administrative reasons  
o Unanticipated circumstances  
When your participation in this study ends, you may be asked to return for a final visit to 
have some end-of-study evaluations or tests, or to allow medical information to be 
collected about your health after the trial treatment is stopped.  After you finish the study, 
or stop taking the Study Drugs for any other reason, you may continue to be checked 
regularly (physical exams;  blood tests;  tumor measurements;  X-rays;  other scans, etc) 
if you continue to have significant side effects from the treatment.  This is called 
follow-up.  Your Study Doctor will follow your progress, in accordance with good 
medical care, for as long as it is felt to be necessary by both you and the doctor, unless 
you ask otherwise.  Many if not all of these procedures will be part of your regular 
continued medical care.  In addition, further treatment outside the study will be discussed 
with you.  
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
This section describes the reasonably-foreseeable risks, discomforts, and 
inconveniences that you may experience while participating in this study.  These may 
make you sick, feel uncomfortable, or even harm you.  These deserve careful thought.   
You might experience negative effects related to the study drug while participating in the 
study.  All research participants taking part in the study will be watched carefully for any 
negative effects; however, the study team does not know all the effects that the study 
drug may have on you.  The study team may give you medicines to help reduce negative 
effects.  These effects may be mild or serious.  Many side effects go away when 
treatment is stopped, but in some cases, it is possible that the side effects could be 
serious, long-lasting, permanent, or may even be life threatening or fatal.  In addition, 
because this is a research study, there may be risks that are not yet known 
(“unforeseeable”).  You should discuss the side effects listed below with your study 
doctor before joining the study.   
If you have any questions, you should contact Jennifer Caswell-Jin, MD, at 650-724-3250 
or a study team member. 
The negative events that are the most likely to happen to you if you take part in this study 
are listed below.  The study drugs and procedures in this study may have risks that are 
not known at this time.  You must tell the Study Doctor or study team about all side 
effects that you have.  It is important that you report all symptoms and side effects that 
you experience as soon as they occur, whether or not you think they are caused by the 
study drug.  If you are not honest about your side effects, it may not be safe for you to 
stay in the study.  Your Study Doctor may give you medications to try to help lessen 
some of the side effects.  All patients in the study will be monitored for side effects.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 17 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
If you experience serious problems, you may be asked to return to the study center for 
more tests.  If you experience any of the following symptoms of an allergic reaction, 
contact the Study Doctor or the Study Team immediately.  An allergic reaction, if not 
treated promptly, can become life-threatening.  
• Difficulty breathing;  shortness of breath;  or wheezing  
• Swelling of the face, mouth, lips, gums, tongue or neck 
• Rash, hives, or blisters  
• Increased heart rate (a fast pulse or tachycardia)  
• Abnormal or increased sweating  
• Dizziness and fainting  
Potential side effects of infigratinib 
Infigratinib has been administered at the dose and schedule to be used in this study 
(up to 125 mg, 3 weeks on / 1 week off) to more than 400 people with advanced cancer.  
Some of the most important potential side effects to be aware of are: 
• High phosphorus in the blood.  Most people who take infigratinib (about 64%) will 
develop high phosphorus, and may need to go on a low phosphorus diet and/or 
take a phosphorus-lowering medicine called sevelamer to control their 
phosphorus level.  Most people who developed high phosphorus while on 
infigratinib did not have any associated symptoms, but high phosphorus can 
cause muscle or joint pains or cramps and other symptoms in some people.   
• High calcium in the blood.  This is less common than high phosphorus 
(approximately 14%), but can occur.  Most people who developed high calcium 
while on infigratinib did not have any associated symptoms, but high calcium can 
cause constipation, abdominal pain, nausea or vomiting, low appetite, and other 
symptoms in some people.  
• Eye problems.  About half of people taking infigratinib have eye effects.  All 
participants will undergo a detailed eye examination at the start of the study, after 
1 month, 2 months, 3 months, 5 months on therapy, and subsequently about 
every 3 months during the study.  If significant and/or persistent changes from 
baseline are found while you are on study, you may need to discontinue from the 
study.  It is important to tell your doctor about any pre-existing eye problems you 
have and visual changes that occur while taking infigratinib, as your doctor may 
decide to change or stop your treatment.  It is important that you do not drive a 
car or work with machinery if you begin to experience any visual changes while 
on the study. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 18 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Most of the eye problems on infigratinib were generally manageable.  The most 
common eye problems seen were dry eye (22%) and blurred vision (10%).  More 
serious eye problems can occur, in about 3% of people.  For example: 
o Less than 1% of people developed symptomatic cataract causing vision to be 
worse than 20/40. 
o Less than 1% of people developed corneal inflammation or a corneal ulcer, 
causing vision to be worse than 20/40. 
o Less than 1% of people developed vision worsening to worse than 20/40 that 
was caused by other reasons, ie, not caused by cataract or 
corneal inflammation. 
• Inflammation of the inside of the mouth (“stomatitis”).  This was seen in 37% of 
people taking infigratinib, and was severe (interfering with being able to eat or 
drink) in 5%. 
• Stomach or intestinal side effects.  36% developed constipation, 27% developed 
diarrhea, and 28% developed nausea at some point on therapy.  In most people, 
these side effects were manageable. 
• Hair loss or thinning.  27% of people noted this.  
Beyond the effects listed above, the following negative events occurred in at least 10% 
of the people who took infigratinib at the dose and schedule in this study.  For some of 
these effects, it is not clear if people developed these symptoms because of infigratinib, 
because of their cancer, or for some other reason: 
• Tired feeling (fatigue) (40%) 
• Decreased appetite (anorexia) (30%) 
• Dry mouth (23%) 
• Altered taste (21%) 
• Vomiting (21%) 
• Joint pain (17%) 
• Stomach pain (15%) 
• Trouble breathing (15%) 
• Weight loss (13%) 
• Hand/foot syndrome (palmar-plantar erythrodysaesthesia syndrome) (14%) 
• Dry skin (12%) 
• Fever (12%) 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 19 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• Back pain (12%) 
• Leg or arm pain (12%) 
• Cough (11%) 
• Nail disorder (13%) 
• Headache (11%) 
• Lack of energy (10%) 
• Nosebleeds (10%).  
Other less common side effects of uncertain relatedness that were observed in less 
than 10% of individuals include: 
• Eyelash changes (8%) 
• Loss of eyelashes (madarosis) (2%) 
• Shortness of breath (1%) 
• Cough (1%) 
• Pain while peeing (1%) 
• Acne (1%) 
• Inflamed colon (1%) 
• Temporary increase in the time it takes for the heart to recharge between beats 
(measured via electrocardiogram [ECG], and most often without symptoms (1%) 
• Painful and swollen gums (1%) 
• Anxiety (0.5%) 
• Abnormal deposit of calcium salts in body tissues and small blood vessels of the 
fat and skin tissues (calcinosis/calciphylaxis) (0.5%) 
There are also laboratory abnormalities that may occur.  Most of these would be 
detected by blood tests, would not cause any symptoms, and would be reversible.  In 
rarer cases, they could require stopping the drug or potentially even hospitalization.  
These laboratory abnormalities may indicate: 
• Worsening kidney function (24%) 
• Increased liver enzymes (16%) 
• Decreased red blood cell count, which can cause fatigue or shortness of 
breath (18%) 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 20 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• Decreased phosphorus, usually due to the medication given to treat increased 
phosphorus levels (13%) 
• Increased pancreas enzymes (11%) 
• Low sodium level (11%).  
• Decreased parathyroid hormone (1%) 
• Increased or decreased blood sugar (0.5 to 1%) 
• Decreased activity of the thyroid gland (hypothyroidism) (0.5%) 
Deaths during infigratinib treatment  
Of the 458 people who took infigratinib at the dose and schedule used in this study at 
the time of this report, there have been 2 deaths for reasons possibly-related to 
infigratinib.  One of these people died from a cardiac arrest and one died from a lack 
of blood flow to the intestines.  
Other risks from infigratinib: 
Since infigratinib is an investigational drug, there may be other risks that are unknown.   
It is important that you report all symptoms and side effects that you experience as 
soon as they occur, whether or not you think they are caused by the study treatment 
and whether or not you think they are serious.  
Potential side effects of sevelamer  
Sevelamer is likely to be administered while you are taking infigratinib, to help manage 
high phosphorus in the blood, a common side effect of infigratinib.  Sevelamer is an 
FDA-approved drug, and its drug package insert provides a complete listing of 
warnings and precautions. 
The most common adverse events of sevelamer include  nausea;  vomiting;  
stomach pain;  loss of appetite (anorexia);  upset stomach;  gas;  bloating;  diarrhea;  
constipation;  tired feeling (fatigue);  itching (pruritus);  and joint pain . 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 21 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Potential side effects of tamoxifen 
Tamoxifen is an FDA-approved drug, and its drug package insert provides a complete 
listing of warnings and precautions. 
The most common adverse events occurring in patients receiving tamoxifen are hot 
flashes, mood disturbances, vaginal bleeding, nausea, and fluid retention.  
Specific warnings for tamoxifen 
• Risk of uterine malignancy. 
• Risk of increased thromboembolic events – stroke, or blood clots in various areas 
of the body including the lungs (pulmonary embolism), gastrointestinal tract, 
kidneys, or legs (deep vein thrombosis). 
• Risk of liver cancer and liver abnormalities. 
• Tamoxifen can cause fetal harm when administered to a pregnant woman. 
In addition, there are other risks and possible discomforts you might experience from 
the study procedures.  The following discusses procedure risks related only to the 
research, and does not include risks of procedures that should be discussed as part of 
your regular medical care.  
• Allergic reactions:  All drugs have a potential risk of an allergic reaction, which if 
not treated promptly, could become life-threatening.  You should get medical help 
and contact the Study Doctors right away if you think you have any of the following 
symptoms of a serious allergic reaction:  trouble breathing, or swelling of the face, 
mouth, lips, gums, tongue or neck.  Other allergic reactions may include rash, hives, 
or blisters.  
• Blood draws:  A blood draw may cause fainting;  inflammation of the vein;  stinging, 
discomfort, or pain;  bruising;  discomfort;  redness;  burning;  swelling;  or bleeding at 
the site where the needle is placed to draw the blood.  There is a slight chance of 
infection.  You may feel dizzy or you may faint.  If you feel faint, you should 
immediately lie down to avoid falling.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 22 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
• Tumor biopsy:  The risk of a tumor biopsy depends on the size, type, and location 
of your cancer.  The most common side effects, which are usually minor, include 
pain, discomfort, bleeding, redness and swelling, scarring, bruising, and/or infection 
at the site where the biopsy needle is inserted, as well as fever.  You may 
experience dizziness or fainting.  Pain and discomfort can last for a couple of hours 
to a couple of days after the specimen is taken.  Significant bleeding and infection 
may occur, but are uncommon.  To reduce these risks, the site of the biopsy will be 
numbed and sterile techniques will be used.  Your doctor may give you antibiotics to 
prevent or treat any infection.  In extremely rare cases, an allergic reaction to the 
local anesthetic used to numb the biopsy site can occur.  Biopsies are routine 
procedures, and established institutional procedures will be followed.  You may be 
required to sign a separate informed consent form.  
• ECG:  Risks from an ECG can include skin irritation and/or a rash from the gel, or 
from wearing or removing the patches.  
• ECHO scan:  An ECHO scan is very similar to a sonogram, such as a pregnant 
woman might receive, and is considered very safe.  For some patients, having to lie 
still on the examination table for the length of the procedure may cause some 
discomfort or pain.  
• Radiologic imaging:  X-ray / CT scans.  A CT scan exposes you to radiation 
(discussed below).  When you are in the scanner, you may experience discomfort or 
anxiety due to be in the small space inside the machine, or from the loud noises the 
scanner makes.  If you become anxious or concerned in tight spaces, or from 
loud noises, tell the study team or technician before the scan.  You may receive a 
medication to calm you if you need help with this.  
• Radiologic imaging:  Radiation exposure from X-ray / CT scans.  This research 
study involves exposure to radiation from 2 Chest/Abdomen/Pelvis CT exams.  This 
radiation exposure is not necessary for your medical care and is for research 
purposes only.  The additional amount of radiation exposure is about 25 mSv, which 
is approximately equal to 50% of the limit that radiation workers (for example, a 
hospital X-ray technician) are allowed to receive in 1 year.  This amount of radiation 
involves minimal risk and is necessary to obtain the research information desired.  
• Radiologic imaging:  Injection of contrast agents:  A contrast agent or dye will be 
injected for the CT scans.  Following are the risks associated with injection of 
contrast agents.   
o Allergic reaction, which can be severe and/or life-threatening.   
o Kidney problems or kidney failure, especially if you are taking 
Glucophage (metformin, a common medicine for diabetes).    
o After the injection, there is a risk of pain, discomfort, or a burning sensation at the 
injection site; a flushing or warmth sensation; a salty or metallic taste in the 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 23 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
mouth; a brief headache; or nausea/vomiting.  nausea, flushing, warmth, and a 
salty taste.  These effects usually last for a few moments.   
o If you are a smoker or exposed to cigarettes or nicotine, you may experience 
spasms in the arteries of your heart.   
• Pregnancy / Reproductive Risk:  Because your treatment includes chemotherapy, 
there are risks to a fetus (unborn child) or the pregnant woman, even if it is the man 
participating in this study.  There is a risk that pregnancy could still result despite the 
responsible use of reliable method of birth control.  You must use barrier protection 
as outlined in “Participant Responsibilities”. Detailed information about preventing 
pregnancy is also provided in that section.  
• Women of childbearing potential:  If you believe you might be pregnant, even if 
you experience a menses cycle (“have your period”), you must inform the 
Protocol Director or study team immediately.  
• Genetic research risks:  This research involves genetic studies and information.  
Procedures have been put into place that are designed to make it very difficult for 
the results from genetic research to be linked to you.  However, even without your 
name or other identifiers, your genetic information is unique to you, and there is a 
remote possibility that someone could trace the information in a central database 
back, and identify you.  If a genetic disorder is discovered in your genes, there is a 
remote possibility that this information could become public and affect you or your 
family in an unfavorable way, including a possible risk of discrimination by employers 
or insurance providers.  
• Personal anxiety:  Following are some common concerns that research subjects 
may have.  
o You may be asked sensitive or private questions which you normally do not 
discuss.  It may be necessary to answer some of these questions related to your 
health and medical status.  
o You may feel embarrassed during the physical exam.  You may request that the 
physical exam be done by a clinician of the same gender.  
o You may be concerned about your personal information being revealed.  
Although the Study Team, NCI, NIH, and FDA do their best to protect your 
personal information, this cannot be absolutely guaranteed.  
• Other risks:  Since infigratinib is investigational (“experimental”) when taken alone 
or in combination with other medications, there may be other risks that are unknown 
(“unforeseeable”) at this time.  
It is important that you report all symptoms and side effects that you experience 
as soon as they occur, whether or not you think they are caused by the 
study drugs or the study procedures.  Contact Jennifer Caswell-Jin, MD at 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 24 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
650-724-3250 or the Study Team via the Nurse Coordinators at 650-498-6000 
(24 hours).  If you are unable to reach anyone at the number(s) listed above, and you 
feel you may need medical attention, call 911 or go to the nearest emergency room.  
POTENTIAL BENEFITS  
It is possible that your health or medical condition may improve because of your 
participation in this study.  The use of the study treatment, may help to treat your disease.  
However, there is no guarantee that you will benefit in this or any other way.  
Although you may not directly benefit from participation in this study,  information learned 
from this study may help other people in the future, including other people with cancer.  
We cannot and do not guarantee or promise that you will receive any benefits from this 
study.  
ALTERNATIVES 
You should be aware that there are other effective treatments that are available to you 
without participating in this research study.  By participating in this research study, you 
may be foregoing other treatment options known to provide clinical benefit for your 
cancer.  The Study Doctors will discuss with you the risks and benefits of these 
alternatives, including which other treatments might be suitable for you.  
You do not have to be in this study to receive treatment for your cancer.  Possible 
alternative treatments and side effects of these treatments depend on the characteristics 
of your cancer, and the stage and location of your cancer.  The effectiveness and side 
effects of other treatments may be different for different people.  Instead of taking part in 
this study, you may choose to:  
• Surgically remove the tumor.  
• Receive radiation therapy, but not as part of this study.  
• Receive treatment with other chemotherapy drugs, including those that have been 
approved for use in the US.  There are numerous treatments that may or may not be 
suitable for the specifics of your cancer.  The study doctor can discuss these with you.  
• Receive treatment with other drugs called targeted therapies, which recognize specific 
features of cancer, and focus the treatment effect on those cells.  There are numerous 
treatments that may or may not be suitable for the specifics of your cancer.  The 
study doctor can discuss these with you.   
• Receive surgery plus 1 or more of the above therapies.  There are specific names for 
the order in which this type of treatment is given.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 25 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
o Neoadjuvant treatment, which means to receive chemotherapy and/or radiation 
therapy before surgery.  Having one or both of these before surgery may help 
shrink the tumor, which may be easier to remove during the surgery.  
o Adjuvant treatment, which means having a surgery first, then receiving 
chemotherapy and/or radiation therapy.  The goal of adjuvant treatment is to kill 
any cancer cells that may be left in your body after the surgery.  Even if there is no 
visible sign of cancer cells, your physician may suggest adjuvant treatment to kill 
remaining microscopic cancer, as this lowers the risk that the cancer may come 
back or spread.  
• Participate in another research study with a different study drug or procedure.  
• While your type of cancer may be treatable with currently approved and available 
medications and procedures, another alternative is to receive only comfort care, also 
called “palliative care,” like painkillers.  These types of treatments do not treat your 
cancer (ie, “are not curative”), and only make you comfortable (“symptom relief;” pain 
reduction;  reduce tiredness, help with appetite problems or other problems caused by 
cancer).  If you think you might prefer comfort care, please discuss this with your 
family, friends, and doctor.  NOTE:  The Study Doctors do not recommend this 
decision for you at this time, although it is and will remain your decision.  
The Study Doctors will discuss with you the risks and benefits of these alternatives, 
including which other treatments might be suitable for you.  
If you decide that you do not wish to take part in this study and wish to pursue any of 
these, or other alternatives, this will not change your regular medical care or the other 
treatment choices in any way.  
PARTICIPANT’S RIGHTS 
You should not feel obligated to agree to participate.  Your questions should be answered 
clearly and to your satisfaction.  If you decide not to participate, tell the Protocol Director.  
You can also tell any other member of the study team. 
You will be told of any significant new information that is learned during the course of this 
research study, which might affect your condition or your willingness to continue 
participation in this study.  After you hear about this information, you have the right to 
withdraw from the program.  
If medically-relevant information about you or your test results that might affect your 
future treatment or your willingness to continue participation in this study is obtained, this 
information will be discussed with you.  
You will be told the results of tests that are part of your medical care, but you may not 
be told the results of the research tests, including any future research tests.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 26 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
ClinicalTrials.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by US Law.  This web site will not include information that can identify you.  
At most, the web site will include a summary of the results.  You can search this 
web site at any time.  
CONFIDENTIALITY 
Identifiers might be removed from identifiable private information and/or identifiable 
specimens and, after such removal, the information and/or specimens could be used for 
future research studies or distributed to another investigator for future research studies 
without additional informed consent from you.  
The results of this research study may be presented at scientific or medical meetings or 
published in scientific journals.  Your identity and/or your personal health information will 
not be disclosed except as authorized by you or as required by law.  However, there is 
always some risk that even de-identified information might be re-identified.  
Your research records may be disclosed outside of Stanford, including in computer 
databases and by other electronic methods, but you will only be identified by your unique 
study identifier, and not your name.  Information linking your study identifier to your name 
will be kept in a secure location at Stanford and access will be limited to the Study Doctor 
and authorized members of the Study Team.  
Patient information may be provided to federal and other regulatory agencies as required.  
The US FDA, for example, may inspect research records and learn your identity if this 
study falls within its jurisdiction.  
The purpose of this research study is to obtain data or information on the safety and 
effectiveness of infigratinib in combination with other chemotherapy agents;  the results 
will be provided to the drug manufacturer QED Therapeutics;  their collaborator the 
Helsinn Group; the Food and Drug Administration (FDA);  and other federal and 
regulatory agencies as required.  
CERTIFICATE OF CONFIDENTIALITY 
This research is covered by a Certificate of Confidentiality from the 
National Institutes of Health (NIH).  The researchers with this Certificate may not disclose 
or use information, documents, or biospecimens that may identify you in any federal, 
state, or local civil, criminal, administrative, legislative, or other action, suit, or proceeding, 
or be used as evidence, for example, if there is a court subpoena, unless you have 
consented for this use.  Information, documents, or biospecimens protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 27 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
except, if there is a federal, state, or local law that requires disclosure (such as to report 
child abuse or communicable diseases but not for federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings, see below);  if you have consented to the 
disclosure, including for your medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects.  
The Certificate cannot be used to refuse a request for information from personnel of the 
United States federal or state government agency sponsoring the project that is needed 
for auditing or program evaluation by National Cancer Institute (NCI), an institute of the 
US National Institutes of Health (NIH), which is funding this project or for information that 
must be disclosed in order to meet the requirements of the federal Food and Drug 
Administration (FDA).  You should understand that a Certificate of Confidentiality does 
not prevent you from voluntarily releasing information about yourself or your involvement 
in this research.  If you want your research information released to an insurer, medical 
care provider, or any other person not connected with the research, you must provide 
consent to allow the researchers to release it. 
The Certificate of Confidentiality will not be used to prevent disclosure for any purpose 
you have consented to in this informed consent document, such as research data in your 
medical record. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 28 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Authorization To Use Your Health Information  
For Research Purposes 
Because information about you and your health is personal and private, it 
generally cannot be used in this research study without your written 
authorization.  If you sign this form, it will provide that authorization.  The 
form is intended to inform you about how your health information will be 
used or disclosed in the study.  Your information will only be used in 
accordance with this authorization form and the informed consent form and 
as required or allowed by law.  Please read it carefully before signing it.  
What is the purpose of this research study and how will my health 
information be utilized in the study?  
The purpose of this research study is to learn about the safety and 
effectiveness of infigratinib in combination with chemotherapy, and to find 
the best dose of infigratinib in the combinations.  Information from this 
study will be submitted to the drug manufacturer QED Therapeutics and 
partner Helsinn Group, and international regulatory agencies including the 
FDA.  The results from this research study are expected to be presented at 
scientific or medical meetings or published in scientific journals.  You will 
not be personally identified in the publications, although 
representatives of the sponsor, FDA, and other international 
regulatory agencies may need to know who you are.  
Do I have to sign this authorization form? 
You do not have to sign this authorization form.  But if you do not, you will 
not be able to participate in this research study including receiving any 
research-related treatment.   
Signing the form is not a condition for receiving any medical care outside 
the study.  
If I sign, can I revoke it or withdraw from the research later?  
If you decide to participate, you are free to withdraw your authorization 
regarding the use and disclosure of your health information (and to 
discontinue any other participation in the study) at any time.  After any 
revocation, your health information will no longer be used or disclosed in 
the study, except to the extent that the law allows us to continue using your 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 29 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
information (eg, necessary to maintain integrity of research).  If you wish to 
revoke your authorization for the research use or disclosure of your health 
information in this study, you must write to:  
Jennifer Caswell-Jin, MD  
269 Campus Dr;  CCSR 1145C;  M/C 5769 
Stanford Cancer Institute;  Stanford University Medical Center 
Stanford, CA  94305  
What Personal Information Will Be Obtained, Used or Disclosed?  
Your health information related to this study, may be used or disclosed in 
connection with this research study, including, but not limited to identifiers 
such as your name and initials, address including ZIP code, 
phone numbers, dates including date of birth, age, biological gender 
(your sex), race, ethnicity, and other numbers or codes such as your 
unique study identifier that might identify you.  During the study, 
researchers will also obtain information about your health status, life-style 
choices, medical history, and medical diagnoses, including family 
medical history and allergies;  your current and past medications or 
therapies;  your physical examination results including height and weight, 
blood pressure readings, heart rate, breathing rate and temperature;  your 
laboratory test results including blood, urine, and pregnancy tests;  results 
of procedures, such as eye exams, tumor measurements or assessments, 
medical scans including CT, ECHO, and ECG scans;  tumor biopsy;  
results of genetic and biomarker testing;  and medical reports, such as the 
discharge summary and radiology, post-operative, and pathology reports.  
The researchers will also get information from your medical record 
(including hospital records from the Stanford Healthcare and your 
referring physician’s records).  
Who May Use or Disclose the Information?  
The following parties are authorized to use and/or disclose your health 
information in connection with this research study:  
• The Protocol Director, Jennifer Caswell-Jin, MD  
• Research Staff 
• The Stanford University Administrative Panel on Human Subjects in 
Medical Research  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 30 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your health 
information to the following persons and organizations for their use in 
connection with this research study:  
• QED Therapeutics, or their representatives  
• Helsinn Group, or their representatives 
• The Stanford Data and Safety Monitoring Committee (DSMC);  
and/or any other unit of Stanford University as necessary 
• The Food and Drug Administration (FDA) and/or other state or 
international regulatory authorities  
• The Office for Human Research Protections (OHRP) in the 
US Department of Health and Human Services (DHHS) 
• The US National Institutes of Health (NIH), including the National 
Cancer Institute (NCI)   
Your information may be re-disclosed by the recipients described above, if 
they are not required by law to protect the privacy of the information.  
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health information 
will end on 31 December 2099 or when the research project ends, 
whichever is earlier.   
 
Will access to my medical record be limited during the study? 
To maintain the integrity of this research study, you may not have access to 
any health information developed as part of this study until it is completed.  
At that point, you would have access to such health information if it was 
used to make a medical or billing decision about you (eg, if included in your 
official medical record).  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 31 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
___________________________________________ 
Printed Name of Adult Participant  
 
___________________________________________ 
____________  
Signature of Adult Participant  
 
 Date 
___________________________________________ 
 
If needed:   Printed Name of legally-authorized representative (LAR) 
___________________________________________ 
____________  
Signature of LAR  
 
Date 
___________________________________________ 
LAR’s Authority to Act for Participant  
(eg, parent, guardian, or conservator) 
 
NOTE:  If using the Short Form Consent process for informed consent in 
another language pursuant to an "Alteration of HIPAA Authorization," neither 
the participant nor their LAR should sign the HIPAA “Authorization To Use 
Your Health Information For Research Purposes” above.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 32 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
FINANCIAL CONSIDERATIONS 
Costs 
If you participate in this study, the study will pay for those services, supplies, procedures, 
and care associated with this study that are not a part of your routine medical care.  
However, there may be additional costs to you.  These include basic expenses like 
transportation and the personal time it will take to come to the Study Visits.   
You and/or your health insurance must pay for services, supplies, procedures, and care 
that are required during this study for routine medical care.  You will also be 
responsible for any co-payments and/or deductibles as required by your 
insurance.  If the costs of a co-payment related to the study are not covered by your 
insurer, managed care plan or other benefits program, you may be responsible for these 
costs.  If you are unable to pay for such costs, the Protocol Director and/or the Study 
Team will assist you in applying for supplemental benefits.  The study may cover any 
remaining excessive costs incurred for care or special medications required to continue 
participation in the study.  Participation in this study is not a substitute for health 
insurance.   
Some insurance companies or other 3rd-party payers may not pay for standard-of-care 
procedures or laboratory tests, including hospitalization, when they are done as part of a 
research study.  You should consult with your health benefit plan to determine whether 
your medical costs associated with your care during this study are covered.  
Payments / Reimbursement 
You may be reimbursed for reasonable travel expenses associated with the study visits.  
Please ask the study team for more details.  
Payments or reimbursement may only be made to US citizens, legal resident aliens, and 
those who have a work-eligible visa.  You may need to provide your Social Security 
Number (SSN) to receive payment.  If your SSN is required to receive payment, and you 
do not wish to provide your SSN, you have the option of declining the payment.  
This study includes the collection of research specimens.  Any of your specimens which 
are used in research, including those used in genetic research, may result in new 
products;  tests;  or discoveries.  In some instances, these products may have 
commercial value, and may be developed and owned by the study team;  
Stanford University;  QED Therapeutics and partner Helsinn Group (and their affiliates 
and collaborators) and/or others.  However, donors of specimens do not retain any 
property rights to the specimens or data derived from them.  Therefore, you would not 
share in any financial benefits from these products, tests or discoveries.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 33 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Any of your specimens which are used in research may result in new products, tests or 
discoveries.  In some instances, these may have potential commercial value and may be 
developed and owned by the study team;  Stanford University and/or others.  However, 
donors of specimens do not retain any property rights to the materials.  Therefore, you 
would not share in any financial benefits from these products, tests or discoveries.  
Funding Source  
QED Therapeutics and partner Helsinn Group are helping to pay for (sponsoring) this 
study, and providing the study drug Infigratinib and/or other materials for this study.  
The National Institutes of Health (NIH) / National Cancer Institute (NCI) is providing 
financial support and/or material for this study.  
Consultative or Financial Relationships   
None 
COMPENSATION for Research-Related Injury 
All forms of medical diagnosis and treatment – whether routine or experimental – 
involve some risk of injury.  In spite of all precautions, you might develop 
medical complications from participating in this study.  If such complications arise, the 
Protocol Director and the research study team will assist you in obtaining appropriate 
medical treatment.  In the event that you have an injury or illness that is directly caused 
by your participation in this study, care will be provided to you.  You will not be 
responsible for any of these costs.  
If you receive Medicare benefits, and if the sponsor of this study pays for any 
study-related treatment, complications or injuries, personal information about you, your 
treatment, and your participation in this study will be provided to the sponsor, who is 
required by law to provide it to Medicare.  
You do not waive any liability rights for personal injury by signing this form. 
CONTACT INFORMATION  
Questions, Concerns, Complaints, or to Report an Injury or Side Effect:  If you 
have any questions, concerns or complaints about this research study, its procedures, 
risks and benefits, or alternative courses of treatment, you should contact the 
Study Doctors Jennifer Caswell-Jin, MD at 650-724-3250, or a study team member.  
You should also contact them at any time if you feel you have been hurt by being a part 
of this study.  
If you are unable to reach anyone at the number(s) listed above, and you feel you may 
need medical attention, call or go to the nearest emergency room.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 34 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
Independent Contact:  If you are not satisfied with how this study is being conducted, 
or if you have any concerns, complaints, or general questions about the research or 
your rights as a participant, please contact the Stanford Institutional Review Board (IRB) 
to speak to someone independent of the research team at 650-723-5244 or toll-free at 
1-866-680-2906.  You can also write to the Stanford IRB, Stanford University, 
1705 El Camino Real, Palo Alto, CA 94306. 
Appointment or Alternate Contact:  If you need to change your appointment, or if you 
cannot reach the Study Doctor, please contact Study Team at 650-736-5790. 


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 35 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
As a research participant you have the following rights.  These rights include but are 
not limited to the participant's right to:  
• 
Be informed of the nature and purpose of the experiment;  
• 
Be given an explanation of the procedures to be followed in the 
medical experiment, and any drug or device to be utilized;  
• 
Be given a description of any attendant discomforts and risks reasonably 
expected;  
• 
Be given an explanation of any benefits to the subject reasonably to be expected, 
if applicable;  
• 
Be given a disclosure of any appropriate alternatives, drugs or devices that might 
be advantageous to the subject, their relative risks and benefits;  
• 
Be informed of the avenues of medical treatment, if any available to the subject 
after the experiment if complications should arise;  
• 
Be given an opportunity to ask questions concerning the experiment or the 
procedures involved;  
• 
Be instructed that consent to participate in the medical experiment may be 
withdrawn at any time and the subject may discontinue participation without 
prejudice;  
• 
Be given a copy of the signed and dated consent form; and  
• 
Be given the opportunity to decide to consent or not to consent to a medical 
experiment without the intervention of any element of force, fraud, deceit, duress, 
coercion or undue influence on the subject's decision.  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 36 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
May we contact you about future studies that may be of interest to you?  ___Yes ___No  
Signing your name means you agree to be in this study and that you will receive a copy 
of this signed and dated consent form.  
 
_______________________________________________ 
Printed Name of Adult Participant 
 
  
_______________________________________________ 
____________  
Signature of Adult Participant 
 Date 
 
_______________________________________________ 
If needed: Printed Name of Legally Authorized Representative (LAR) 
  
 
_______________________________________________ 
____________  
Signature of LAR 
 Date 
 
_______________________________________________ 
LAR’s Authority to Act for Participant (eg, parent, guardian, or conservator) 
 
_______________________________________________ 
Printed Name of Person Obtaining Consent (POC) 
 
 
_______________________________________________ 
____________  
Signature of POC 
 Date  


 
 
STANFORD UNIVERSITY   Research Consent Form 
Protocol Director: Jennifer L Caswell-Jin, MD 
Protocol Title:  A Phase 1B Study of Infigratinib in Combination with Tamoxifen in Hormone Receptor-Positive, 
HER2-Negative FGFR-Altered Advanced Breast Cancer 
 
 
 
Page 37 of 37 
 
Caswell-Jin IRB-53650 Cohort 1 ICF  3 December 2021  
NCT Number: NCT04504331 
Participant ID: 
IRB Use Only 
Approval Date:   May 11, 2022 
Expiration Date: May 11, 2023 
 
The following witness line is to be signed only if the consent is provided as a summary form and accompanied by a 
short-form foreign language informed consent document. 
_______________________________________________ 
Printed name of witness 
_______________________________________________ 
____________  
Signature of witness 
 Date 
 
(eg, staff, translator/interpreter, family member)  
The translated short form must be signed and dated by BOTH the participant (or their LAR) AND the witness.  
The English consent form (“referred to as the "Summary Form" in the regulations”):  
• 
Must be signed by BOTH the witness AND the Person Obtaining Consent (POC).  
• 
The non-English speaking participant / LAR does NOT sign the English consent.  
• 
The non-English speaking participant / LAR should NOT sign the HIPAA participant line.  
• 
If the participant / LAR is non-English speaking, the POC must ensure that:  
1) The LAR's Description of Authority is completed, and  
2)  Any questions or options presented by the consent form are documented and initialed by the  
     POC on the Summary Form, per the participant's wishes, as they are understood during the  
     consent process. .