A Phase 1/2a, Dose-escalation Study of FF-10502-01 for the Treatment of Advanced Solid Tumors and Lymphomas
Phase: PHASE1
Conditions: Solid Tumors, Lymphomas
Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Protocol No. FF1050201US101 
  
FUJIFILM Pharmaceuticals U.S.A., Inc. 
 
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CLINICAL STUDY PROTOCOL 
Protocol Number 
FF1050201US101 
Protocol Title 
A Phase 1/2a, dose-escalation study of FF-10502-01 for the treatment 
of advanced solid tumors 
Clinical Operations 
Contact 
Ruth Ann Subach, PharmD, BCPS 
Head, Clinical Operations and Project Management 
FUJIFILM Pharmaceuticals U.S.A., Inc. 
Phone: (484) 478-3754 
Email: rsubach@dsinpharmatics.com 
Sponsor / Medical 
Monitor 
David Wages, MD, PhD 
FUJIFILM Pharmaceuticals U.S.A., Inc. 
One Broadway 
Cambridge, MA 02142 
Phone: (508) 740-7500 
Email: david@docwages.com 
Original Protocol 
November 12, 2014 
Amendment #1  
October 22, 2015 
Amendment #2 
March 13, 2017 
Amendment #3 
July 14, 2017 
Amendment #4 
March 19, 2018 
Amendment #5 
December 06, 2018 
Amendment #6 
August 1, 2019 
 

Protocol No. FF1050201US101 
  
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INVESTIGATOR SIGNATURE PAGE 
I have reviewed the above-titled protocol and agree that it contains all the information necessary 
to conduct the study as required. I will conduct the trial in accordance with the principles of 
International Council for Harmonisation (ICH) Good Clinical Practice, the Declaration of Helsinki 
and the applicable U.S. Food and Drug Administration (FDA) regulations. 
I will maintain as confidential all written and verbal information provided to me by the Sponsor, 
including but not limited to, the protocol, case report forms, investigator’s brochure, material 
supplied at investigator meetings, minutes of teleconferences, etc. Such material will only be 
provided as necessary to site personnel involved in the conduct of the trial, the Institutional 
Review Board (IRB) or local regulatory authorities. 
I will obtain written informed consent from each prospective trial patient or each prospective trial 
patient’s legal representative prior to conducting any protocol-specified procedures. The 
Informed Consent Document (ICD) used will have the approval of the IRB. 
I will maintain adequate source documents and record all observations, treatments and 
procedures pertinent to trial patients in their medical records. I will accurately complete and 
submit the electronic case report forms supplied by the Sponsor in a timely manner. I will ensure 
that my facilities and records will be available for inspection by representatives of FUJIFILM 
Pharmaceuticals U.S.A., Inc. (FPHU), Westat, the IRB or local regulatory authorities. I will 
ensure that I and my staff are available to meet with representatives of FPHU and Westat during 
regularly scheduled monitoring visits. 
I will notify the Medical Monitor within 24 hours of any serious adverse events. Following this 
notification, a written report describing the serious adverse event will be provided to 
FPHU/Westat as soon as possible, but no later than 5 days following the initial notification. 
 
Principal Investigator’s Signature 
 
 
Date 
Principal Investigator’s Name (Print) 
 
 

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2 
SYNOPSIS 
Sponsor: 
FUJIFILM Pharmaceuticals U.S.A., Inc. 
Protocol Number: 
FF1050201US101 
Name of Study Drug: 
FF-10502-01 
Protocol Title: 
A Phase 1/2a Dose-escalation Study of FF-
10502-01 for the Treatment of Advanced 
Solid Tumors 
Name of Active Ingredient: 
4’-thio-FAC methane sulfonate 
Phase of Development: 
Phase 1/2a 
Primary Objective: 
• 
To determine the safety profile, maximum tolerated dose (MTD), dose-limiting 
toxicities (DLT) and recommended Phase 2 dose (RP2D) in patients who receive 
FF-10502-01 for treatment of advanced solid tumors 
Secondary Objectives: 
• 
To determine overall response rates 
• 
To determine the duration of response and duration of stable disease (SD) 
• 
To evaluate progression-free survival (PFS) 
• 
To evaluate overall survival (OS) 
• 
To evaluate the pharmacokinetics (PK) of FF-10502 
• 
To evaluate FF-10502 incorporation into whole blood cellular DNA as a 
pharmacodynamic marker 
Methodology: 
This is a Phase 1/2a, dose-escalation study of FF-10502-01. A total of up to N=161 patients 
with advanced solid tumors will be included. 
Major selection criteria are: age ≥ 18 years, histologically confirmed solid tumor or lymphoma 
(lymphoma in Phase 1 only), with documented disease progression following previous 
therapy. Patients must be ≥ 4 weeks beyond chemotherapy (or ≥ 5 half-lives for targeted 
agents, whichever is shorter), radiotherapy, major surgery, or other experimental treatments, 
and recovered from all acute toxicities (≤ Grade 1), have adequate renal and hepatic function, 
and no known history of significant cardiac disease. 
Phase 1:  
Following Screening, a total of up to 9 cohorts each will receive FF-10502-01 intravenously 
(IV) in 500 mL normal saline over a 1-hour period at doses of 8, 12, 18, 27, 40, 60, 90, 135 or 
200 mg/m2 weekly (Day 1, 8, 15) for three weeks, repeated every 28 days (= 1 cycle) until 
progression of disease. 
DLT will be defined as the following drug-related events: Grade 4 thrombocytopenia of any 
duration; other Grade 4 hematologic toxicity lasting ≥ 7 days; ≥ Grade 3 non-hematologic 
toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is adequately controlled with 
supportive care and resolves to ≤ Grade 2 within 48 hours); failure of Grade 3 platelets, 
absolute neutrophil count (ANC), or hemoglobin (Hb) to recover to Grade ≤ 1 within 4 weeks 
despite use of platelet and red blood cell (RBC) transfusions and/or growth factors; febrile 
neutropenia (defined as ANC < 1000/mm3 with a single temperature of > 38.3°C or sustained 
temperature of ≥ 38°C for over one hour); Grade 3 or 4 thrombocytopenia of any duration 

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associated with bleeding; or other toxicity-related treatment interruption that does not resolve 
to ≤ Grade 1 by Day 28 when the toxicity has received appropriate medical treatment. 
A single-patient dose escalation schema will be followed until the observation of ≥ Grade 2 
toxicity. One patient per cohort will be dosed and followed for 28 days through Cycle 1 for 
DLT. If no ≥ Grade 2 toxicity is seen, the next patient will be enrolled at the next dose level. 
Dose escalation will proceed in this manner until Grade 2 or greater toxicity is observed in at 
least one patient per cohort during the first 28 days. At that point, the current dose cohort will 
be expanded to 3 patients before proceeding in standard 3+3 manner. The dose escalation in 
subsequent cohorts will proceed in standard 3+3 manner. For all patient cohorts, if 1 of 3 
patients per cohort experiences DLT, the cohort will be expanded to 6. If 2 or more of 6 
patients per cohort experience DLT, all further dose escalation will stop. If the next lowest 
dose has only 3 patients, 3 more patients will be treated at that dose to verify it as the MTD. If 
that dose turns out to be too toxic, then this process will be repeated until the MTD is found 
through dose de-escalation. If 0 of 3 or ≤ 1 of 6 patients per cohort experience DLT by Day 28 
following dosing of FF-10502-01, dose escalation will proceed to the next cohort. The highest 
dose level below the dose level eliciting DLT in ≥ 2 patients will be declared the MTD. A total 
of 6 patients will be treated at the MTD. The MTD will be declared the RP2D. No intra-patient 
dose escalation will be allowed from previous dose levels until at least one patient has 
completed Cycle 1 at the higher dose level, with no Grade 2 or greater toxicities observed. 
Dose level adjustments for DLT will be made. Patients who experience DLT at the first dose 
level, 8 mg/m2, will not be dose-reduced, and will be discontinued. 
During the study, a Safety Review Committee (SRC) consisting of the actively recruiting 
investigators, the Medical Monitor, and FPHU, will review data from each cohort on an 
ongoing basis. Intermediate dose levels may be added if DLT is observed and it is 
recommended to do so by the SRC. Up to 54 patients are planned for Phase 1. 
Phase 2a:  
Once 6 patients are treated at the MTD in Phase 1, an additional 4 cohorts will be enrolled. 
Cohort 10 will enroll any patient with an advanced solid tumor who is otherwise eligible for 
this study (up to 20 patients). Cohort 11 will enroll patients with cholangiocarcinoma (up to 50 
patients). Cohort 12 will enroll patients with carcinoma of the gallbladder (up to 10 patients). 
Cohort 13 will enroll patients with urothelial carcinoma (up to 27 patients). Eligible patients 
enrolled in Phase 1 at the MTD may count towards the Phase 2a accrual. 
Both phases:  
The SRC will review patient data at least quarterly and make recommendations to FPHU 
regarding the conduct of the trial. Details of the SRC will be outlined in a separate SRC 
Charter. 
Patients in Cohorts 1 to 12 will receive FF-10502-01 on a weekly schedule for 3 weeks (Days 
1, 8, and 15), repeated every 28 days. The Phase 2a dose regimen is FF-10502-01 
90 mg/m2, administered on Days 1, 8, and 15 of a 28-day cycle. 
Patients in Cohort 13 (urothelial carcinoma) will receive 90 mg/m2 FF-10502-01 on a weekly 
schedule for 2 weeks (Days 1 and 8), repeated every 21 days.  
For all cohorts, blood samples for safety laboratory, PK, and pharmacodynamic assessments 
will be collected throughout the study. 
Disease assessments, based on computed tomography (CT) and/or magnetic resonance 
image (MRI), will be obtained at Week 8 and every 8 weeks thereafter until documented 

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progression of disease (PD) for Cohorts 1 to 12; and at Week 6 and every 6 weeks thereafter 
until documented PD for Cohort 13. Patients who demonstrate clinical benefit will be allowed 
to continue therapy with FF-10502-01 until progression of disease, observation of 
unacceptable adverse events, intercurrent illness or changes in the patient’s condition that 
prevents further study participation. 
Solid tumors will be assessed according to the Response Evaluation Criteria in Solid Tumors 
(RECIST v. 1.1)1. 
Number of Patients and Centers: 
Phase 1: Up to 54 patients are planned for the dose-escalation phase, with 6 of these 
patients treated at the MTD. 
Phase 2a: Four additional cohorts are planned; Cohort 10 (advanced solid tumors) will enroll 
up to 20 patients, Cohort 11 (cholangiocarcinoma) will enroll up to 50 patients, Cohort 12 
(gallbladder carcinoma) will enroll up to 10 patients, and Cohort 13 (urothelial carcinoma) will 
enroll up to 27 patients for a total of up to 107 patients. 
Entire study: Total N of up to 161 patients. 
The study will be conducted at The University of Texas M.D. Anderson Cancer Center, Filip 
Janku, M.D., Principal Investigator (PI) and Sarah Cannon Research Institute, Denver, CO, 
Gerald Falchook, M.D., PI. Drs. Janku and Falchook will serve as Co-PIs for the study. Once 
experience is gained at these institutions. Up to six additional sites may be added to complete 
study enrollment in a timely manner. 
Duration of Study:  
Accrual for the Phase 1 dose escalation phase was approximately 24 months. Accrual for the 
Phase 2a expansion phase is expected to be approximately 21 months, with the last patient 
followed up every 3 months until death or patient’s refusal to participate. The total study 
duration is expected to be approximately 57 months, through the last patient’s last follow-up. 
The anticipated Phase 2a accrual rate is 3 – 5 patients per month for Cohort 10 and 1-2 
patients per month for patients with cholangiocarcinoma, gallbladder carcinoma and urothelial 
carcinoma (Cohorts 11, 12 and 13). 
Inclusion Criteria: 
• 
Males and females ≥ 18 years of age 
• 
Patients must meet one of the following criteria: 
o Cohorts 1 to 10: Histologically or cytologically confirmed advanced or metastatic 
solid tumor or lymphoma (lymphoma in Phase 1 only), that is refractory to 
standard therapy, relapsed after standard therapy, or for which no standard 
therapy available that is expected to improve survival by at least three months 
(Cohort 10 in Phase 2a) 
Or  
Cohort 11 (Phase 2a): Histologically or cytologically confirmed intra- or extra-
hepatic cholangiocarcinoma that is refractory to standard therapy, relapsed after 
standard therapy, or for which no standard therapy available that is expected to 
improve survival by at least three months  
Or 

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o Cohort 12 (Phase 2a): Histologically or cytologically confirmed metastatic and/or 
unresectable gallbladder carcinoma that has progressed on gemcitabine-based 
therapy or another systemic therapy and for whom a clinical trial is an appropriate 
option. 
Or 
o Cohort 13 (Phase 2a): Histologically or cytologically confirmed metastatic and/or 
unresectable urothelial carcinoma that has progressed despite platinum-based 
therapy. (Note: evidence of progression within 12 months of peri-operative 
platinum-based therapy will be considered to have met progression criteria.) 
Patients must also have received a PD-1 or PD-L1 inhibitor and progressed or be 
ineligible for PD-1/PD-L1 inhibitor therapy or have refused such therapy. 
• 
At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, 
whichever is shorter), radiotherapy, major surgery or experimental treatment and 
recovered from all acute toxicities (≤ Grade 1) 
• 
Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 
(See APPENDIX A) 
• 
Life expectancy of ≥ 3 months 
• 
Adequate hematologic parameters without ongoing transfusional support: 
o Hemoglobin (Hb) ≥ 9 g/dL 
o Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L 
o Platelets ≥ 100 x 109 cells/L 
• 
Prothrombin time and activated partial thromboplastin time < 1.5 × the upper limit of 
normal (ULN) for the institution. Exceptions are permitted following approval by the 
Medical Monitor 
• 
Adequate renal and hepatic function: 
o Creatinine ≤ 1.5 x the ULN, or calculated creatinine clearance ≥ 60 mL/minute x 
1.73 m2 per the Cockcroft-Gault formula. Patients enrolled in Cohort 13 (urothelial 
cancer) must have a calculated creatinine clearance of >30 mL/minute x 1.73 m2 
per the Cockcroft-Gault formula. 
o Total bilirubin ≤ 2 times the ULN unless due to Gilbert’s disease 
o ALT and AST ≤ 2.5 times ULN, or < 5 times ULN for patients with liver metastases 
• 
QT interval corrected for rate (QTc) ≤ 480 msec on the electrocardiogram (ECG) 
obtained at Screening 
• 
Negative serum pregnancy test within 14 days prior to the first dose of study therapy 
for women of child-bearing potential (WCBP), defined as a sexually mature woman 
who has not undergone a hysterectomy or who has not been naturally post-
menopausal for at least 12 consecutive months (ie, who has had menses any time in 
the preceding 12 consecutive months). Sexually active WCBP and male patients must 
agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable 
hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with 
spermicide; or vasectomized partner) throughout the study and for 28 days after the 

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completion of study treatment. 
• 
Ability to provide written informed consent 
Exclusion Criteria: 
• 
Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, 
myocardial infarction, unstable angina or heart disease defined by the New York Heart 
Association (NYHA) Class III or Class IV (See APPENDIX B) 
• 
Active central nervous system (CNS) malignant disease in patients with a history of 
CNS malignancy. Patients with stable, previously or currently treated brain metastases 
are allowed. 
• 
Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface 
antigen (HBsAg), or positive hepatitis C antibody. Patients with positive HBsAg, low 
Hep B DNA, and normal LFTs and patients with low hepatitis C RNA may be 
considered for enrollment following discussion with the medical monitor. 
• 
Active infection requiring IV antibiotic usage within the last week prior to study 
treatment 
• 
Any other medical intervention or other condition which, in the opinion of the Principal 
Investigator, could compromise adherence to study requirements or confound the 
interpretation of study results 
• 
Pregnant or breast-feeding 
Criteria for evaluation: 
Safety: Safety will be assessed through the monitoring of AEs, clinical laboratory parameters 
(hematology, serum chemistry, urinalysis), vital sign measurements, and physical 
examinations. Adverse events will be classified according to the Medical Dictionary for 
Regulatory Affairs (MedDRA) and graded according to the National Cancer Institute Common 
Terminology Adverse Event (NCI CTCAE) version 4.03. 
Efficacy: Efficacy assessments will be determined on the basis of CT and/or MRI scans with 
best treatment response at any protocol-specified time point classified for solid tumors 
(RECIST v.1.1), and survival data (PFS and OS). 
Pharmacokinetics: Mean plasma concentrations of FF-10502 will be determined at each time 
point by dose cohort for evaluation of dose-linearity. Because a limited number of plasma 
concentrations will be determined, full determination of routine PK parameters may not be 
possible. In addition to mean plasma concentrations, as the data allow, additional PK 
analyses will be provided (trough levels, t1/2, Tmax, Cmax, AUC, etc) In Phase 2a, population PK 
methods will be utilized to characterize the PK profile of FF-10502. 
Pharmacodynamics: FF-10502 incorporation into whole blood cellular DNA will be correlated 
with clinical outcome. In Phase 2a expansion, PK data along with the pharmacodynamic data 
will be correlated with clinical outcome. 
Investigational product: 
FF-10502-01 is a pyrimidine nucleoside metabolic inhibitor anti-cancer drug to be 
administered by IV injection. FF-10502-01 exhibits cell cycle phase-specific activity, and 
primarily kills cells undergoing DNA synthesis (S-phase), thus blocking the progression of 
cells through the G1/S-phase boundary. 

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FF-10502-01 should be stored under refrigerated conditions at 2 – 8°C. 
The FF-10502-01 20 mg/mL drug product is manufactured by University of Iowa 
Pharmaceuticals (Iowa City, IA, USA) and will be provided by the Sponsor, FPHU. 
Reference therapy: None 
Statistical methods: 
Safety Endpoint Analyses: 
Safety endpoints for AEs include the following: incidences of all treatment-emergent adverse 
events (TEAEs) and all serious adverse events (SAEs); number and incidence of TEAEs and 
SAEs by severity; number and incidence of TEAEs and SAEs by relationship to study drug; 
number and incidence of all Grade 3 and 4 TEAEs and by severity and relationship to study 
drug; and discontinuation of patients from the study due to AEs or death. Safety endpoints for 
AEs, clinical laboratory tests, vital signs, ECG, and physical examination findings will be 
specified in the statistical analysis plan. Physical examination findings and ECGs will be 
listed. All other safety data will be summarized using descriptive statistics. 
Efficacy Endpoint Analyses: 
Response rates will be summarized using number and percentage of patients with a best 
response of CR, PR, SD or PD assessed by RECIST v 1.1 across all time points. For duration 
of response, duration of stable disease, PFS and OS, the Kaplan-Meier product- limit method 
will be used to estimate the median survival. Patients who do not have disease progression 
will be censored at the time of last contact. 
Progression-free survival will be calculated from the date of first treatment to the date of 
progression or death. 
Overall survival will be calculated from the date of first treatment to the date of death from any 
cause; patients who do not experience death will be censored at the time of last contact. 
SAS Version 9.4 or higher for Windows (SAS Institute, Cary, NC) or higher will be used for all 
analyses. 
Pharmacokinetic and Pharmacodynamic Endpoint Analyses: Analysis plans will be described 
in the written plans provided by the laboratories performing the analyses. 
 

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CONTENTS 
2 
SYNOPSIS ......................................................................................................................... 3 
3 
LIST OF ABBREVIATIONS ................................................................................................14 
4 
INTRODUCTION ...............................................................................................................17 
4.1 
FF-10502-01 Background ...........................................................................................17 
Figure 1. Chemical Structure of FF-10502-01 .....................................................................18 
4.2 
ZK 820973 Preclinical Summary .................................................................................18 
4.2.1 
ZK 820973 Preclinical Pharmacokinetics, Distribution, Metabolism, Excretion .....18 
4.2.2 
ZK 820973 Preclinical Safety Pharmacology........................................................19 
4.2.3 
ZK 820973 Genetic Toxicology ............................................................................19 
4.3 
FF-10502-01 Preclinical Studies .................................................................................19 
4.3.1 
FF-10502-01 In Vitro Anti-tumor Activity ..............................................................19 
Table 1. 
Growth Inhibition of FF-10502-01 and Gemcitabine in Human Tumor Cell Lines .20 
4.3.2 
FF-10502-01 In Vivo Anti-tumor Activity ...............................................................20 
Figure 2. Survival in SUIT-2 Orthotopic Pancreatic Xenograft Model Following Treatment 
with FF-10502-01 or Gemcitabine .........................................................................................21 
Figure 3. Tumor Growth Suppression and Body Weight in Capan-1 Subcutaneous 
Xenograft Model Following Treatment with FF-10502-01 or Gemcitabine ..............................22 
4.3.3 
FF-10502-01 Inhibition of DNA Synthesis ............................................................22 
4.3.4 
Preclinical Pharmacokinetics, Protein Binding, Liver Microsome Stability ............22 
4.4 
FF-10502-01 Toxicology .............................................................................................24 
4.4.1 
Dose Range-Finding and Repeat-Dose Toxicity Studies in Rats ..........................24 
4.4.2 
Dose Range-Finding and Repeat-Dose Toxicity Studies in Dogs .........................26 
4.5 
Dose Rationale ...........................................................................................................29 
5 
STUDY OBJECTIVES........................................................................................................31 
5.1 
Primary Objective:.......................................................................................................31 
5.2 
Secondary Objectives: ................................................................................................31 
6 
INVESTIGATIONAL PLAN .................................................................................................32 
6.1 
Overall Study Design ..................................................................................................32 
6.2 
Number of Patients and Centers .................................................................................34 
6.3 
Duration of Study ........................................................................................................34 
6.4 
Criteria for Termination of the Study ...........................................................................34 
7 
STUDY POPULATION .......................................................................................................36 
7.1 
Inclusion Criteria .........................................................................................................36 
7.2 
Exclusion Criteria ........................................................................................................37 

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7.3 
Discontinuation of Patients ..........................................................................................37 
7.3.1 
Procedures for Withdrawal ...................................................................................37 
7.3.2 
Replacement of Study Patients ............................................................................38 
8 
STUDY TREATMENT ........................................................................................................39 
8.1 
FF-10502-01 Investigational Product Description ........................................................39 
8.2 
Study Drug Administration ..........................................................................................39 
8.3 
Treatment Duration .....................................................................................................39 
8.4 
Dosing Delays, Dose Modifications Due to Toxicity, and Study Stopping Criteria .......39 
8.4.1 
Toxicity Grading Criteria ......................................................................................39 
8.4.2 
Instructions Regarding Dose Delays and Dose Modifications ..............................39 
8.4.3 
Study Stopping Criteria ........................................................................................40 
8.5 
Supportive Care Guidelines ........................................................................................40 
8.6 
Prior and Concomitant Medications and Therapies .....................................................40 
8.6.1 
Permitted Medications .........................................................................................40 
8.6.2 
Prohibited Therapy ..............................................................................................40 
8.7 
Packaging and Labeling ..............................................................................................40 
8.8 
Shipping and Storage .................................................................................................41 
8.9 
Drug Accountability .....................................................................................................41 
9 
STUDY PROCEDURES .....................................................................................................42 
9.1 
Screening Procedures ................................................................................................42 
9.2 
Treatment Cycles ........................................................................................................43 
9.2.1 
Requirements During Treatment Cycle 1 .............................................................43 
9.2.2 
Requirements During Treatment Cycles After Cycle 1 (Cycles 2, 3, 4, etc) ..........44 
9.3 
At Relapse or Progression of Disease.........................................................................45 
9.4 
End of Treatment (28 days, ± 5 days, from the last dose of Study Drug) .....................45 
9.5 
Long-term Follow-up ...................................................................................................46 
10 
DESCRIPTION OF ASSESSMENTS .............................................................................47 
10.1 Safety Assessments ...................................................................................................47 
10.1.1 
Adverse Event Definition ......................................................................................47 
10.1.2 
Serious Adverse Event ........................................................................................47 
10.1.3 
Unexpected Adverse Event ..................................................................................48 
10.1.4 
Adverse Event Reporting Period ..........................................................................48 
10.1.5 
Recording of Adverse Events ...............................................................................48 
10.1.6 
Adverse Event Reporting .....................................................................................49 

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Table 2. Reporting Guidelines for Adverse Events ................................................................50 
10.1.7 
Adverse Event and Serious Adverse Event Follow-Up .........................................50 
10.1.8 
Ongoing Safety Evaluation...................................................................................51 
10.1.9 
Clinical Laboratory Tests .....................................................................................51 
Table 3. Clinical Laboratory Parameters ................................................................................52 
10.1.10 Vital Sign Measurements .....................................................................................52 
10.1.11 Physical Examinations .........................................................................................52 
10.1.12 Electrocardiograms ..............................................................................................52 
10.1.13 Tumor Biopsy .......................................................................................................52 
10.2 Efficacy Assessments .................................................................................................53 
10.2.1 
Criteria for Evaluation of Response and Progression ...........................................53 
10.2.2 
Disease Response Criteria ..................................................................................53 
Table 4. Criteria for Overall Response for Target (+/- Non-target) Disease ............................53 
Table 5. Criteria for Overall Response for Non-target Disease Only ......................................54 
10.2.3 
Efficacy Endpoints ...............................................................................................54 
10.2.4 
Timing of Assessments to Determine Response ..................................................55 
10.2.5 
Pharmacokinetic Endpoints ..................................................................................55 
10.2.6 
Pharmacodynamic Endpoints ..............................................................................55 
11 
STATISTICAL METHODOLOGY ....................................................................................56 
11.1 Determination of Sample Size .....................................................................................56 
11.2 Analysis Populations ...................................................................................................57 
11.3 Statistical Analysis Methods ........................................................................................57 
11.3.1 
Safety Analyses ...................................................................................................57 
11.3.2 
Efficacy Analyses .................................................................................................58 
11.3.3 
Pharmacokinetic Endpoint Analysis .....................................................................58 
11.3.4 
Pharmacodynamic Endpoint Analysis ..................................................................58 
11.3.5 
Other Summaries .................................................................................................59 
12 
STUDY MANAGEMENT .................................................................................................60 
12.1 Data Management ......................................................................................................60 
12.2 Monitoring ...................................................................................................................60 
12.3 Audits and Inspections ................................................................................................60 
12.4 Amendments ...............................................................................................................60 
12.5 Record Keeping ..........................................................................................................60 
12.5.1 
Health Insurance Portability Accountability Act of 1996 ........................................60 

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12.5.2 
Financial Disclosure .............................................................................................61 
12.5.3 
Access to Original Records ..................................................................................61 
12.5.4 
Retention of Study Documents ............................................................................61 
13 
ADMINISTRATIVE STRUCTURE OF THE STUDY ........................................................62 
14 
REFERENCES ...............................................................................................................63 
15 
APPENDICES ................................................................................................................64 
APPENDIX A. Eastern Cooperative Group (ECOG) Performance Status Scale ....................65 
APPENDIX B. New York Heart Association (NYCA) Classification for Heart Failure ..............66 
APPENDIX C. FF-10502-01 Dosing Delays and Dose Modifications .....................................67 
APPENDIX D. Schedule of Study Procedures .......................................................................68 
Table 6: Schedule of Procedures for Cohorts 1-12 ................................................................69 
Table 7: Schedule of Procedures for Cohorts 13 ...................................................................71 
APPENDIX E. Ethical Standards ...........................................................................................73 
APPENDIX F. Investigator Obligations ..................................................................................75 
 
List of Tables 
Table 1. 
Growth Inhibition of FF-10502-01 and Gemcitabine in Human Tumor Cell Lines .....20 
Table 2. Reporting Guidelines for Adverse Events ....................................................................50 
Table 3. Clinical Laboratory Parameters ...................................................................................52 
Table 4. Criteria for Overall Response for Target (+/- Non-target) Disease ...............................53 
Table 5. Criteria for Overall Response for Non-target Disease Only ..........................................54 
Table 6: Schedule of Procedures for Cohorts 1-12 ....................................................................69 
Table 7: Schedule of Procedures for Cohorts 13 .......................................................................71 
List of Figures 
Figure 1. Chemical Structure of FF-10502-01 .........................................................................18 
Figure 2. Survival in SUIT-2 Orthotopic Pancreatic Xenograft Model Following Treatment with 
FF-10502-01 or Gemcitabine ....................................................................................................21 
Figure 3. Tumor Growth Suppression and Body Weight in Capan-1 Subcutaneous Xenograft 
Model Following Treatment with FF-10502-01 or Gemcitabine .................................................22 
List of Appendices 
APPENDIX A. Eastern Cooperative Group (ECOG) Performance Status Scale ........................65 
APPENDIX B. New York Heart Association (NYCA) Classification for Heart Failure .................66 
APPENDIX C. FF-10502-01 Dosing Delays and Dose Modifications ........................................67 

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APPENDIX D. Schedule of Study Procedures ..........................................................................68 
APPENDIX E. Ethical Standards ...............................................................................................73 
APPENDIX F. Investigator Obligations ......................................................................................75 

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3 
LIST OF ABBREVIATIONS 
Abbreviation  
Definition  
AE  
Adverse event  
ALT (SGPT)  
Alanine transaminase  
ANC  
Absolute neutrophil count  
APTT  
Activated partial thromboplastin time  
AST (SGOT)  
Aspartate transaminase  
AUC  
Area under the curve  
BM  
Bone marrow  
BUN  
Blood urea nitrogen  
C  
Celsius  
CFR  
Code of Federal Regulations  
CL  
Clearance  
cm  
Centimeter  
Cmax  
Peak concentration  
CNS  
Central nervous system  
CR  
Complete response, complete remission  
CRF  
Case report form  
CT  
Computed tomography  
CTCAE  
Common terminology criteria for adverse events  
CYP  
Cytochrome P450  
dL  
Deciliter  
DLT  
Dose limiting toxicity  
DNA  
Deoxyribonucleic acid  
ECG  
Electrocardiogram  
ECOG  
Eastern Cooperative Oncology Group  
EDTA  
Ethylenediaminetetraacetic acid  
ERC 
Ethic Review Committee 
FAC  
Arabinofuroanosyl cytosine  
FAS  
Full analysis set  
FDA  
Food and Drug Administration  
FDG  
Fluorodeoxyglucose  
FPHU  
FUJIFILM Pharmaceuticals, U.S.A., Inc.  
g  
Gram  
GALT 
Gut-associated lymphoid tissue 

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Abbreviation  
Definition  
GCP  
Good Clinical Practice  
G-CSF  
Granulocyte colony-stimulating factor  
GLP  
Good Laboratory Practice  
GM-CSF  
Granulocyte-macrophage colony-stimulating factor  
G1/S  
Gap 1/S phase interface  
Hb  
Hemoglobin  
HBsAg  
Hepatitis B surface antigen  
HCG  
Human chorionic gonadotropin  
HIPAA  
Health Insurance Portability and Accountability Act  
HIV  
Human immunodeficiency virus  
IC50  
Concentration producing 50% inhibition 
ICD  
Informed consent document  
ICH  
International Council for Harmonisation  
IND 
Investigational New Drug Application 
INR  
International normalized ratio (of prothrombin time) 
IWG  
International Working Group  
IRB  
Institutional Review Board  
IV  
Intravenous  
kg  
Kilogram  
L  
Liter  
LDH  
Lactate dehydrogenase  
M  
Molar  
m2 
Meters squared  
MCL  
Mantle cell lymphoma  
MedDRA  
Medical Dictionary for Regulatory Activities  
μ  
Micro  
mg  
Milligram  
mL  
Milliliter  
min  
Minute  
MRI  
Magnetic resonance imaging  
MTD  
Maximum tolerated dose  
n  
Nano  
NCI  
National Cancer Institute  
NYHA  
New York Heart Association  

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Abbreviation  
Definition  
OR  
Objective response  
OS  
Overall survival  
p  
Probability  
PBS  
Phosphate buffered saline  
PD  
Progression of disease  
PET  
Positron emission tomography  
PFS  
Progression-free survival  
PI  
Principal Investigator  
PK  
Pharmacokinetic  
PML 
Progressive multifocal leukoencephalopathy 
PR  
Partial response, partial remission  
PT  
Prothrombin time  
QTc  
QT interval corrected for rate  
RBC  
Red blood cell  
RECIST  
Response Evaluation Criteria in Solid Tumors  
RP2D  
Recommended Phase 2 dose  
SAE  
Serious adverse event  
SAS 
Statistical Analysis System 
SD  
Stable disease  
SRC  
Safety Review Committee  
T1/2  
Half-life  
TEAE  
Treatment-emergent adverse event  
Tmax  
Time to peak concentration  
ULN  
Upper limit of normal  
WCBP  
Woman of child-bearing potential 
 

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4 
INTRODUCTION 
4.1 
FF-10502-01 Background 
FF-10502, 4-amino-1-[(2R,3S,4S,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl) tetrahydrothiophen-
2-yl]pyrimidin-2(1H)-one, or 4’-thio-FAC, is a pyrimidine nucleoside antimetabolite anticancer 
agent. Pyrimidine antimetabolites exert cell cycle phase-specific activity by killing cells 
undergoing DNA synthesis (S-phase) and blocking the progression of cells through the 
G1/S-phase boundary. 
4’-thio-FAC was originally synthesized by Yamasa Corporation (Chiba, Japan) and licensed to 
Schering AG (Berlin, Germany) for development. The synthetic process was improved by 
Schering (reference code name ZK 820973). FUJIFILM acquired the compound in 2011, 
improved the synthetic process further, including solubility, and is now developing the 
methanesulfonate salt as FF-10502-01. The chemical structure of FF-10502-01 is depicted in 
Figure 1. 

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Figure 1. 
Chemical Structure of FF-10502-01 
 
ZK 820973 is the compound designation for studies previously conducted with FF-10502 (free 
base) by Schering AG. FF-10502-01 (methanesulfonate salt) is the test article used in all 
studies conducted under the direction of FUJIFILM. 
4.2 
ZK 820973 Preclinical Summary 
4.2.1 ZK 820973 Preclinical Pharmacokinetics, Distribution, Metabolism, 
Excretion 
Schering conducted nonclinical pharmacokinetic (PK), distribution, metabolism and excretion 
studies with ZK 820973. Following intravenous (IV) administration, these studies demonstrated 
that ZK 820973 has a similar profile to other pyrimidine nucleoside analogues, including 
gemcitabine.2,3  
The pharmacokinetics following single, bolus IV doses, 4 mg/kg in the mouse indicate a similar 
pharmacokinetic profile to gemcitabine. The half-life (t1/2) was 0.44 hours and area under the 
curve (AUC) was 1.4 μg*hr/mL, versus 0.14 hours and 0.7 μg*hr/mL for gemcitabine. 
In rats, single, bolus IV doses of 1, 5 or 20 mg/kg ZK 820973 or two doses of 2.5 mg/kg 
administered 1 hour apart, demonstrated dose-dependent systemic exposure in both sexes, 
however, 2 times administration of ZK 820973 show no difference in AUC, Cmax and other PK 
parameters compared to single administration of the same total dose. Different PK profiles were 
noted in females and males; higher Cmax, greater AUC and longer t1/2 noted in females versus 
males, resulting in overall lower exposure in males. 
In dogs, similar kinetics were noted between females and males following a single, bolus IV 
dose of 5 mg/kg; t1/2 was 16.6 hours, AUC was 21.5 μg*hr/mL, clearance (CL) was 
4.1 mL/min/kg; these values represent higher exposure in dogs relative to rats. 
ZK 820973 exhibited low protein binding following IV administration. 
Distribution of ZK 820973 in male and female rats following a single, bolus IV dose of 5 mg/kg 
14C-ZK 820973 indicated highest concentrations in the kidney. No long-lasting retention was 
noted in any organ or tissue. ZK 820973 passes through the blood-brain barrier, the placental 
barrier, and is expected to be secreted into milk. Elimination was mainly via the kidney. 
Metabolism was mainly by deamination in the mouse, dog, monkey and human, and less so in 
the rat. No metabolism of ZK 820973 was observed following incubation with human liver 
microsomes and isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, 
CYP2E1 and CYP3A4; therefore, there is no significant metabolism by the cytochrome P450 
enzyme system. Additionally, no interaction with CYP P450 enzymes was noted. Based on in 

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vitro inhibition studies, it was not expected that ZK 820973 would cause metabolic interactions 
when co-administered with drugs known to be cleared predominantly by CYP-dependent 
metabolism. Therefore, there is little potential for drug-drug interactions. 
4.2.2 ZK 820973 Preclinical Safety Pharmacology 
The cardiac effects of ZK 820973 were evaluated in vitro in guinea pig atria.3 Concentrations of 
ZK 820973 from 1 – 100 μmol/L were evaluated. The highest concentration (100 μmol/L) 
represented a ≥ 300-fold higher concentration than that needed to produce anti-proliferative, 
cytotoxic effects in MCL, pancreatic, ovarian, lung, colon, and prostate tumor cell lines. 
ZK 0820973 did not provoke significant effects on rate or force of contractions of isolated guinea 
pig atria in comparison to vehicle control. 
4.2.3 ZK 820973 Genetic Toxicology 
ZK 820973 was tested in the Ames Salmonella reverse mutation assay using strains TA98, 
TA100, TA1535, TA1537, and TA102.4 The compound was tested in both the presence and 
absence of S9 metabolic activation. ZK 820973 was found not to be mutagenic in the Ames 
strains tested either in the absence or presence of S9 metabolic activation. 
4.3 
FF-10502-01 Preclinical Studies 
4.3.1 FF-10502-01 In Vitro Anti-tumor Activity 
FF-10502-01 has demonstrated in vitro activity against pancreatic (BxPC-3, Capan-1, MIA 
PaCa-2, SUIT-2), colon (HCT116), lung (NCI-H460), ovarian (SK-OV-3), prostate (LNCaP.FGC) 
and mantle cell lymphoma (MCL) (Jeko-1) cell lines. The growth inhibition is shown in Table 1, 
as the mean of 3 experiments +/- SD. FF-10502-01 demonstrated growth inhibition activity with 
concentrations producing 50% inhibition (IC50s) of 30 – 330 nM; however the activity was 1.5- 
to15-fold lower than gemcitabine.5,6,7 

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Table 1. 
Growth Inhibition of FF-10502-01 and Gemcitabine in Human Tumor Cell Lines 
 
Abbreviations: IC50 = concentration producing 50% inhibition, MCL = mantle cell lymphoma 
4.3.2 FF-10502-01 In Vivo Anti-tumor Activity 
FF-10502-01 demonstrated in vivo activity in pancreatic xenograft models (SUIT-2, Capan-1) at 
doses achievable clinically. 
A human pancreatic cancer cell line (SUIT-2) was transplanted orthotopically into nude mice, 
and FF-10502-01 or gemcitabine was administered at 240 or 480 mg/kg once a week beginning 
on Day 7 after transplantation and continuing for 18 weeks.8 Each group consisted of N=20 
animals/group. The animals were followed up for 128 days after transplantation. Median survival 
in the vehicle control and 240 mg/kg gemcitabine groups was 55 and 110 days, respectively 
(p=0.0002). Median survival was not reached for the 480 mg/kg gemcitabine group or either the 
240 or 480 mg/kg FF-10502-01 groups. The survival rate was 5%, 25%, 75% for the vehicle, 
240 and 480 mg/kg gemcitabine groups (p<0.0001 versus vehicle), and 100% for the 240 and 
480 mg/kg FF-10502-01 groups (p<0.0001 versus gemcitabine groups), respectively (Figure 2). 

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Figure 2. 
Survival in SUIT-2 Orthotopic Pancreatic Xenograft Model Following Treatment with 
FF-10502-01 or Gemcitabine 
 
A cultured human pancreatic cancer cell line, Capan-1 was subcutaneously transplanted into 
the right flank of nude mice. Seven days after transplantation, FF-10502-01 or gemcitabine was 
administered at 120, 240 or 480 mg/kg once a week for 4 weeks.9 Tumor growth inhibitory 
effects of the test substance were evaluated for 27 days after starting treatment. Both 
FF-10502-01 and gemcitabine demonstrated statistically significant tumor growth suppression 
versus vehicle control; FF-10502-01 demonstrated tumor growth suppression with less effect on 
body weight than gemcitabine (Figure 3). Each graph represents 3 experiments ±SD. 

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Figure 3. 
Tumor Growth Suppression and Body Weight in Capan-1 Subcutaneous Xenograft 
Model Following Treatment with FF-10502-01 or Gemcitabine 
 
4.3.3 FF-10502-01 Inhibition of DNA Synthesis 
The effects of FF-10502-01 or gemcitabine on DNA synthesis in human pancreatic cancer-
derived cell lines (Capan-1) were evaluated for inhibition of DNA synthesis 50% (IC50).10 The 
mean IC50 (nmol/L) was 27.8 for FF-10502-01 and 29.6 for gemcitabine, indicating comparable 
inhibition of DNA synthesis in a human pancreatic cancer cell line. 
Additionally, FF-10502-01 demonstrated higher inhibitory potency than gemcitabine in an 
enzyme assay of DNA replication.11 The IC50s (μM) of DNA synthesis were 23 and 547 for 
FF-10502-01 and gemcitabine, respectively, demonstrating 23-fold higher inhibition than 
gemcitabine by DNA α-polymerase-mediated synthesis. 
4.3.4 Preclinical Pharmacokinetics, Protein Binding, Liver Microsome Stability 
4.3.4.1 
Pharmacokinetics 
Rat: The objective of the study was to determine the toxicokinetic profile when FF-10502-01 
was administered once weekly for three weeks (Days 1, 8 and 15) by intravenous infusion over 
a period of 1 hour to Sprague Dawley rats in a toxicology study conducted under Good 
Laboratory Practice (GLP) conditions described in Section 4.4.1.2 below.12  
The test and control/vehicle items were administered to groups of rats on 3 occasions (Days 1, 
8 and 15) by a 1-hour IV infusion at doses of 0, 100, 250 and 500 mg/kg (expressed as 
FF-10502 free base). Blood samples were collected from subsets of animals on Days 1 and 15 

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at 8 time points relative to treatment. A total of 3 animals per sex were evaluated for 
toxicokinetics from the control group; a total of 6 animals per sex were evaluated for 
toxicokinetics from the high dose group. 
FF-10502 was not detected in any of the samples collected from the Control animals on Days 1 
and 15. Similarly, FF-10502 was not detected in any of the pre-dose samples collected from the 
treated animals (100, 250 and 500 mg/kg dose groups) on Days 1 and 15. 
At doses of 100, 250 and 500 mg/kg/dose, exposure (based on Cmax and AUC0-Tlast /AUCINF 
values) to FF-10502 increased in a generally dose proportional manner for Cmax and AUC on 
both Day 1 and Day 15. Cmax was reached at 5 minutes post end of infusion for all animals. After 
reaching Tmax, the FF-10502 plasma concentrations declined rapidly at a mean estimated t1/2 
value ranging from 0.63 to 0.86 hours on Day 1 and from 0.75 to 0.90 hours on Day 15, at a 
dose of 100 mg/kg. On Day 15, the mean AUC0-Tlast was 211.5 and 200 hr*μg/mL for males and 
females, respectively, corresponding to a mean Cmax of 139.9 and 126.2 μg/mL, respectively, at 
a dose of 250 mg/kg. 
FF-10502 levels detected in all treated group samples collected at 12 hours post dose on 
Days 1 and 15 suggests that FF-10502-01 is eliminated within 12 hours of administration. There 
were no noteworthy sex-related differences in any of the measured toxicokinetic parameters. 
The once weekly IV infusion of FF-10502-01 over a period of 1 hour for 3 weeks did not result in 
any accumulation in rats. 
Dog: The objective of the study was to determine the toxicokinetic profile when FF-10502-01 
was administered once weekly for three weeks (Days 1, 8 and 15) by IV infusion over a period 
of 1 hour to Beagle dogs in a GLP toxicology study described in Section 4.4.2.2 below.13 Blood 
samples for toxicokinetic profiling were collected from the Main animals on Days 1 and 15 
(Day 8 for high-dose animals euthanized early) at a series of time points relative to treatment. A 
total of 1 animal per sex per group was evaluated for toxicokinetics at each respective dose 
level. 
FF-10502 was not detected in any of the samples collected from the control animals on Days 1 
and 15. Similarly, FF-10502 was not detected in any of the pre-dose samples collected from the 
treated animals on Days 1 and 8/15. 
At doses of 2.5, 5 and 10 mg/kg/dose (expressed as FF-10502 free base), exposure (based on 
Cmax and AUC0-Tlast/AUCINF values) increased in a generally dose proportional manner for Cmax 
and AUC on both Day 1 and Day 8/15, excepted for AUC in the high-dose males which 
increased in a slightly less than dose proportional manner on Day 8. Cmax was reached at 
5 minutes post end of infusion for all animals. After reaching Tmax, the FF-10502 plasma 
concentrations gradually declined at a mean estimated t1/2 value ranging from 2.78 to 3.95 hours 
on Day 1, and from 2.58 to 4.74 hours on Day 8/15. On Day 15, the AUC0-Tlast was 16.6 and 
13.8 hr*μg/mL for males and females, respectively, corresponding to a Cmax of 3.38 and 
2.85 μg/mL, respectively. 
FF-10502 levels noted in all of low-, mid- and high-dose samples collected at 24 hours post 
dose on Days 1 and 8/15 suggest that FF-10502-01 is eliminated within 24 hours of 
administration. There were no noteworthy sex-related differences in any of the measured 
toxicokinetic parameters. Once weekly IV infusion of FF-10502-01 over a period of 1 hour for up 
to 3 weeks did not result in an accumulation in dogs. 
4.3.4.2 
Protein Binding 
The plasma protein binding of FF-10502-01 was evaluated by means of equilibrium dialysis in 
plasma against phosphate buffered saline (PBS) at physiological conditions (37°C and pH 7.4), 

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at concentrations of 0, 0.137, 1.37, 4.13, 13.7, 41.3, 137 μM in rat, dog, and human plasma.14 
Time to reach equilibrium was determined to be 2 hours. FF-10502-01 was found to be stable in 
rat, dog and human plasma. Negligible plasma protein binding for FF-10502-01 was observed 
across all concentrations evaluated in rat, dog, and human plasma. The results of this study are 
consistent with the results obtained from the protein binding study previously conducted with 
ZK 820973. 
4.3.4.3 
Liver Microsome Stability 
The metabolic stability of FF-10502-01 was evaluated in human, rat, mouse and dog liver 
microsomes in order to predict in vivo metabolism, to determine the optimal species for 
assessment of the compound in in vivo animal studies.15 FF-10502-01 was found to be very 
stable metabolically in all tested species (mean t1/2 > 180 minutes), with intrinsic clearances of 9, 
6, 11 and 7 μL/min/mg in human, rat, mouse and dog liver microsomes, respectively. The 
observed differences in the metabolism rates were determined to be within experimental 
variability and did not indicate a difference between species with respect to FF-10502-01 
metabolism. 
4.4 
FF-10502-01 Toxicology 
4.4.1 Dose Range-Finding and Repeat-Dose Toxicity Studies in Rats 
4.4.1.1 
Dose Range-Finding in Rats 
This dose range-finding study was conducted in 2 parts. Phase 1 (dose-escalation) was 
conducted to determine the MTD of FF-10502-01 when administered once by intravenous 
infusion over a period of 1 hour to Sprague Dawley rats. Phase 2 (repeat-dose) was conducted 
to determine the toxicity of FF-10502-01 when administered weekly for 2 weeks (Days 1 and 8) 
by intravenous infusion over a period of 1 hour to Sprague Dawley rats.16  
Phase 1 (Dose-Escalation): This portion of the study was conducted to determine the MTD of 
FF-10502-01 when administered once by intravenous infusion over a period of 1 hour to 
Sprague Dawley rats. Doses of 0, 200, 400 and 100 mg/kg (FF-10502 free base) were 
administered to 2 animals per sex per group. An observation period of 4 days was allowed 
between successive dose levels. Parameters monitored included mortality, clinical observations, 
body weights, and food consumption; hematology, coagulation and clinical chemistry 
parameters were evaluated on Day 8. At termination, all animals were euthanized and subjected 
to a gross necropsy examination. Organ weights were measured on selected organs and a 
complete list of tissues, including gross lesions, were retained. 
Slight increases in platelets and reticulocyte counts were noted at doses up to 400 mg/kg. At 
1000 mg/kg, clinical signs, body weight loss (males only), decreases in food intake (male only), 
were noted, as well as increases in white blood cells and neutrophils in the animals of both 
sexes. The MTD was determined to be 400 mg/kg. 
Phase 2 (Repeat-Dose): This portion of the study was conducted to determine the toxicity profile 
when FF-10502-01 was administered weekly for 2 weeks (Days 1 and 8) by IV infusion over a 
period of 1 hour to Sprague Dawley rats (5 males and 5 females) at 750 mg/kg, an intermediate 
dose to the 400 and 1000 mg/kg doses evaluated above as single doses. Parameters monitored 
included mortality, clinical observations, body weights, and food consumption; hematology, 
coagulation, clinical chemistry and urinalysis parameters were evaluated on Day 15. At 
termination, all animals were euthanized and subjected to a gross necropsy examination. Organ 
weights were measured on selected organs and a complete list of tissues, including gross 
lesions, were retained and prepared for microscopic evaluation. 

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The weekly 1-hour intravenous infusion of FF-10502-01 for 2 weeks at a dose of 750 mg/kg 
resulted in mortality (two females), clinical signs, decreases in body weights and food 
consumption and increases in platelets, reticulocytes, white blood cells, neutrophils and 
monocytes. Macroscopically, test item related macroscopic observations in the spleen 
(enlargement), testes (small/soft and dark discoloration), thymus (small) and several lymph 
nodes (enlargement) were noted. Microscopically, test item related findings in the spleen 
(decreased cellularity in the white pulp and extramedullary hematopoiesis in the red pulp), 
testes (degeneration/atrophy) thymus (decreased cellularity) several lymph nodes (increased 
cellularity) and femoral bone marrow (enostosis) were noted. 
Therefore, the MTD in the dose range finding study in the rat was determined to be 400 mg/kg. 
4.4.1.2 
Repeat-Dose in Rats 
The objective of this GLP study was to determine the toxicity and toxicokinetic profile of 
FF-10502-01 when administered once weekly for three weeks (Days 1, 8 and 15) by IV infusion 
over a period of 1 hour to Sprague Dawley rats and to evaluate the persistence, delayed onset 
or reversibility of any test item-related effects following a 14-day recovery period.12 The 
toxicokinetic results are summarized in Section 4.3.4.1 above. 
The test and control/vehicle items were administered to groups of rats on 3 occasions (Days 1, 
8 and 15) by a 1-hour intravenous infusion at doses of 0, 100, 250 and 500 mg/kg (expressed 
as FF-10502 free base). A total of 10 animals per sex per group were included in the main 
study, and 5 animals per sex per group in the recovery study (control and high dose only). 
Parameters monitored during this study included mortality, clinical observations, body weights, 
food consumption and ophthalmology; hematology, coagulation, clinical chemistry and urinalysis 
parameters were evaluated on Day 22 (Main animals) and on Day 29 (Recovery animals). At 
termination (Day 22; Main animals; Day 29, Recovery animals), all animals were euthanized 
and subjected to a gross necropsy examination. Organ weights were measured on selected 
organs and a selected list of tissues, including gross lesions, were retained and prepared for 
microscopic evaluation. 
At a dose of 100 mg/kg/dose, IV infusion of FF-10502-01 resulted in no mortalities, no adverse 
clinical signs, no changes in body weights, food consumption, coagulation, serum chemistry or 
urinalysis parameters. In addition, there were no macroscopic or microscopic findings. 
Increases in reticulocyte count were noted, as was a decrease in lymphocyte count, testicular 
and thymic weights. 
At a dose of 250 mg/kg/dose, no mortalities were noted, nor were changes in coagulation or 
urinalysis parameters seen. Clinical signs, consisting mainly of inflammatory changes 
(suggestive of systemic septicemia) in the skin and subcutis (confirmed microscopically) and 
decreases in body weight gain (in males only) and food consumption were noted. Changes in 
hematology and clinical chemistry parameters were noted, as were decreases in testicular and 
thymic weights. Macroscopically, enlargement of the spleen and thickening of the skin and 
subcutis were noted. Microscopic changes included myeloid hypercellularity (with concurrent 
decrease in erythroid precursor cells) in the bone marrow (femur and sternum), decreased 
cellularity of thymus and spleen (white pulp), increased extramedullary hematopoiesis in spleen 
(red pulp), seminiferous tubular degeneration/atrophy (associated with oligospermia/aspermia) 
of the testes/epididymides. 
At a dose of 500 mg/kg/dose, no changes in coagulation or urinalysis parameters were noted. 
However, 1 male and 1 female rat were pre-terminally euthanized following the third dose due to 
poor condition. In these 2 pre-terminally euthanized animals, as well as in the animals surviving 
to termination, clinical signs were noted, consisting mainly of inflammatory changes (suggestive 

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of systemic septicemia) in the skin and subcutis (confirmed microscopically), hunched posture, 
decreased activity, thin body condition, reduced grooming activities (fur dull, ungroomed, 
matted), ptosis, dehydration and sensitivity to touch, and decreases in body weight gain and 
food consumption. Changes in hematology and clinical chemistry parameters were noted, as 
well as decreases in testicular and thymic weights and increases in splenic weight. Macroscopic 
observations were noted in the testes/epididymides (small and/or dark discoloration/soft), 
spleen (enlargement and/or pale area/material/adhesion), thymus (small), skin and subcutis 
(thickening/dark discoloration) and adrenals (dark/pale area). Microscopic changes included 
myeloid hypercellularity (with concurrent decrease in erythroid precursor cells) in the bone 
marrow (femur and sternum), decreased cellularity of thymus and spleen (white pulp), increased 
extramedullary hematopoiesis in spleen (red pulp), seminiferous tubular degeneration/atrophy 
(associated with oligospermia/aspermia) of the testes/epididymides. 
During the Recovery period (Day 22 to 29 following the last FF-10502-01 dose on Day 15), the 
majority of the clinical signs were reversible and were no longer seen beyond Day 22, except for 
reddening and swelling of the pinnae, which was still observed in all the Recovery females, and 
swelling of the left hind paw, in one male. Body weight gain and food consumption in high dose 
animals were comparable to controls; therefore, the effect on these parameters was considered 
reversible. In addition, changes in hematology and clinical chemistry parameters were noted, as 
well as decreases in testicular weight and increases in thymic and splenic weights. Macroscopic 
observations were still present in the testes/epididymides (small and/or soft), spleen 
(enlargement and raised area/adhesion) and skin and subcutis (thickening/dark discoloration). 
Microscopically, decreased cellularity (lymphoid depletion) in the thymus was no longer present, 
suggesting complete reversibility of the finding in the animals treated at 500 mg/kg/dose. Lower 
incidence and severity of myeloid hypercellularity was noted in the bone marrow, as was lower 
severity of decreased cellularity, and increased extramedullary hematopoiesis in the spleen, 
suggesting a partial to complete reversibility of the finding in the animals treated at 
500 mg/kg/dose. The testes/epididymides findings were still present in all the animals treated at 
500 mg/kg/dose. The testicular tubular degeneration/atrophy with oligospermia aspermia 
observed was not considered reversible. In addition, subcutaneous inflammation (skin and 
subcutis), suggestive of systemic septicemia, was still observed in one male and all of the 
female animals treated at 500 mg/kg/dose. 
Therefore, the MTD for FF-10502-01 when administered once weekly for 3 weeks in rats was 
determined to be 250 mg/kg. 
4.4.2 Dose Range-Finding and Repeat-Dose Toxicity Studies in Dogs 
4.4.2.1 
Dose Range-Finding in Dogs 
This dose range-finding study was conducted in 2 parts. Phase 1 (dose-escalation) was 
conducted to determine the MTD of FF-10502-01 when administered once by IV infusion over a 
period of 1 hour to Beagle dogs. Phase 2 (repeat-dose) was conducted to determine the toxicity 
of FF-10502-01 when administered weekly for 2 weeks (Days 1 and 8) by intravenous infusion 
over a period of 1 hour to Beagle dogs.17  
Phase 1 (Dose-Escalation): This portion of the study was conducted to determine the MTD of 
FF-10502-01 was administered once by IV infusion over a period of 1 hours to Beagle dogs. 
Doses of 0, 5, 10 and 25 mg/kg (FF-10502 free base) were administered to 1 animal per sex per 
group. An observation period of 4 days was allowed between successive dose levels. 
Parameters monitored during this study included mortality, clinical observations, body weights, 
and food consumption; hematology parameters were evaluated on Day 8. At termination, all 
animals were euthanized and subjected to a gross necropsy examination. Organ weights were 

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measured on selected organs and a complete list of tissues, including gross lesions, were 
retained. 
A dose of 5 mg/kg resulted in mild clinical signs (liquid/loose feces in 2 animals) as well as 
hematological changes consisting mainly of slight neutropenia. At a dose of 10 mg/kg, 
decreased food consumption was noted, as well as hematological changes, consisting mainly of 
moderate neutropenia and slight decreases in platelets, monocytes, eosinophils and basophils. 
A single dose of 25 mg/kg resulted in the following clinical signs: decreased activity, liquid feces, 
body weight loss, decreased food consumption and hematological changes consisting mainly of 
moderate neutropenia, slight lymphopenia and slight decreases in reticulocytes, platelets, 
monocytes, eosinophils and basophils. In the male, macroscopic changes were noted in the last 
infusion site, mesenteric and pancreatic lymph nodes. In the female, macroscopic changes were 
noted in the last infusion site, the digestive tract contents, colon, and pancreatic lymph node. 
The MTD was determined to be 10 mg/kg. 
Phase 2 (Repeat-Dose): The portion of the study was conducted to determine the toxicity profile 
when FF-10502-01 was administered weekly for 2 weeks (Days 1 and 8) by IV infusion over a 
period of 1 hour to Beagle dogs (2 males and 2 females) at 15 mg/kg, an intermediate dose to 
the 10 and 25 mg/kg doses evaluated above as single doses. All animals were to be observed 
for a period of 7 days following completion of dosing and then euthanized and subjected to a 
necropsy examination on Day 15. However, one female dog was found dead, while the 
remaining three were pre-terminally euthanized on Day 12 (4 days following the second dose), 
due to poor and deteriorating clinical condition. 
Parameters monitored during this study included mortality, clinical observations, body weights, 
and food consumption; hematology, coagulation, clinical chemistry and urinalysis parameters 
were evaluated on Days 8 and 12. At termination, all animals were euthanized and subjected to 
a gross necropsy examination. A complete list of tissues, including gross lesions, were retained 
and prepared for microscopic evaluation. 
The weekly IV infusion of FF-10502-01 for 2 weeks at a dose of 15 mg/kg resulted in severe 
clinical signs, marked body weight loss, severe decreases in food consumption, as well as 
changes to a number of hematology and clinical chemistry parameters and led to the death of 
one female and the pre-terminal euthanasia of the remaining 3 animals on Day 12 of the study. 
Microscopic changes observed in the found death and pre-terminally euthanized animals were 
similar and consisted mainly of decreased hematopoiesis of the femoral bone marrow, 
congestion and/or congestion/hemorrhage in the digestive tract (duodenum, jejunum, ileum 
colon, cecum and/or rectum), cryptal necrosis (duodenum, jejunum, colon, cecum and/or 
rectum), decreased cellularity of gut-associated lymphoid tissue (GALT), mandibular lymph 
node and/or thymus, congestion of the mandibular lymph node and/or mixed cell 
infiltrate/perivascular hemorrhage at the last infusion site. 
Therefore, the MTD in the dose range-finding study in the dog was determined to be 10 mg/kg. 
4.4.2.2 
Repeat-Dose in Dogs 
The objective of this GLP study was to determine the toxicity and toxicokinetic profile of 
FF-10502-01 when administered once weekly for 3 weeks (Days 1, 8 and 15) by IV infusion 
over a period of 1 hour to Beagle dogs and to evaluate the persistence, delayed onset or 
reversibility of any test-item related effects following a 14-day recovery period.13 The 
toxicokinetic results are summarized in Section 4.3.4.1 above. 
The objective of the study was to determine the toxicity and toxicokinetic profile of the test item, 
FF-10502-01, when administered once weekly for three weeks (Days 1, 8 and 15) by 

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intravenous infusion over a period of 1 hour to Beagle dogs and to evaluate the persistence, 
delayed onset or reversibility of any test item-related effects following a 14-day recovery period. 
The test and control/vehicle items were administered to groups of dogs on 3 occasions (Days 1, 
8 and 15) by a 1-hour IV infusion at doses of 0, 2.5, 5 and 10 mg/kg (expressed as FF-10502 
free base). A total of 3 animals per sex per group were included in the main study, and 2 
animals per sex per group in the recovery study (control and high dose only). 
Parameters monitored during this study included mortality, clinical observations, body weights, 
food consumption, ophthalmology, blood pressure and electrocardiograms; hematology, 
coagulation, clinical chemistry and urinalysis parameters were evaluated on Day 22. Following 
the third dose on Day 15, the Group control and low dose Main animals were observed for a 
period of 7-days and then euthanized and subjected to a necropsy examination on Day 22. The 
control group Recovery animals were to be observed for 14 days following completion of the last 
dose (Day 15) and then euthanized and subjected to a necropsy examination on Day 29, 
however, due to the pre-terminal euthanasia of all high-dose Recovery animals, the control 
group Recovery animals were euthanized and subjected to a necropsy examination on Day 22 
along with the Main animals. The mid- and high-dose Main animals were to be observed for a 
period of 7 days following their third dose (Day 15) and then euthanized and subjected to a 
necropsy examination on Day 22, while the high-dose Recovery animals were to be observed 
for 14 days following completion of the last dose (Day 15) and then euthanized and subjected to 
a necropsy examination on Day 29. However, due to the pre-terminal euthanasia of two high-
dose Recovery males on Days 8 and 9, respectively, following 1 or 2 doses, the high-dose Main 
animals and the remaining high-dose Recovery females were euthanized on Day 10 (2 days 
following administration of the second dose). The high-dose Main animals were reassigned as 
Recovery animals, dosed on Day 8 and were to be euthanized on Day 22 (2 weeks following 
administration of the second dose). However, in view of their poor clinical condition, all of the 
remaining high-dose animals were euthanized between Days 13 and 15 (after receiving 2 doses 
only), while all the animals from the mid-dose group were euthanized between Days 14 and 17 
(after receiving 2 to 3 doses). 
At a dose of 2.5 mg/kg/dose, FF-10502-01 resulted in no mortalities, no changes in 
ophthalmology, blood pressure, electrocardiography, coagulation or urinalysis parameters. In 
addition, there were no macroscopic or microscopic findings. Clinical signs were noted in a 
small number of animals, marginal body weight loss and decreases in food consumption, 
decreases in white blood cells (mainly neutrophils, lymphocytes and/or eosinophils), as well as 
decreases in thymic weights. The decreased in the weight of the thymus were minor and were 
not associated with any macroscopic or microscopic correlates. 
At a dose of 5 mg/kg/dose, no changes in ophthalmology, blood pressure, electrocardiography, 
coagulation or urinalysis parameters were noted, and no macroscopic findings were observed. 
Adverse clinical signs, body weight loss and decreased food consumption (males only) was 
noted, which led to the pre-terminal euthanasia of all animals between Days 14 and 17 following 
the administration of 2 to 3 doses of FF-10502-01. Changes in hematology and clinical 
chemistry parameters were noted and decreased thymic and testicular weights. Microscopic 
changes included decreased cellularity (lymphoid depletion) in the thymus and GALT, 
hypocellularity of the bone marrow (sternum and/or femur), atrophy of the testicular 
seminiferous tubular epithelium and pulmonary inflammation (suppurative/hemorrhagic 
bronchioloalveolar and/or granulomatous inflammation) mostly associated with a secondary 
bacterial infection. 
At a dose of 10 mg/kg/dose, no changes in ophthalmology, blood pressure, electrocardiography 
or urinalysis parameters were noted. Adverse clinical signs, body weight loss and decreased in 

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food consumption were observed, which led to the death or pre-terminal euthanasia of all 
animals between Days 8 and 15 of the study following the administration of 1 to 2 doses of 
FF-10502-01. Changes in hematology, coagulation and clinical chemistry parameters, were 
noted, as well as decreases in thymic and testicular weights. Macroscopic changes included 
mottling or dark area/discoloration of the lungs, presence of a mass in the ventricular chamber 
of the heart, raised area in the atrioventricular valve of the heart and small thymus. Microscopic 
changes included decreased cellularity (lymphoid depletion) in the thymus and GALT, 
hypocellularity of the bone marrow (sternum and/or femur), atrophy of the testicular 
seminiferous tubular epithelium, pulmonary inflammation (suppurative/hemorrhagic 
bronchioloalveolar and/or granulomatous inflammation) mostly associated with secondary 
bacterial infection and mural thrombosis or blood clot formation in the heart. 
The combined effects of immunosuppression and/or secondary bacterial sepsis were 
considered to be the major cause of the death or poor clinical condition that led to the premature 
euthanasia of the 5 and 10 mg/kg/dose animals and are not unexpected findings for cytotoxic 
agents given at high doses. 
Therefore, the MTD for FF-10502-01 when administered once weekly for 3 weeks in dogs was 
determined to be 2.5 mg/kg/dose. 
4.5 
Dose Rationale 
The toxicity of FF-10502-01 was evaluated in two repeat-dose GLP studies conducted in the rat 
and the dog, as described respectively in Sections 4.4.1.2 and 4.4.2.2 above. Both studies were 
conducted over a range of doses IV weekly x 3 weeks followed by a 2-week recovery period. 
Findings typical of a pyrimidine nucleoside analogue were determined, including 
lympho-hematopoietic organ hypocellularity (bone marrow, thymus and spleen) and decreased 
spermatogenesis (rat). Changes were generally reversible following the 14-day recovery period. 
The MTD was found to be 250 mg/kg (1500 mg/m2) in the rat and 2.5 mg/kg (50 mg/m2) in the 
dog. The dog was the more sensitive of the 2 species; therefore, the proposed starting dose in 
the human was 1/6 of the MTD in the dog, or 8 mg/m2. 
In the Phase 1 study of FF-10502-01, a single dose escalation schema was followed until 
observation of ≥ Grade 2 toxicity, which was observed in the first dose cohort. At that point, a 
standard 3+3, dose-escalation schema was followed. 
In the dose-escalation phase of the study, a cumulative total of 38 patients (19 male, 19 female) 
were enrolled on study in 9 dose cohorts over a dose range of 8-135 mg/m2. Preliminary data 
suggest that FF-10502-01 is well tolerated and demonstrates early signals of clinical activity. 
Partial responses have been demonstrated in two patients with cholangiocarcinoma, one at 
Cohort 5 (40 mg/m2) through 10 cycles, and one at Cohort 6 (60 mg/m2) through 4 cycles. Three 
additional patients with cholangiocarcinoma demonstrated stable disease over 2 to 8 cycles. 
Two additional partial responses have been demonstrated, one in a patient with chondroblastic 
osteogenic sarcoma (Cohort 3, 18 mg/m2) who achieved an unconfirmed partial response (73% 
decrease) in a maxillary mass, and one in a patient with bladder cancer at Cohort 8 (135 
mg/m2). Stable disease has been demonstrated in an additional six patients, one each with 
pancreatic, prostate, breast, and adenoid cystic carcinoma of the oropharynx, and two with 
parotid cancer. 
The principal toxicities appear to be gastrointestinal (GI), which can largely be mitigated by 
standard prophylactic anti-emetic medications. One event of Grade 3 nausea which met DLT 
definition was observed at 40 mg/m2 despite pre-medication. Grade 1/2 fever, chills, and rash 
are also commonly observed. Cytopenias have been infrequent, with Grade 1/2 
treatment-related anemia reported in only 5 patients, one Grade 3 event of neutropenia at 

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135 mg/m2, and no clinically significant thrombocytopenia. Five patients were dose reduced for 
AEs of mild dysgeusia, severe hypotension, life-threatening hypotension and moderate to 
severe fatigue, all possibly-related to study drug. Dose escalation was terminated at 135 mg/m2 
due to DLT of infusion-like reactions (pyrexia, chills, Grade 3/4 hypotension). Grade 3 fatigue 
and ≥ Grade 1 rash were observed at an intermediate dose level of 100 mg/m2 subsequently 
evaluated, and the RP2D for the Phase 2a expansion is 90 mg/m2. 
As PD-1/PD-L1 inhibitors are now being used for the treatment of urothelial cancers, in 
Cohort 13, the dose of 90 mg/m2 will be used but in a schedule that matches that of PD-1/PD-L1 
inhibitor therapy. Namely, FF-10502-01 will be administered IV on Days 1 and 8 of a 21-day 
cycle.  
In the Phase 2a expansion, 36 patients were enrolled at the time of writing this protocol 
amendment. One patient in the expansion phase developed progressive multifocal 
leukoencephalopathy (PML) during the course of the study. The patient received 7 cycles of 
FF10502-01 for cholangiocarcinoma and presented with classic signs of PML. As is common in 
human immunodeficiency virus (HIV)-negative PML patients, there were no remarkable 
changes in the patient’s lymphocyte count or in other laboratory parameters. Prior treatments 
included rituximab, approximately 2 years prior to the onset of PML. While prior rituximab 
exposure and chemotherapy may have triggered the development of PML, the contribution of 
FF10502-01 to the development of PML cannot be excluded. 

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5 
STUDY OBJECTIVES 
5.1 
Primary Objective: 
• 
To determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities 
(DLT) and recommended Phase 2 dose (RP2D) in patients who receive FF-10502-01 for 
advanced solid tumors 
5.2 
Secondary Objectives: 
• 
To determine the overall response rates 
• 
To determine the duration of response and duration of stable disease (SD) 
• 
To evaluate progression-free survival (PFS) 
• 
To evaluate overall survival (OS) 
• 
To evaluate the PK of FF-10502 
• 
To evaluate FF-10502 incorporation into whole blood cellular DNA as a 
pharmacodynamic marker 

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6 
INVESTIGATIONAL PLAN 
6.1 
Overall Study Design 
This is a Phase 1/2a, dose-escalation study of FF-10502-01. A total of up to N=161 patients 
with advanced solid tumors, including lymphomas (for Phase 1 only), will be included. 
Major selection criteria are: age ≥ 18 years, histologically confirmed solid tumor or lymphoma 
(lymphoma in Phase 1 only), with documented disease progression following previous therapy. 
Patients must be ≥ 4 weeks beyond chemotherapy (or ≥ 5 half-lives for targeted agents, 
whichever is shorter), radiotherapy, major surgery, or other experimental treatments, and 
recovered from all acute toxicities (≤ Grade 1), have adequate renal and hepatic function, and 
no known history of significant cardiac disease. 
Phase 1: 
Following Screening, a total of up to 9 cohorts each will receive FF-10502-01 intravenously (IV) 
in 500 mL normal saline over a 1-hour period at doses of 8, 12, 18, 27, 40, 60, 90, 135 or 
200 mg/m2 weekly (Day 1, 8, 15) for three weeks, repeated every 28 days (= 1 cycle) until 
progression of disease. 
Dose-limiting toxicity will be defined as the following drug-related events: Grade 4 
thrombocytopenia of any duration; other Grade 4 hematologic toxicity lasting ≥ 7 days; 
≥ Grade 3 non-hematologic toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is 
adequately controlled with supportive care and resolves to ≤ Grade 2 within 48 hours); failure of 
Grade 3 platelets, absolute neutrophil count (ANC), or hemoglobin (Hb) to recover to Grade ≤ 1 
within 4 weeks despite use of platelet and red blood cell (RBC) transfusions and/or growth 
factors; febrile neutropenia (defined as ANC < 1000/mm3 with a single temperature of > 38.3°C 
or sustained temperature of ≥ 38°C for over one hour); Grade 3 or 4 thrombocytopenia of any 
duration associated with bleeding; or other toxicity-related treatment interruption that does not 
resolve to ≤ Grade 1 by Day 28 when the toxicity has received appropriate medical treatment. 
A single-patient dose escalation schema will be followed until the observation of ≥ Grade 2 
toxicity. One patient per cohort will be dosed and followed for 28 days through Cycle 1 for DLT. 
If no ≥ Grade 2 toxicity is seen, the next patient will be enrolled at the next dose level. Dose 
escalation will proceed in this manner until Grade 2 or greater toxicity is observed in at least one 
patient per cohort during the first 28 days. At that point, the current dose cohort will be 
expanded to 3 patients before proceeding in standard 3+3 manner. The dose escalation in 
subsequent cohorts will proceed in standard 3+3 manner. For all patient cohorts, if 1 of 3 
patients per cohort experiences DLT, the cohort will be expanded to 6. If 2 or more of 6 patients 
per cohort experience DLT, all further dose escalation will stop. If the next lowest dose has only 
3 patients, 3 more patients will be treated at that dose to verify it as the MTD. If that dose turns 
out to be too toxic, then this process will be repeated until the MTD is found through dose de-
escalation. All patients will be followed for 28 days for DLT. If 0 of 3 or ≤ 1 of 6 patients per 
cohort experience DLT by Day 28 following dosing of FF-10502-01, dose escalation will proceed 
to the next cohort. The highest dose level below the dose level eliciting DLT in ≥ 2 patients will 
be declared the MTD. A total of 6 patients will be treated at the MTD. The MTD will be declared 
the RP2D. No intra-patient dose escalation will be allowed from previous dose levels until at 
least one patient has completed Cycle 1 at the higher dose level, with no Grade 2 or greater 
toxicities observed. 
Dose level adjustments for DLT will be made. Patients who experience DLT at the first dose 
level, 8 mg/m2, will not be dose-reduced, and will be discontinued. 

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During the study, a Safety Review Committee (SRC) consisting of the actively recruiting 
investigators, the Medical Monitor, and FPHU, will review data from each cohort on an ongoing 
basis. Intermediate dose levels may be added if DLT is observed and it is recommended to do 
so by the SRC. Up to 54 patients are planned for Phase 1. 
Phase 2a:  
Once 6 patients are treated at the MTD in Phase 1, an additional 4 cohorts will be enrolled. 
Cohort 10 will enroll any patient with an advanced solid tumor who is otherwise eligible for this 
study (up to 20 patients). Cohort 11 will enroll patients with cholangiocarcinoma (up to 50 
patients). Cohort 12 will enroll patients with carcinoma of the gallbladder (up to 10 patients). 
Cohort 13 will enroll patients with urothelial carcinoma (up to 27 patients). 
Eligible patients enrolled in Phase 1 at the MTD may count towards the Phase 2a accrual. 
Cohorts 1 to 12 (Both Phases): 
Patients in Cohorts 1 to 12 will receive FF-10502-01 on a weekly schedule for 3 weeks (Days 1, 
8, and 15), repeated every 28 days. The Phase 2a dose regimen is FF-10502-01 90 mg/m2, 
administered on Days 1, 8, and 15 of a 28-day cycle. 
Blood samples for PK assessment of FF-10502 plasma concentrations for patients in Cohorts 1 
to 12 will be collected on Cycle 1 Days 1 and 15 pre-dose, immediately following cessation of 
infusion (within 15 minutes), between 1-2 hours post-infusion, and between 4-6 hours post-
infusion. Incorporation of FF-10502 into cellular DNA of whole blood will be assessed as a 
pharmacodynamic endpoint pre-dose Cycle 1, Days 1, 8, and 15, and during the Day 22 visit. 
Blood for hematology and serum chemistry determinations will be collected within 28 days 
before Cycle 1 Day 1, on Days 1, 8, 15 and 22 of Cycle 1, on Day 1 of each subsequent cycle 
and at the End of Treatment Visit. After Cycle 1, blood for hematology also will be collected 
pre-dose on Days 8 and 15 of each cycle. Urine will be collected for urinalysis within 28 days 
before Cycle 1 Day 1, on Day 1 of each cycle and at the End of Treatment Visit. 
Cohort 13 (Phase 2a): 
Patients in Cohort 13 (urothelial carcinoma) will receive FF-10502-01 on a weekly schedule for 
2 weeks (Days 1 and 8), repeated every 21 days. 
Blood samples for PK assessment of FF-10502 plasma concentrations for patients in Cohort 13 
will be collected on Cycle 1 Days 1 and 8, pre-dose, immediately following cessation of infusion 
(within 15 minutes), between 1-2 hours post-infusion, and between 4-6 hours post-infusion. 
Incorporation of FF-10502 into the cellular DNA of whole blood will be assessed as a 
pharmacodynamic endpoint pre-dose on Cycle 1 Days 1 and 8; and at any time during the 
Cycle 1 Day 15 visit. Blood for hematology and serum chemistry determinations will be collected 
within 28 days before Cycle 1 Day 1, on Days 1, 8, and 15 of Cycle 1, on Day 1 of each 
subsequent cycle, and at End of Treatment. After Cycle 1, blood for hematology also will be 
collected pre-dose on Day 8 of each cycle. Urine will be collected for urinalysis within 28 days 
before Cycle 1 Day 1, on Day 1 of each cycle, and at the End-of-Treatment Visit. 
All Cohorts (Both Phases): 
Disease assessments, based on computed tomography (CT) and/or magnetic resonance image 
(MRI), will be obtained at Week 8 and every 8 weeks thereafter until documented progression of 
disease (PD) for Cohorts 1 to 12; and at Week 6 and every 6 weeks thereafter until documented 
PD for Cohort 13. Patients who demonstrate clinical benefit will be allowed to continue therapy 
with FF-10502-01 until progression of disease, observation of unacceptable adverse events, 
intercurrent illness or changes in the patient’s condition that prevents further study participation. 

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Safety will be assessed through the monitoring of AEs, clinical laboratory parameters 
(hematology, serum chemistry), vital sign measurements, and physical examinations. Adverse 
events will be classified according to the Medical Dictionary for Regulatory Affairs (MedDRA) 
and graded according to the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTCAE) version 4.03. 
Efficacy assessments for solid tumors will be made according to the Response Evaluation 
Criteria in Solid Tumors (RECIST v. 1.1)1
 P.  
Mean plasma concentrations of FF-10502 will be determined at each time point for evaluation of 
dose-linearity. Because a limited number of plasma concentrations will be determined, full 
determination of routine PK parameters may not be possible. In addition to mean plasma 
concentrations, as the data allow, additional PK analyses will be provided (trough levels, t1/2, 
Tmax, Cmax, AUC, etc). In Phase 2a, population PK methods will be utilized to characterize the PK 
profile of FF-10502. 
FF-10502 incorporation into the cellular DNA of whole blood will be determined as a 
pharmacodynamic endpoint. In Phase 2a expansion, PK data along with the pharmacodynamic 
data will be correlated with clinical outcome. 
The SRC will review patient data at least quarterly and make recommendations to FPHU 
regarding the conduct of the trial. Details of the SRC will be outlined in a separate SRC Charter. 
Study stopping criteria are defined in Section 8.4.3. 
6.2 
Number of Patients and Centers 
Phase 1: Up to 54 patients are planned for the dose-escalation phase, with 6 of these patients 
treated at the MTD. 
Phase 2a: Four additional cohorts are planned; Cohort 10 (advanced solid tumors) will enroll up 
to 20 patients, Cohort 11 (cholangiocarcinoma) will enroll up to 50 patients, Cohort 12 
(gallbladder carcinoma) will enroll up to 10 patients, and Cohort 13 (urothelial carcinoma) will 
enroll up to 27 patients for a total of up to 107 patients.  
Entire study: Total N of up to 161 patients. 
The study will be conducted at The University of Texas M.D. Anderson Cancer Center, Filip 
Janku, M.D., Principal Investigator (PI) and Sarah Cannon Research Institute, Denver, CO, 
Gerald Falchook, M.D., PI. Drs. Janku and Falchook will serve as Co-PIs for the study. Once 
experience is gained at these institutions. Up to six additional sites may be added to complete 
study enrollment in a timely manner. 
6.3 
Duration of Study 
Accrual for the Phase 1 dose escalation phase was approximately 24 months. Accrual for the 
Phase 2a expansion phase is expected to be up to 21 months, with the last patient followed up 
to 6 months. The total study duration is expected to be approximately 57 months, through the 
last patient’s last follow-up. The anticipated Phase 2a accrual rate is 3 – 5 patients per month 
for Cohort 10 and 1-2 patients per month for patients with cholangiocarcinoma, gallbladder 
cancer, or urothelial carcinoma (Cohorts 11, 12, and 13). 
6.4 
Criteria for Termination of the Study 
If the sponsor, investigator, study monitor, or officials from the Food and Drug Administration 
(FDA) discover conditions arising during the study that indicate that the study should be halted 

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or that the study site should be terminated, this action may be taken after appropriate 
consultation between the sponsor and investigator. 
Conditions that may warrant termination include, but are not limited to, the following: 
• 
The discovery of an unexpected, serious, or unacceptable risk to patients enrolled in the 
study 
• 
A decision on the part of the sponsor to suspend or discontinue testing, evaluation, or 
development of the product 
• 
Failure of an investigator to enroll patients into the study at an acceptable rate 
• 
Failure of an investigator to comply with pertinent FDA regulations 
• 
Submission of knowingly false information from the study site to the sponsor, study 
monitor, or the FDA 
• 
Insufficient adherence to protocol requirements 
Study termination and follow-up would be performed in compliance with the conditions set forth 
in 21 CFR 312.50 and 21 CFR 312.56. 

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7 
STUDY POPULATION 
7.1 
Inclusion Criteria 
Patients must meet all of the following criteria to participate in the study: 
• 
Males and females ≥ 18 years of age 
• 
Patients must meet one of the following criteria: 
o Cohorts 1 to 10: Histologically or cytologically confirmed advanced or metastatic 
solid tumor or lymphoma (lymphoma in Phase 1 only), that is refractory to standard 
therapy, relapsed after standard therapy, or for which no standard therapy available 
that is expected to improve survival by at least three months (Cohort 10 in Phase 2a) 
Or 
o Cohort 11 (Phase 2a): Histologically or cytologically confirmed intra- or extra-
hepatic cholangiocarcinoma that is refractory to standard therapy, relapsed after 
standard therapy, or for which no standard therapy available that is expected to 
improve survival by at least three months  
Or 
o Cohort 12 (Phase 2a): Histologically or cytologically confirmed metastatic and/or 
unresectable gallbladder carcinoma that has progressed on gemcitabine-based 
therapy or another systemic therapy and for whom a clinical trial is an appropriate 
option 
Or 
o Cohort 13 (Phase 2a): Histologically or cytologically confirmed metastatic and/or 
unresectable urothelial carcinoma that has progressed despite platinum-based 
therapy. (Note: evidence of progression within 12 months of peri-operative platinum-
based therapy will be considered to have met progression criteria.) Patients must 
also have received a PD-1 or PD-L1 inhibitor and progressed or be ineligible for 
PD-1/PD-L1 inhibitor therapy or have refused such therapy. 
• 
At least 4 weeks beyond the last chemotherapy (or ≥ 5 half-lives for targeted agents, 
whichever is shorter), radiotherapy, major surgery or experimental treatment and 
recovered from all acute toxicities (≤ Grade 1) 
• 
Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 (See 
APPENDIX A) 
• 
Life expectancy of ≥ 3 months 
• 
Adequate hematologic parameters without ongoing transfusional support: 
o Hemoglobin (Hb) ≥ 9 g/dL 
o Absolute neutrophil count (ANC) ≥ 1.0 x 109 cells/L 
o Platelets ≥ 100 x 109 cells/L 
• 
Prothrombin time and activated partial thromboplastin time < 1.5 × the ULN for the 
institution. Exceptions are permitted following approval by the Medical Monitor 
• 
Adequate renal and hepatic function: 

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o Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinine clearance 
≥ 60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula. Patients enrolled in 
Cohort 13 (urothelial cancer) must have a calculated creatinine clearance of 
>30 mL/minute x 1.73 m2 per the Cockcroft-Gault formula. 
o Total bilirubin ≤ 2 times the ULN unless due to Gilbert’s disease 
o ALT and AST ≤ 2.5 times ULN, or < 5 times ULN for patients with liver metastases 
• 
QT interval corrected for rate (QTc) ≤ 480 msec on the electrocardiogram (ECG) 
obtained at Screening 
• 
Negative serum pregnancy test within 14 days prior to the first dose of study therapy for 
women of child-bearing potential (WCBP), defined as a sexually mature woman who has 
not undergone a hysterectomy or who has not been naturally post-menopausal for at 
least 12 consecutive months (ie, who has had menses any time in the preceding 12 
consecutive months). Sexually active WCBP and male patients must agree to use 
adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal 
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; 
or vasectomized partner) throughout the study and for 28 days after the completion of 
study treatment. 
• 
Ability to provide written informed consent 
7.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from the study: 
• 
Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, 
myocardial infarction, unstable angina or heart disease defined by the New York Heart 
Association (NYHA) Class III or Class IV (See APPENDIX B) 
• 
Active central nervous system (CNS) malignant disease in patients with a history of CNS 
malignancy. Patients with stable, previously or currently treated brain metastases are 
allowed. 
• 
Known positive for HIV, hepatitis B virus surface antigen (HBsAg), or positive hepatitis C 
antibody. Patients with positive HBsAg, low Hep B DNA, and normal LFTs and patients 
with low hepatitis C RNA may be considered for enrollment following discussion with the 
medical monitor. 
• 
Active infection requiring IV antibiotic usage within the last week prior to study treatment 
• 
Any other medical intervention or other condition which, in the opinion of the PI, could 
compromise adherence to study requirements or confound the interpretation of study 
results 
• 
Pregnant or breast-feeding 
7.3 
Discontinuation of Patients 
7.3.1 Procedures for Withdrawal 
Any patient may be removed from study for the following reasons: 
• 
Patient withdrawal of consent 
• 
Patient noncompliance 

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• 
An increasing or unexpected pattern of unacceptable toxicity 
• 
Disease progression 
• 
Investigator judgment when the well-being and best interest of the patient is 
compromised 
Patients experiencing unacceptable toxicity should be removed from the study once complete 
resolution of toxicity has been documented. Individual patients may be discontinued from the 
study by the investigator or sponsor at any time if either determines that it is not in the best 
interest of the patient to continue. 
Any patient who becomes pregnant during the study must be discontinued from study treatment 
immediately but should be followed through delivery or termination of the pregnancy. Patients 
should also notify the investigator if they become pregnant within 28 days following the last dose 
of study drug. FPHU/Westat also must be notified if a patient becomes pregnant on study. 
If a patient is discontinued from the study before completing the specified duration of treatment, 
they should be encouraged to complete the end-of-study assessments and to agree to report 
any serious adverse events for 28 days following the last dose of study drug. The date the 
patient is withdrawn and the primary reason for discontinuation will be recorded on the case 
report form (CRF). 
7.3.2 Replacement of Study Patients 
Patients who are screened, but do not receive FF-10502-01, will be replaced. 

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8 
STUDY TREATMENT 
8.1 
FF-10502-01 Investigational Product Description 
FF-10502-01 is a pyrimidine nucleoside antimetabolite anticancer drug for IV administration. 
Nucleoside analogues exert cell cycle phase-specific activity by primarily killing cells undergoing 
DNA synthesis (S-phase), thus blocking the progression of cells through the G1/S-phase 
boundary. 
The FF-10502-01 20 mg/mL drug product is manufactured by University of Iowa 
Pharmaceuticals (Iowa City, IA, USA) and will be provided to clinical study sites directly from the 
drug distribution center designated by FPHU. 
8.2 
Study Drug Administration 
Patients should be scheduled to begin study therapy following completion of Screening.  
FF-10502-01 is compatible with both dextrose 5% in water (D5W) and 0.9% sodium chloride 
(normal saline; NS) when diluted to a final concentration between 50 µg/mL and 1.5 mg/mL. 
After admixture, the final IV admixture may be maintained at room temperature or under 
refrigeration (2-8°C) for up to 24 hours. The infusion will be administered over a 1-hour period. 
Phase 1: Patients will receive FF-10502-01 weekly IV at the dose level prescribed per cohort on 
Days 1, 8 and 15 of each 28-day cycle (= 1 cycle). 
Phase 2a, Cohorts 10 to 12: Patients will receive FF-10502-01 90 mg/m2 IV on Days 1, 8 and 15 
of each 28-day cycle (= 1 cycle). 
Phase 2a, Cohort 13: Patients will receive FF-10502-01 90 mg/m2 IV on Days 1 and 8 of each 
21-day cycle (= 1 cycle). 
8.3 
Treatment Duration 
Treatment will continue until confirmation of disease progression, unacceptable toxicity, or 
patient decision to discontinue therapy. 
8.4 
Dosing Delays, Dose Modifications Due to Toxicity, and Study Stopping 
Criteria 
8.4.1 Toxicity Grading Criteria 
Toxicity grading is based on NCI Common Terminology Criteria for Adverse Event v 4.03 
(http://evs.nci.nih.gov/ftp1/CTCAE/About.html). 
8.4.2 Instructions Regarding Dose Delays and Dose Modifications 
Adverse events considered for treatment interruption and dose reduction will exclude the events 
assessed by the investigator as exclusively related to underlying disease or medical 
condition/concomitant treatment. If treatment must be delayed for reasons other than toxicity, 
contact the Medical Monitor to discuss the reasons for delay and plans for resuming study 
therapy. 
• 
Treatment may be delayed up to 14 days. If the patient has completed two cycles and, in 
the investigator’s opinion, is receiving benefit, treatment may be delayed for longer than 
14 days and then resumed following a discussion with the Medical Monitor. Patients who 
require the next treatment cycle to be held for more than 14 days due to ongoing toxicity 
from the prior cycle should have the dose reduced by 25%. 

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• 
Patients who experience a toxicity requiring reduction in dose level may continue 
treatment at the lower dose level until disease progression or unacceptable toxicity. The 
dose level may be reduced twice. Patients who continue to require dose modifications 
beyond this should be discontinued from the trial. Once the dose has been reduced it 
may not be escalated. 
• 
See APPENDIX C for FF-10502-01 dose modification requirements. 
8.4.3 Study Stopping Criteria 
The occurrence of any new cases of PML will prompt FPHU to immediately halt any 
recruitment and consult with the FDA as the details of the new case are acquired. Details 
include confirmation of diagnosis per established criteria, history of past medication 
associated with PML and other items of interest. Treatment of other patients on study may 
be withdrawn upon consultation with the FDA and investigators. 
8.5 
Supportive Care Guidelines 
• 
Medications may be administered for the management of symptoms associated with the 
administration of FF-10502-01, as required. 
• 
Adequate treatment for nausea and/or vomiting and diarrhea is permitted at the 
discretion of the Investigator. 
• 
Infusion reactions were reported at the RP2D of 90 mg/m2; pre-treatment with 
corticosteroids or other medications may be given at the Investigator’s discretion. 
• 
Granulocyte stimulating growth factors (eg, G-CSF or GM-CSF) are not allowed during 
Cycle 1 except for the following situations: Grade 4 neutropenia lasting ≥ 7 days, failure 
of ≥ Grade 3 ANC to recover to Grade 1 within 4 weeks, or febrile neutropenia (defined 
as ANC < 1000/mm3 with a single temperature of > 38.3°C or sustained temperature of 
≥ 38°C for over one hour). After Cycle 1, use of granulocyte growth factors are allowed 
for prophylaxis or management of neutropenia. 
• 
Erythropoiesis-stimulating agents, transfusions, etc, are permitted for management of 
hematologic toxicities. 
8.6 
Prior and Concomitant Medications and Therapies 
8.6.1 Permitted Medications 
All medications and other treatments taken by patients 4 weeks before and throughout the study 
period will be recorded in the CRF module. Any changes in documented, permitted concomitant 
medications being taken at the beginning of the clinical trial or added during the time the patient 
is participating in this study must be recorded in the CRF module. 
8.6.2 Prohibited Therapy 
Concurrent anti-tumor therapy is prohibited other than chronic hormonal therapy (e.g., 
anastrozole or leuprolide). Any other investigational agent is prohibited. 
8.7 
Packaging and Labeling 
FF-10502-01 will be provided for IV administration in individual doses as a sterile solution as 
20 mL in a clear 30-mL capacity glass vial (20 mg/mL, calculated as free base). The study drug 

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vials will be labeled with product name, strength, Lot No. and other information as per local 
regulatory requirements. 
8.8 
Shipping and Storage 
 FF-10502-01 vials and FF-10502-01 prepared dosing solution should be stored under 
refrigerated conditions (2 – 8°C). 
8.9 
Drug Accountability 
The investigator must maintain accurate records of receipt of study drug, dispensing 
information, and the prompt return or destruction of unused supplies. A drug accountability log 
will be supplied to each clinical site for purposes of recording study drug dispensation for the 
study and will be monitored by sponsor personnel. If the site has an electronic study drug 
accountability form that is in keeping with institutional practice and the form collects the same 
information as the form supplied by the Sponsor, this form may be substituted for the Sponsor’s 
drug accountability form. 
Unused or expired FF-10502-01 will be destroyed per institutional policy. 

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9 
STUDY PROCEDURES 
See Schedule of Study Procedures in APPENDIX D. Unless otherwise specified, the study 
procedures listed in the following subsections apply to all cohorts. 
9.1 
Screening Procedures 
The following evaluation includes standard tests that are to be performed within 28 days prior to 
the first administration of study treatment to determine patient eligibility. 
• 
Administration of informed consent 
• 
Medical history, physical examination and vital signs 
o In addition to the medical history collected at Screening to determine eligibility, 
patients will be queried to determine whether they have a history of autoimmune 
disease or treatment associated with an elevated risk of PML. Specifically, 
patients will be queried about a history of: 
 
Systemic lupus erythematosus  
 
Rheumatoid arthritis  
 
Sjogren’s syndrome  
 
Dermatomyositis or polymyositis  
 
Idiopathic thrombocytopenic purpura  
 
Vasculitis (cryoglobulenic, Giant cell etc)  
 
Multiple sclerosis and treatment with an integrin inhibitor such as 
natalizumab  
 
Hematologic malignancy such as lymphoma and treatment with rituximab 
or anti-CD20 therapy 
Medical history pertaining to any autoimmune disease or treatment associated 
with an elevated risk of PML will be entered in the clinical database but does not 
constitute eligibility criteria.  
• 
ECOG Performance Status 
• 
Height and weight 
• 
The following lab tests: (See Table 3 for a list of lab tests) 
o Hematology 
o Coagulation parameters 
o Serum chemistry 
o Urinalysis 
• 
β-HCG for WCBP within 14 days prior to the first dose of FF-10502-01 
• 
12-lead ECG 
• 
Patients may consent to an optional tumor biopsy during screening. (Refer to 
Section 10.1.13) 
• 
Review of concomitant medications 
• 
Disease-specific assessment (CT, MRI scans) 

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9.2 
Treatment Cycles 
9.2.1 Requirements During Treatment Cycle 1 
9.2.1.1 
Cycle 1, Day 1 
• 
Abbreviated physical examination 
• 
Vital signs 
• 
ECOG Performance Status 
• 
Weight 
• 
The following lab tests: (See Table 3 for a list of lab tests) 
o Hematology, if not performed within the previous 72 hours. Note: In addition to total 
lymphocyte counts, T cell (CD4 and CD8) and B cell counts will be obtained. 
o Serum chemistry, if not performed within the previous 72 hours 
o Urinalysis, if not performed within the previous 72 hours 
• 
Patients who have not done so at screening may consent to an optional tumor biopsy 
during Cycle 1. (Refer to Section 10.1.13) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Administration of FF-10502-01 over a 1-hour period 
• 
Peripheral blood collection in EDTA for PK assessments, pre-dose, immediately 
following cessation of infusion (within 15 minutes), between 1-2 hours post-infusion, and 
between 4-6 hours post-infusion 
• 
Peripheral blood collection in sodium heparin for pharmacodynamic assessment, pre-
dose 
9.2.1.2 
 Cycle 1, Day 8 (±1 day) 
• 
Vital signs 
• 
The following lab tests: (See Table 3 for a list of lab tests) 
o Hematology 
o Serum chemistry 
• 
Patients who have not done so at screening may consent to an optional tumor biopsy 
during Cycle 1. (Refer to Section 10.1.13) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Administration of FF-10502-01 over a 1-hour period 
• 
Cohort 13 only: Peripheral blood collection in EDTA for PK assessments, pre-dose, 
immediately following cessation of infusion (within 15 minutes), between 1-2 hours 
post-infusion, and between 4-6 hours post-infusion 

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• 
Peripheral blood collection in sodium heparin for pharmacodynamic assessment, pre-
dose 
9.2.1.3 
Cycle 1, Day 15 (±1 day) 
• 
Vital signs 
• 
The following lab tests: (See Table 3 for a list of lab tests) 
o Hematology 
o Serum chemistry 
• 
Patients who have not done so at screening may consent to an optional tumor biopsy 
during Cycle 1. (Refer to Section 10.1.13) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Cohorts 1 to 12 only: Administration of FF-10502-01 over a 1-hour period 
• 
Cohorts 1 to 12 only: Peripheral blood collection in EDTA for PK assessments, pre-
dose, immediately following cessation of infusion (within 15 minutes), between 1-2 hours 
post-infusion, and between 4-6 hours post-infusion 
• 
Peripheral blood collection in sodium heparin for pharmacodynamic assessment, pre-
dose (Cohorts 1 to 12) or any time during visit (Cohort 13) 
9.2.1.4 
Cycle 1, Day 22 (±1 day) [Cohorts 1 to 12 only] 
• 
Vital signs 
• 
The following lab tests: (See Table 3 for a list of lab tests) 
o Hematology 
o Serum chemistry 
• 
Patients who have not done so at screening may consent to an optional tumor biopsy 
during Cycle 1. (Refer to Section 10.1.13) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Peripheral blood collection in sodium heparin for pharmacodynamic assessment during 
visit 
9.2.2 Requirements During Treatment Cycles After Cycle 1 (Cycles 2, 3, 4, etc) 
9.2.2.1 
Day 1 of Each Cycle (± 2 days) 
• 
Abbreviated physical examination 
• 
Vital signs 
• 
ECOG Performance Status 
• 
Weight 
• 
The following lab tests (within 3 days of each cycle – see Table 3 for a list of lab tests): 

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o Hematology. Note: In addition to total lymphocyte counts, T cell (CD4 and CD8) and 
B cell counts will be obtained.  
o Serum chemistry 
o Urinalysis 
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Administration of FF-10502-01 over a 1-hour period  
9.2.2.2 
Day 8 of Each Cycle (±2 days) 
• 
The following lab tests (see Table 3 for a list of lab tests): 
o Hematology  
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Administration of FF-10502-01 over a 1-hour period  
9.2.2.3 
Day 15 of Each Cycle (±2 days) [Cohorts 1 to 12 only] 
• 
The following lab tests (see Table 3 for a list of lab tests): 
o Hematology  
• 
Review of concomitant medications 
• 
Assessment of AEs 
• 
Administration of FF-10502-01 over a 1-hour period  
9.2.2.4 
End of Cycle 2 and Every 2 Cycles Thereafter (±3 days) 
• 
Disease-specific assessment (CT, MRI scans) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
9.3 
At Relapse or Progression of Disease 
• 
Disease-specific assessment (CT, MRI scans) 
• 
Review of concomitant medications 
• 
Assessment of AEs 
9.4 
End of Treatment (28 days, ± 5 days, from the last dose of Study Drug)  
• 
Physical examination 
• 
Vital signs 
• 
ECOG Performance Status 
• 
Weight 
• 
The following lab tests: (See Table 3 for a list of lab tests) 

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o Hematology. Note: In addition to total lymphocyte counts, T (CD4 and CD8) and B 
cell counts will be obtained at end of treatment. 
o Serum chemistry 
o Urinalysis 
• 
12-lead ECG 
• 
Review of concomitant medications 
• 
Assessment of AEs 
9.5 
Long-term Follow-up 
Long-term follow-up will consist of a clinic visit or telephone call every 3 months until death or 
patient’s refusal to participate to assess survival. 

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10 
DESCRIPTION OF ASSESSMENTS 
10.1 
Safety Assessments 
10.1.1 Adverse Event Definition 
An adverse event (AE) includes any noxious, pathological, or unintended change in anatomical, 
physiological, or metabolic functions as indicated by physical signs, symptoms, and/or 
laboratory changes occurring whether or not temporally associated with study drug 
administration and whether or not considered related to study drug. This definition includes an 
exacerbation of pre-existing medical conditions or events, intercurrent illnesses, hypersensitivity 
reactions, drug interactions, or clinically significant laboratory findings. 
An AE does not include the following: 
• 
Medical or surgical procedures, eg, tooth extraction, transfusion, surgery (The medical 
condition that leads to the procedure is to be recorded as an AE.) 
• 
Pre-existing conditions or procedures present or detected at the start of the study that do 
not worsen 
• 
Hospitalization for elective surgeries or for other situations in which an untoward medical 
event has not occurred 
• 
Abnormal laboratory value, unless it is clinically significant 
• 
Overdose of study drug or concomitant medication unaccompanied by signs/symptoms 
(If sign/symptoms occur, the final diagnosis should be recorded as an AE.) 
• 
Pregnancy by itself, unless a complication occurs during pregnancy leading to 
hospitalization; in this case (The medical condition that leads to the hospitalization is to 
be recorded as the AE.) 
• 
A significant worsening of the disease under investigation which is captured as an 
efficacy parameter in this study and, thus, is not to be recorded as an AE. 
10.1.2 Serious Adverse Event 
A serious adverse event (SAE) is defined as an adverse event that results in any of the 
following outcomes: 
• 
Death 
• 
Life-threatening, ie, immediate risk of death from the event as it occurred; (This does not 
include an adverse event that, had it occurred in a more serious form, might have 
caused death.) 
• 
Persistent or substantial disability/incapacitation 
• 
Results in or prolongs an existing inpatient hospitalization 
• 
Congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based on medical judgment, they may 
jeopardize the patient or may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. 

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10.1.3 Unexpected Adverse Event 
An AE or suspected adverse reaction is considered "unexpected" if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or severity that has been observed; or, is 
not consistent with the risk information described in the protocol or elsewhere. For example, 
under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the 
Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, 
cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater 
specificity) if the Investigator’s Brochure listed only cerebral vascular accidents. 
"Unexpected," as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the Investigator’s Brochure as occurring with a class of drugs or as anticipated 
from the pharmacological properties of the investigational therapy, but are not specifically 
mentioned as occurring with the investigational therapy. 
10.1.4 Adverse Event Reporting Period 
The adverse event reporting period begins from the date of the first dose of study drug to 
28 days following the last dose of study drug. 
10.1.5 Recording of Adverse Events 
Each AE should be recorded in standard medical terminology on the AE CRF module. 
Whenever possible, the AE should be evaluated and reported as a diagnosis rather than as 
individual signs or symptoms. For example, cough, runny nose, sneezing, sore throat, and head 
congestion should be reported as ‘upper respiratory infection’. If a definitive diagnosis is not 
possible, the individual signs and symptoms should be recorded. Dates of start (onset) and stop 
(recovery), action taken, and outcome will be recorded in the AE CRF module. 
All clinically significant abnormal changes in laboratory parameters will be recorded as an AE on 
the AE module, with the following exceptions: clinically significant abnormal laboratory changes 
determined to be related to the study condition and concomitant conditions, eg, diabetes, of 
which the investigator was previously aware and that have not worsened. 
The investigator will evaluate all AEs with regard to maximum intensity and relationship to study 
drug, as follows. 
10.1.5.1 Maximum Intensity 
Maximum intensity should be assigned using one of the severity grades as outlined in the 
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 
v4.03); if the AE is not specifically listed in CTCAE v4.03, use the following grades: 
• 
Grade 1: mild 
• 
Grade 2: moderate 
• 
Grade 3: severe 
• 
Grade 4: life-threatening 
• 
Grade 5: death 
10.1.5.2 Relationship to Study Drug 
The degree of certainty with which an AE is attributed to study drug (or alternative causes, eg, 
natural history of the underlying diseases, concomitant therapy, etc) will be determined by how 
well the event can be understood in terms of known pharmacology of the study drug and/or 

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reactions of similar nature previously observed with study drug. Each AE will be assigned one of 
the following five categories: 
• 
Not related: There is not a temporal relationship to the study drug (eg, too early, too 
late), or there is a reasonable causal relationship to another drug, concurrent illness, or 
circumstance. 
• 
Unlikely related: There is a temporal relationship to study drug, but there is not a 
reasonable causal relationship between the time of study drug administration and the AE 
(ie, it is doubtful the AE is related to the study drug); could be reasonably explained by 
other factors, including underlying disease, complications, concomitant drugs, or 
concurrent treatment. 
• 
Possibly related: There is a reasonable temporal sequence from time of study drug 
administration (eg, occurred in a time frame relevant to study drug dose); or for which 
the possibility of the study drug being the causative factor (eg, existence of similar 
reports attributed to the study drug; reactions attributable to the pharmacological effect) 
could not be excluded, although other factors such as underlying disease, complications, 
concomitant drugs, or concurrent treatment are presumable. 
• 
Probably related: There is a reasonable temporal sequence from time of study drug 
administration; and for which the possibility of factors other than the study drug 
administration, such as underlying disease, complications, concomitant drugs, or 
concurrent treatment, could not be excluded as the cause. 
• 
Definitely related: Follows a clear temporal sequence from time of study drug 
administration; could not be possibly explained by the known characteristics of the 
patient’s clinical state, environmental or toxic factors, or other modes of therapy 
administered to the patient; follows a response pattern known to be associated with 
study drug administration. 
10.1.6 Adverse Event Reporting 
Each AE is to be reported by the investigator as serious or non-serious according to the 
definitions in Section 10.1.2 above. This classification determines the regulatory reporting 
procedures to be followed as described in Table 2. 

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Table 2. Reporting Guidelines for Adverse Events 
Gravity of AE  
Reporting Time to  
FPHU/Westat  
Type of Report  
Serious  
Within 24 hours after the site 
becomes aware of the event  
Initial SAE Report  
Non-Serious  
Per AE CRF module  
Completed AE CRF Module 
 
Any SAE, regardless of relationship to investigational therapy that occurs within 28 days 
following the last dose of study drug must be reported to the Medical Monitor within 24 hours 
after the site becomes aware of the event. The investigator is encouraged to discuss with the 
Medical Monitor any adverse experiences for which the issue of reportability is unclear or 
questioned. The initial report should be followed by submission of a more detailed SAE Report 
when follow-up information is available. 
If the SAE occurs more than 28 days after the last dose of study drug, SAEs should be reported 
only if considered related to FF-10502-01. In the event of patient death, the reason for death 
should be recorded as the SAE, with ‘death’ recorded as the outcome on the SAE CRF module. 
The SAE also will be recorded as an AE on the AE CRF module. Note: the SAE Report is 
different from the AE CRF. In areas of both forms where the same data are reported, the forms 
will be completed in a consistent manner. For example, the same term should be used for the 
AE on both forms, with the same start and stop dates, action taken, outcome, etc. A checkbox 
on the AE CRF module for whether the AE resulted in an SAE, will link the two types of report 
for a given event. 
An SAE Report should be prepared with as much available information concerning the event as 
possible so that a written report can be filed with the appropriate regulatory authorities. If 
causality cannot be determined definitively at the time of the SAE occurrence, it is important to 
notify FPHU/Westat within the timeline stated above, and to attribute the relationship as ‘Not 
Assessable’ (only applicable for the initial SAE Report). When new significant information is 
obtained and the outcome and attribution of the event is known, the investigator will 
communicate this in a follow-up SAE Report. This relevant information will be provided in a 
timely manner to allow reporting to regulatory authorities within the required reporting period. 
Any SAE follow-up information requested by FPHU/Westat should be provided in a timely 
manner. 
As necessary, the SAE Report should be accompanied by relevant pages from the CRFs, eg, 
medical history, AEs, concomitant medications. Additional information may be requested by 
FPHU/Westat in an expedited manner to ensure that the initial reporting of the SAE made to the 
regulatory authorities complies with the required time frame. FPHU/Westat may be required to 
collect and report additional information to the regulatory authorities in a follow-up report, 
containing a final evaluation of the event, including copies of hospital reports, autopsy reports, 
or other relevant information. 
10.1.7 Adverse Event and Serious Adverse Event Follow-Up 
All AEs and SAEs should be followed until resolution, return to baseline, or until the point it is 
deemed that further recovery is unlikely. All measures required for AE management and the 
ultimate outcome of the AE will be recorded in the source document and AE CRF module. 

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10.1.8 Ongoing Safety Evaluation 
A study safety evaluation will be conducted on a regular (monthly) basis by teleconference. 
Dose exposure, dose-limiting toxicity, AE/SAE profiles and clinical laboratory abnormalities, and 
other safety measures will be reviewed during each convened meeting. Patient accrual will not 
be interrupted during the regular scheduled safety evaluations. These discussions will be led by 
the FPHU Medical Monitor and Principal Investigator. 
10.1.9 Clinical Laboratory Tests 
Clinical laboratory tests include hematology, coagulation parameters, serum chemistry and 
urinalysis (Table 3). Serum pregnancy testing will be performed at Screening for all women of 
childbearing potential. 
 

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Table 3. Clinical Laboratory Parameters 
Hematology 
Coagulation 
Parameters 
Serum Chemistry 
Urinalysis 
Bone Marrow 
Aspirate/Biopsy 
(Phase 1; 
Lymphoma Patients 
only) 
Red blood cell 
count 
Hemoglobin 
Hematocrit 
White blood cell 
count 
Differential: 
Neutrophils 
ANC 
Lymphocytes (total 
counts for all time 
points; T cell [CD4 
and CD8] and B cell 
counts on Day 1 of 
each cycle and at 
EOT) 
Monocytes 
Eosinophils 
Basophils 
Platelets 
Fibrinogen 
aPTT 
PT (INR) 
Serum creatinine 
BUN 
Glucose (non-
fasting) 
Albumin 
AST 
ALT 
LDH 
Total bilirubin 
Total protein 
Alkaline 
phosphatase 
Calcium 
Phosphorus 
Magnesium 
Sodium 
Potassium 
Chloride 
Bicarbonate 
pH 
Blood 
Nitrates 
Glucose 
Ketones 
Leukocytes 
Protein 
Microscopic 
examination 
Percent cellularity 
Lymphocyte subtype 
Evaluation (eg, 
positive, negative, 
indeterminate) 
Immunohistochemistry 
Cytometry 
Abbreviations: ALT, alanine aminotransferase; aPTT, activated partial thromboplastin time; AST, aspartate 
aminotransferase; BUN, blood urea nitrogen; EOT, end-of-treatment; INR, international normalized ratio; LDH, lactate 
dehydrogenase; PT, prothrombin time. 
10.1.10 
Vital Sign Measurements 
Vital sign measurements include temperature, blood pressure and pulse rate. Additional 
measurements may be obtained if clinically indicated. Any value considered clinically significant 
by the investigator will be recorded as an AE on the CRF. Clinically significant changes 
compared to baseline values should be followed until clinical resolution. 
10.1.11 
Physical Examinations 
Complete physical examinations include the following body system evaluations: General 
Appearance, Skin, Musculoskeletal, Eyes, Ears, Nose, Throat, Cardiovascular, Chest, 
Abdomen, Lymph Nodes, and Neurological. 
Symptom-oriented evaluations will be performed when clinically indicated. Weight will be 
measured at Screening, Day 1 of each treatment cycle and the End of Treatment Visit. 
10.1.12 
Electrocardiograms 
12-Lead ECGs will be performed at Screening and at End of Treatment. 
10.1.13 
Tumor Biopsy 
A tumor biopsy should be obtained at screening or during Cycle 1 in patients with accessible 
tissue, if determined to be feasible, in the opinion of the investigator. The biopsy will be used for 
genetic studies for mutations and other variables to determine tumor molecular subtype which 
can be important for patients who are candidates for personalized therapy. In addition, 
laboratory studies using the tumor tissue may be performed.  

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If the patient’s tumor’s mutation status has already been characterized these data may be 
recorded in the clinical database for further analysis. 
10.2 
Efficacy Assessments 
10.2.1 Criteria for Evaluation of Response and Progression 
Evaluation of response to treatment and determination of disease progression in patients with 
solid tumors will be made according to the Response Evaluation Criteria in Solid Tumors 
(RECIST v. 1.1).1 
10.2.2 Disease Response Criteria 
10.2.2.1 Patients with Solid Tumors 
• 
Evaluation of Target Lesions in Patients with Measurable Disease: 
o Complete Response (CR): Disappearance of all target lesions. Any pathological 
lymph nodes (whether target or non-target) must have reduction in short axis to < 10 
mm. 
o Partial Response (PR): At least a 30% decrease in the sum of the diameters of 
target lesions, taking as reference the baseline sum diameters. 
o Progressive Disease (PD): At least a 20% increase in the sum of the diameters of 
target lesions, taking as reference the smallest sum on study (this includes the 
baseline sum if that is the smallest on study). In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: 
the appearance of one or more new lesions is also considered progression). 
o Stable Disease (SD): Neither sufficient decrease to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while on 
study. 
• 
Evaluation of Non-Target Lesions (all other lesions, or in patients with non-
measurable disease only) 
o Complete Response (CR): Disappearance of all non-target lesions and 
normalization of tumor marker level. All lymph nodes must be non-pathological in 
size (< 10 mm short axis). 
o Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or 
maintenance of tumor marker level above the normal limits. 
o Progressive Disease (PD): Unequivocal progression of existing non-target lesions, 
or appearance of one or more new lesions. When the patient also has measurable 
disease, to achieve ‘unequivocal progression’ on the basis of non-target disease, 
there must be an overall level of substantial worsening in non-target disease such 
that, even in the presence of SD or PR in target disease, the overall tumor burden 
has increased sufficiently to merit discontinuation of therapy. 
• 
Time Point Response 
At each protocol-specified time point, an overall response assessment should be made. 
Criteria for overall response for target and non-target disease are summarized in Table 4 
and Table 5. 
Table 4. Criteria for Overall Response for Target (+/- Non-target) Disease 

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Table 5. Criteria for Overall Response for Non-target Disease Only 
 
• 
Evaluation of Best Overall Response 
The best overall response is the best response recorded across all time points. If CR or 
PR is recorded, confirmation should be sought 28 days later. When SD is believed to be 
the best response, no confirmation is required. 
10.2.3 Efficacy Endpoints 
10.2.3.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients with objective response achieved by 
Week 16 (Cohorts 1 to 12) or Week 12 (Cohort 13) following FF-10502-01 treatment. 
• 
Patients with Solid Tumors 
Objective responses for patients with solid tumors include a best response of complete 
response (CR) or partial response (PR), as defined above. 
10.2.3.2 Secondary Efficacy Endpoints 
Duration of Response: length of time from the date of first evidence of response (CR or PR) to 
date of first evidence of PD 
Duration of SD: length of time from the date of the first administration of study drug to the date 
of first evidence of PD 
Progression-Free Survival: length of time from the date of first administration of study drug to 
the first objective evidence of disease progression or death, whichever is earlier 
Overall Survival: length of time from the date of first administration of study drug to the date of 
death from any cause 

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10.2.4 Timing of Assessments to Determine Response 
Disease assessments will be made at the end of Cycle 2 and every two cycles thereafter. 
Disease assessments may be made at other time points at the discretion of the Investigator. 
10.2.5 Pharmacokinetic Endpoints 
Because a limited number of plasma concentrations will be determined, full determination of 
routine PK parameters may not be possible. In addition to mean plasma concentrations, as the 
data allow, additional PK analyses will be provided (trough levels, t1/2, Tmax, Cmax, AUC, etc). In 
Phase 2a expansion, population PK methods will be utilized to characterize the PK profile of FF-
10502. 
10.2.6 Pharmacodynamic Endpoints 
FF-10502 incorporation into whole blood cellular DNA is expected to increase following 
treatment in a dose dependent manner, based on mechanism of action. Therefore, as a 
measure of pharmacologic activity and a preliminary measure of efficacy, FF-10502 
incorporation into the cellular DNA of whole blood will be assessed and correlated with clinical 
outcome.18 In the Phase 2a expansion, PD data will be combined with PK data to assess the 
impact of drug exposure on FF-10502 incorporation into DNA. 

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11 
STATISTICAL METHODOLOGY 
11.1 
Determination of Sample Size 
Phase 1:  
The sample size reflects requirements associated with a single patient dose escalation until ≥ 
Grade 2 toxicity is observed, thereafter a 3+3 design. A total of 3 to 54 patients are planned (1 
to 6 patients in each of 9 dose cohorts). 
Phase 2a:  
There are 4 cohorts in Phase 2a. The expansion cohorts will assess the efficacy of FF-10502-01 
in a cohort of patients with a variety of solid tumors (Cohort 10), in a cohort of patients with 
cholangiocarcinoma (Cohort 11), in a cohort of patients with gallbladder carcinoma (Cohort 12), 
and in a cohort of patients with urothelial carcinoma (Cohort 13). 
The primary measure of efficacy in these 4 expansion cohorts will be response according to the 
RECIST 1.1. criteria. A maximum of 20 patients will be accrued in Cohort 10, a maximum of 50 
patients will be accrued in Cohort 11, a maximum of 10 patients will be accrued in Cohort 12, 
and a maximum of 27 patients will be accrued into Cohort 13. 
Cohort 10: Cohort 10 will recruit patients with a variety of solid tumors to explore whether 
responses are seen in additional tumor types. If the overall response rate amongst these 
patients is 14%, there will be a less than 5% chance of failing to see a response in at least 
1 patient. 
Cohort 11 (cholangiocarcinoma): Historically, very low response rates have been observed in 
cholangiocarcinoma. Cohort 11, with a maximum of 50 patients, has 80% power if the true 
response rate, p1, is 16%, using a 1-sided type I error of 5% with a null hypothesis, p0, of 5%. A 
Simon 2-stage design will be employed so that 50 patients are only recruited if evidence of 
activity is confirmed at an interim analysis. If after 25 patients have been recruited, there are 1 
or fewer responses, enrollment for this cohort may be suspended for futility. If after 50 patients 
have been recruited, 6 or more responses are observed, the null hypothesis of a 5% response 
rate will be rejected. An alternative analysis may include all treated cholangiocarcinoma 
patients—not just those meeting the definition of Cohort 11. 
Stable disease for ≥ 4 cycles (approximately 4 months) may also be of clinical benefit in this 
population. If the proportion of patients in this cohort having stable disease is ≥30% after 
25 patients have been enrolled and treated, enrollment into this cohort may continue until 50 
patients are treated. Note that recruitment will continue past 25 patients—it will not stop until a 
decision is made at the interim analysis. 
Cohort 12 (gallbladder carcinoma) is exploratory with 10 patients to be recruited. If the 
response rate amongst these patients is 26%, there will be a less than 5% chance of failing to 
see a response in at least 1 patient.  
Cohort 13 (urothelial carcinoma) will also employ a Simon 2-stage design with 80% power, a 
1-sided type I error of 5%, p1 =20% and p0=5%. If after 15 patients have been recruited, there 
are no responses, enrollment for this cohort may be suspended for futility. If after 27 patients 
have been recruited, 4 or more responses are observed, the null hypothesis of a 5% response 
rate will be rejected. 
In both Cohorts 11 and 13, there will be no pause in recruitment prior to the interim analysis 
given the previous responses already observed in these indications. Furthermore, prior to any 

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decision to stop recruitment into a given cohort, the number of patients with prolonged stable 
disease will also be considered.  
 
11.2 
Analysis Populations 
The safety analysis set includes all patients who are administered any fraction of a dose of 
study drug. For a particular measure, the full analysis set (FAS) includes those patients who 
have a valid baseline and one or more post-treatment assessments for that measure of interest. 
The PK population consists of all patients in the FAS who complete a baseline and at least one 
follow-up PK assessment. 
The pharmacodynamic () population consists of all patients in the FAS who complete a baseline 
and at least one follow-up pharmacodynamic assessment. 
11.3 
Statistical Analysis Methods 
All data will be analyzed using Statistical Analysis System (SAS Version 9.4 or higher for 
Windows, SAS Institute, Cary, NC). Continuous variables will be summarized using number, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized using number and frequencies. 
11.3.1 Safety Analyses 
11.3.1.1 Adverse Events 
All safety endpoints will be summarized using descriptive statistics and will be based on the 
safety analysis dataset. 
All AEs will be coded based on the Medical Dictionary for Regulatory Affairs (MedDRA; 
Version 15.0 or higher). An AE will be considered a treatment emergent adverse event (TEAE) if 
the onset is after the first dose of study drug to 28 days following the last dose of study drug or if 
the condition was present at baseline but worsened after the first dose. 
All AEs for each patient will be listed, including intensity grading, relationship to study drug, 
action taken and outcome. Patient listings of deaths, SAEs, and AEs leading to treatment 
discontinuation will be provided. Patient narratives will be provided for deaths, SAEs and other 
significant AEs. Summary tables will be prepared to examine TEAE severity and relationship to 
study treatment. 
AE summaries will be produced separately for each dose cohort and overall, and each disease 
cohort by dose and overall. All summaries will show, dose cohort and overall, the number and 
percentage of patients experiencing at least 1 TEAE of each preferred term, arranged by 
system organ class, and the number of occurrences of the event. Separate summaries will be 
produced by relationship to study drug, by severity, and for those events with an incidence rate 
of at least 2% in any group or overall. 
SAEs will be summarized in a similar manner; overall, by relationship to study drug, and by 
severity. 
In addition to the above, summaries of the number and percentage of patients discontinuing the 
study due to AEs and, due to death, will be presented. 

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11.3.1.2 Laboratory Data 
Laboratory data will be listed by patient. Values above and below normal ranges will be 
indicated, and whether clinically significant. All laboratory values will be graded according to the 
NCI-CTCAE version 4.03 criteria. Laboratory data will be summarized by actual value and 
change from baseline using number of non-missing observations (n), mean, standard deviation, 
median, minimum and maximum. In addition, shift tables and the incidence of Grade 3 or 4 
laboratory values will be presented. 
11.3.1.3 Vital Signs 
Vital signs will be listed by patient. Values above and below normal ranges will be indicated as 
will clinical significance. Vital sign data will be summarized by actual value and change from 
baseline using number of non-missing observations (n), mean, standard deviation, median, 
minimum and maximum. 
11.3.1.4 Other Safety Data 
Data collected for physical examinations, ECGs and related measures will be listed. 
11.3.2 Efficacy Analyses 
11.3.2.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients in each disease cohort 
(cholangiocarcinoma, gallbladder carcinoma, urothelial carcinoma, or other solid tumor) with 
objective response (OR) within 4 cycles of study drug. Thus, this is the proportion of patients in 
Cohorts 1-12 with an OR within 16 weeks of their first dose of study drug and the proportion of 
patients in Cohort 13 with an OR within 12 weeks of their first dose of study drug. The OR rate 
is defined as the proportion of patients in the FAS with a confirmed complete or partial 
response. Ninety percent confidence intervals for the OR rate will be estimated. 
11.3.2.2 Secondary Efficacy Endpoints 
Duration of response, duration of SD, PFS and OS curves will be estimated by disease cohort 
using Kaplan-Meier product limit estimates. Median and 90% confidence interval of time-to-
event will be estimated. Progression-free survival will be calculated from the date of first dose of 
study drug to the date of first documented evidence of disease progression or death, whichever 
is earlier. Overall survival will be calculated from the date of first dose of study drug to the date 
of death due to any cause. Patients who did not experience progression or death will be 
censored at the time of last contact. 
11.3.3 Pharmacokinetic Endpoint Analysis 
Mean plasma concentrations of FF-10502 will be determined at each time point by dose cohort 
for evaluation of dose-linearity. Because a limited number of plasma concentrations will be 
determined, full determination of routine PK parameters may not be possible. In addition to 
mean plasma concentrations, as the data allow, additional PK analyses will be provided (trough 
levels, t1/2, Tmax, Cmax, AUC, etc). Population PK methods will be utilized to characterize the PK 
profile of FF-10502. 
11.3.4 Pharmacodynamic Endpoint Analysis 
Pyrimidine nucleoside anti-metabolites exert their activity via cell-cycle specific cell killing, 
through incorporation into cellular DNA of the target cancer cell. Thus, cells undergoing DNA 
synthesis (S-phase) are killed, and the progression of cells through the G1/S-phase boundary is 
blocked. Accordingly, FF-10502 incorporation into the cellular DNA of whole blood will be 

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determined as a pharmacodynamic endpoint in this study. Change from baseline in FF-10502 
cellular DNA incorporation levels will be measured in whole blood collected from each patient 
during the study. pharmacodynamic parameters from the PD population will be summarized 
using descriptive statistics including the number of patients, mean, standard deviation, 
minimum, median, maximum, range, and coefficient of variation. Changes from baseline will be 
correlated with drug exposure and clinical outcome. 
11.3.5 Other Summaries 
Demographics will be summarized using descriptive statistics. Medical history findings, 
concomitant medications, and protocol deviations will be listed but not summarized. 

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12 
STUDY MANAGEMENT 
12.1 
Data Management 
The investigator is responsible for completing and maintaining adequate and accurate source 
documentation. Source documentation constitutes original records, which may include: progress 
notes, medication administration records, laboratory reports, ECG tracings, discharge 
summaries, CRF worksheets, etc. Data for this study will be submitted electronically. Access to 
the database will be provided following a brief on-line training session. Each user will receive a 
unique username and password, which should not be shared. The investigator must sign the 
investigator’s statement for each patient indicating that the data reported are accurate. See 
APPENDIX H for Ethical Standards to be followed during the study. 
12.2 
Monitoring 
The sponsor and Westat are responsible for ensuring the proper conduct of the study with 
regard to ethics, protocol adherence, site procedures, integrity of the data, and applicable laws 
and/or regulations. At regular intervals during the study and following completion of the study, 
the sponsor’s study monitors will contact the study site via visits to the site, telephone calls, and 
letters in order to review study progress, CRF completion, and address any concerns or 
questions regarding the study conduct. During monitoring visits, the following aspects of study 
conduct will be carefully reviewed: informed consent of patients, patient recruitment, patient 
compliance with the study procedures, source data verification, drug accountability, use of 
concomitant therapy by patients, AE and SAE documentation and reporting, and quality of data. 
Records pertaining to these aspects are expected to be kept current. 
12.3 
Audits and Inspections 
The sponsor, Westat, a regulatory authority, or an IRB may visit the study site at any time during 
the study or after completion of the study to perform audits or inspections. The purpose of a 
sponsor audit or regulatory inspection is to systematically and independently examine all study-
related activities and documents to determine whether these activities were conducted 
according to the protocol, GCP, ICH guidelines, and any other applicable regulatory 
requirements. Investigators should contact FPHU/Westat immediately if contacted by a 
regulatory agency about an inspection at their site. 
12.4 
Amendments 
Any amendments to the protocol will be written and approved by the sponsor. All amendments 
must be submitted to the IRB for approval prior to implementing the changes. In some 
instances, an amendment requires changes to the informed consent form, which also must be 
submitted for IRB approval prior to administration to patients. If any changes to the CRF are 
required, Westat will issue supplemental or revised CRF pages on behalf of the sponsor. 
12.5 
Record Keeping 
12.5.1 Health Insurance Portability Accountability Act of 1996 
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR. Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 [HIPAA] Privacy Regulation). The 
investigator shall ensure that study patients authorize the use and disclosure of protected health 

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information in accordance with HIPAA Privacy Regulation and in a form satisfactory to the 
sponsor. See APPENDIX I for Investigator Obligations. 
12.5.2 Financial Disclosure 
The investigator shall provide to the sponsor sufficient accurate financial information to allow the 
sponsor and Westat to submit complete and accurate financial certification or disclosure 
statements to the FDA. The investigator shall promptly update this information if any relevant 
changes occur in the course of the study or for one year following completion of the study. 
12.5.3 Access to Original Records 
It is an expectation of regulatory authorities that monitors, auditors, and representatives of 
national and international government regulatory agency bodies have access to original source 
documentation to ensure data integrity. “Original” in this context is defined as the first 
documentation of an observation and does not differentiate between hard copy and electronic 
records. 
12.5.4 Retention of Study Documents 
Study-related records must be retained for at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or at least 2 years have elapsed since the formal discontinuation 
of clinical development of the investigational product. These documents should be retained for a 
longer period, however, if required by applicable regulatory requirements or by an agreement 
with the sponsor. 
The investigator must not destroy any study-related records without receiving approval from the 
sponsor. The investigator must notify the sponsor in the event of accidental loss or destruction 
of any study records. If the investigator leaves the institution where the study was conducted, 
the sponsor must be contacted to arrange alternative record storage options. 

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13 
ADMINISTRATIVE STRUCTURE OF THE STUDY 
Westat will be responsible for data management, statistical analyses, and clinical study report 
writing. Clinical monitors under the direction of Westat will be used to monitor the study. Clinical 
laboratory parameters will be assessed by local laboratories and results recorded in the CRF 
module. 

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14 
REFERENCES 
1. 
Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised RECIST guideline 
(version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 
2. 
FF-10502-01 Supplement No. 1 to IB Edition 5.0. March 2018. 
3. 
FF-10502-01 Investigator’s Brochure. December 2017. 
4. 
Biroc, S., Effects of ZK 820973 in the Ames assay. Study No. A14184. Berlex Pharmacology, 2003. 
5. 
Mima, S., In vitro growth inhibition activity of FF-10502-01 in relation to human pancreatic cell 
strains. Study No. FF10502-A01. FUJIFILM Corporation, Pharmaceutical and Research Healthcare 
Laboratories, 2014. 
6. 
Mima, S., In vitro growth inhibition efficacy of FF-10502-01 in relation to human cancer cell strains. 
Study No. FF10502-Z01. FUJIFILM Corporation, Pharmaceutical and Research Healthcare 
Laboratories, 2014. 
7. 
Mima, S., In vitro growth inhibition efficacy of FF-10502-01 in relation to mantle cell lymphoma. Study 
No. FF10502-01Z02. FUJIFILM Corporation, Pharmaceutical and Research Healthcare Laboratories, 
2014. 
8. 
Nozaki, Y., Drug efficacy study in an orthotopic mouse model of pancreatic cancer. Study No. D10-
8125. Japan SLC, Inc., 2014. 
9. 
Nozaki, Y., Anti-tumor effects of FF-10502-01 in a mouse model subcutaneously transplanted with 
the human pancreatic cancer cell line, Capan-1. Study No. D10-8151. Japan SLC, Inc., 2014. 
10. Mima, S., Evaluation of DNA synthesis inhibition by FF-10502-01 in human pancreatic cancer-
derived cell lines. Study No. FF10502-A03. FUJIFILM Corporation, Pharmaceutical and Research 
Healthcare Laboratories, 2014. 
11. Yoshida, K., Assessment of polymerase α inhibitory activity of FF-10502. Study No. AL-5647. 
SEKISUI MEDICAL CO. LTD.ADME & TOX Research Institute, 2014. 
12. Garzon, D., FF-10502-01: A repeat-dose (3 weekly doses) intravenous infusion toxicity study 
followed by a 14-day recovery period in Sprague Dawley rats. Study No. 71983. ITR Laboratories 
Canada, Inc., 2014. 
13. Garzon, D., FF-10502-01: A repeat-dose (3 weekly doses) intravenous infusion toxicity study 
followed by a 14-day recovery period in Beagle dogs. Study No. 61267. ITR Laboratories Canada, 
Inc., 2014. 
14. Liu, X., Evaluation of in vitro plasma protein binding of FF-10502-01 in rat, dog and human plasma. 
Study No. FUJ-2013-002. BRI Biopharmaceutical Research, Inc., 2013. 
15. Leclair, G., Microsomal stability in human, rat, mouse, dog liver microsomes of FF-10502-01. Study 
No. 0307. University of Montreal Platform of Biopharmacy, 2013. 
16. Garzon, D., FF-10502-01: An intravenous infusion dose range-finding toxicity study in Sprague 
Dawley rats. Study No. 71982. ITR Laboratories Canada, Inc., 2013. 
17. Garzon, D., FF-10502-01: An intravenous infusion dose range-finding toxicity study in Beagle dogs. 
Study No. 61266. ITR Laboratories Canada, Inc., 2013. 
18. Wickremsinhe, E.R., et al., Quantification of gemcitabine incorporation into human DNA by 
LC/MS/MS as a surrogate measure for target engagement. Anal Chem, 2010. 82(15): p. 6576-83. 

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15 
APPENDICES 

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APPENDIX A. Eastern Cooperative Group (ECOG) Performance Status Scale 
 

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APPENDIX B. New York Heart Association (NYCA) Classification for Heart Failure 
 

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APPENDIX C. FF-10502-01 Dosing Delays and Dose Modifications 
Treatment may be delayed up to 14 days. If the patient has completed two cycles and, in the 
investigator’s opinion, is receiving benefit, treatment may be delayed for longer than 14 days 
and then resumed following a discussion with the Medical Monitor. Patients who require the 
next treatment cycle to be held for more than 14 days due to ongoing toxicity from the prior 
cycle should have the dose reduced by 25%. 
Patients who experience a toxicity requiring reduction in dose level may continue treatment at 
the lower dose level until disease progression or unacceptable toxicity. The dose level may be 
reduced twice in 25% decrements. For example, if the starting dose was 90 mg/m2, then first 
dose reduction is 67.5 mg/m2, and the 2nd dose reduction is 50 mg/m2. Patients who continue to 
require dose modifications beyond this should be discontinued from the trial. Once the dose has 
been reduced it may not be escalated. 
If a patient experiences myelosuppression, FF-10502-01 should be held and restarted 
according to Table 1. 
Table 1. Dose Modification for Myelosuppression 
Absolute 
Granulocyte Count 
(x 106/L) 
 
Platelet Count 
(x 106/L) 
Action 
≤ 1000 (Grade 3 or 4) Or 
≤ 50,000 (Grade 3 or 
4) 
Dose is held until 
recovery to Grade 2 
or better 
Upon recovery to  
–>1000 (Grade 2, 1 
or normal) 
And 
>50,000 (Grade 2, 1 
or normal) 
Dose may be 75% or 
100% of 
recommended dose 
at investigator 
discretion 
 
Table 2. Dose Modifications for Non-Hematologic Toxicity 
Non-Hematologic Toxicity 
Modification 
Grade ≥ 3 lasting ≤ 7 days 
Withhold dose until ≤ Grade 1, resume next 
dose at 100% 
Grade ≥ 3 lasting > 7 days 
Withhold dose until ≤ Grade 1, resume next 
dose with a 25% reduction 
 

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APPENDIX D. Schedule of Study Procedures 

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Table 6: Schedule of Procedures for Cohorts 1-12 
Study Activity 
Screening1 
Treatment Cycle 1 
Treatment Cycles After 1 
Progression/ 
Relapse 
EOT2 
Long-
term 
FU3 
D1 
D84 
D154  
D224 
D15 
D8 
D15 
End of 
C26,7 
Signed ICD 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
X8 
 
 
 
X8 
 
 
 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
ECOG PS 
X 
X 
 
 
 
X 
 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
X 
 
 
 
 
X 
 
Hematology9 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
CD4, CD8, and 
B-cell counts 
 
X 
 
 
 
X 
 
 
 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum 
chemistry10 
X 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
Urinalysis11 
X 
X 
 
 
 
X 
 
 
 
 
X 
 
β-hCG (WCBP) 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X 
 
Concomitant 
medications 
X 
Continuous 
 
AE assessment 
 
Continuous 
 
Disease 
response 
assessment12 
X 
 
 
 
 
 
 
 
X 
X 
 
 
Blood for PK 
assessment13 
 
X 
 
X 
 
 
 
 
 
 
 
 
Blood for PD 
assessment14 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
FF-10502-01 
administration15 
 
X 
X 
X 
 
X 
X 
X 
 
 
 
 

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Study Activity 
Screening1 
Treatment Cycle 1 
Treatment Cycles After 1 
Progression/ 
Relapse 
EOT2 
Long-
term 
FU3 
D1 
D84 
D154  
D224 
D15 
D8 
D15 
End of 
C26,7 
Survival 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor biopsy 
X16 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; β-hCG, beta human chorionic gonadotropin; C, cycle; CT, computed tomography; D, day; EDTA, ethylenediaminetetraacetic 
acid; ECG, electrocardiogram; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EOT, end of treatment; FU, follow-up; ICD, informed consent 
documentation; MRI, magnetic resonance imaging; PD, pharmacodynamics; PK, pharmacokinetics; WBCP, women of childbearing potential. 
1 Screening to be performed within 28 days before Cycle 1, Day 1. 
2 End of Treatment visit should be 28 days from last dose of study drug (± 5 days). 
3 Long-term follow-up consists of clinic visits or telephone calls every 3 months to assess survival status. 
4 Day 8, 15, or 22 ±1 day. 
5 Day 1 (window ±2 days). 
6 Day 28 ±3 days. 
7 And every 2 cycles thereafter. 
8 Abbreviated physical exam. 
9 Hematology collected at Screening, Cycle 1 Day 1 (only if not performed in the previous 72 hours), Days 8, 15 and 22, Day 1 of each subsequent cycle (within 3 
days of Day 1 of each subsequent cycle), Day 8 and 15 of each cycle (pre-dose) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
10 Serum chemistry collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Days 8, 15 and 22, Day 1 of each subsequent cycle 
(within 3 days of Day 1 of each subsequent cycle) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
11 Urinalysis collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Day 1 of each subsequent cycle (within 3 days of Day 1 of 
each subsequent cycle) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
12 Disease Response Assessment may include CT, MRI, and physical exam. 
13 Peripheral blood collected in EDTA for PK assessment Cycle 1 Day 1, Day 15, pre-dose, immediately following cessation of infusion (within 15 minutes), 
between 1-2 hours post-infusion, and between 4-6 hours post-infusion. 
14 Peripheral blood collected in sodium heparin for PD assessment pre-dose Cycle 1 Days 1, 8, and 15, and during the Day 22 visit. 
15 Prescribed dose (mg/m2) Day 1, 8, 15 of each 28-day cycle. Phase 2a dose is FF-10502-01 90 mg/m2 Day 1, 8, and 15 of each 28-day cycle. 
16 Patients may consent to an optional tumor biopsy during screening or during Cycle 1. (Refer to Section 10.1.13). 
 

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Table 7: Schedule of Procedures for Cohorts 13 
 
Screening1 
Treatment Cycle 1 
Treatment Cycles After 1 
Progression
/ Relapse 
EOT2 
Long-term 
FU3 
Study Activity 
D1 
D84 
D155 
D16 
D8 
End of 
C27,8 
 
 
 
Signed ICD 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
X9 
 
 
X9 
 
 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
 
 
 
X 
 
ECOG PS 
X 
X 
 
 
X 
 
 
 
X 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
 
 
 
X 
 
Hematology10 
X 
X 
X 
X 
X 
X 
 
 
X 
 
CD4, CD8, and B-
cell counts 
 
X 
 
 
X 
 
 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
Serum chemistry11 
X 
X 
X 
X 
X 
 
 
 
X 
 
Urinalysis12 
X 
X 
 
 
X 
 
 
 
X 
 
β-hCG (WCBP) 
X 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
X 
 
Concomitant 
medications 
X 
Continuous 
 
AE assessment 
 
Continuous 
 
Disease response 
assessment13 
X 
 
 
 
 
 
X 
X 
 
 
Blood for PK 
assessment14 
 
X 
X 
 
 
 
 
 
 
 
Blood for PD 
assessment15 
 
X 
X 
X 
 
 
 
 
 
 
FF-10502-01 
administration16 
 
X 
X 
 
X 
X 
 
 
 
 

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Screening1 
Treatment Cycle 1 
Treatment Cycles After 1 
Progression
/ Relapse 
EOT2 
Long-term 
FU3 
Study Activity 
D1 
D84 
D155 
D16 
D8 
End of 
C27,8 
 
 
 
Survival 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor biopsy 
X17 
 
 
 
 
 
 
Abbreviations: AE, adverse event; β-hCG, beta human chorionic gonadotropin; C, cycle; CT, computed tomography; D, day; EDTA, ethylenediaminetetraacetic 
acid; ECG, electrocardiogram; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EOT, end of treatment; FU, follow-up; ICD, informed consent 
documentation; MRI, magnetic resonance imaging; PD, pharmacodynamics; PK, pharmacokinetics; WBCP, women of childbearing potential 
1 Screening to be performed within 28 days before Cycle 1, Day 1. 
2 End of Treatment visit should be 28 days from last dose of study drug (± 5 days). 
3 Long-term follow-up consists of clinic visits or telephone calls every 3 months to assess survival status. 
4 Day 8 ±1 day. 
5 Day 15 ±1 day. 
6 Day 1 (window ±2 days). 
7 Day 21 ±3 days. 
8 And every 2 cycles thereafter. 
9 Abbreviated physical exam. 
10 Hematology collected at Screening, Cycle 1 Day 1 (only if not performed in the previous 72 hours), Days 8, and 15, Day 1 of each subsequent cycle (within 3 
days of Day 1 of each subsequent cycle), Day 8 and 15 of each cycle (pre-dose) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
11 Serum chemistry collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Days 8, and 15, Day 1 of each subsequent cycle 
(within 3 days of Day 1 of each subsequent cycle) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
12 Urinalysis collected at Screening, Cycle 1 Day 1 (only if not performed within the previous 72 hours), Day 1 of each subsequent cycle (within 3 days of Day 1 of 
each subsequent cycle) and End of Treatment. See Table 3 for tests to be conducted at each time point. 
13 Disease Response Assessment may include CT, MRI, and physical exam. 
14 Peripheral blood collected in EDTA for PK assessment Cycle 1 Day 1, Day 8, pre-dose, immediately following cessation of infusion (within 15 minutes), between 
1-2 hours post-infusion, and between 4-6 hours post-infusion. 
15 Peripheral blood collected in sodium heparin for PD assessment pre-dose Cycle 1 Days 1, 8, and during the Day 15 visit. 
16 Prescribed dose (mg/m2) Day 1 and 8 of each 21-day cycle. Phase 2a dose is FF-10502-01 90 mg/m2 Day 1 and 8 of each 21-day cycle. 
17 Patients may consent to an optional tumor biopsy during screening or during Cycle 1. (Refer to Section 10.1.13). 

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APPENDIX E. Ethical Standards 
Ethics and Regulatory Considerations 
This study will be conducted according to Good Clinical Practice (GCP), US 21 Code of Federal 
Regulations (CFR) Part 50, (Protection of Human Subjects), US 21 CFR Part 56 (Institutional 
Review Boards), International council for Harmonisation Guidance for Industry, E6 Good Clinical 
Practice: Consolidated Guidance, the Nuremberg Code, and the Declaration of Helsinki. 
General Instructions 
The U.S. Food and Drug Administration (FDA) regulates studies of drugs, biologics, and 
medical devices. Consequently, these studies are subject to GCP and FDA regulations and 
guidance issued by the FDA and are included in, but not limited to, the following parts of the 
CFR and guideline document: 
• 
21 CFR Part 11 – Electronic Records; electronic signatures 
• 
21 CFR Part 50 – Protection of Human Subjects 
• 
21 CFR Part 54 – Financial Disclosure 
• 
21 CFR Part 56 – Institutional Review Boards 
• 
21 CFR Part 312 – Investigational New Drug Application 
• 
FDA Guidance for Industry: Oversight of Clinical Investigations —A Risk-Based 
Approach to Monitoring, August 2013 
• 
FDA Guidance for IRBs, Clinical Investigators, and Sponsors, June 2010 
• 
FDA Guidance for Industry: Investigator Responsibilities – Protecting the Rights, Safety, 
and Welfare of Study Subjects, October 2009 
• 
FDA Guidance for Industry and Investigators: Safety Reporting Requirements for INDs 
and BA/BE studies, December 2012 
• 
Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance, 2018 
Copies of these materials are available from the sponsor upon request. The purpose of these 
regulations and legal obligations is to define the standards and principles for the proper conduct 
of clinical trials that have been developed by the medical, scientific, and regulatory communities. 
They are not intended to impede or restrict clinical research. 
The ethical standards defined within GCP are intended to ensure that: 
• 
Human subjects are provided with an adequate understanding of the possible risks of 
their participation in the study, and that they have a free choice to participate or not; 
• 
The study is conducted with diligence and in conformance with the protocol in such a 
way as to insure the integrity of the findings; 
• 
The potential benefits of the research justify the risks. 
FPHU is the sponsor of the Investigational New Drug Application (IND). The sponsor, or 
designee, if regulatory obligations have been transferred, is responsible for the following: 
• 
Selecting qualified investigators, 
• 
Providing investigators with the information they need to properly conduct an 
investigation, 

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• 
Ensuring proper monitoring of the investigation, 
• 
Ensuring that the study is conducted according to the general investigational plan and 
protocols contained in the IND, 
• 
Maintaining the IND, and 
• 
Ensuring that FDA and all participating investigators are properly informed of significant 
new information regarding adverse effects or risks associated with the drug being 
studied. 

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APPENDIX F. Investigator Obligations 
Per Title 21 of the US Government Code of Federal Regulations (21 CFR) Parts 50 and 56, the 
study protocol and the final version of the patient informed consent form will be approved by the 
institutional review board (IRB) before enrollment of any patients. The opinion of the IRB will be 
dated and given in writing. A copy of the letter of approval from the IRB and a copy of the 
approved informed consent form will be received by the sponsor prior to shipment of study drug 
supplies to the investigator. 
The investigator will ensure that the IRB will be promptly informed of all changes in the research 
activity and of all unanticipated problems including risk to patients. The investigator will also 
ensure that no changes will be made to the protocol without IRB approval. 
As a part of the IRB requirement for continuing review of approved research, the investigator will 
be responsible for submitting periodic progress reports to the IRB at intervals appropriate to the 
degree of patient risk involved, but no less than once per year. 
Written informed consent must be given freely and obtained from every patient prior to clinical 
trial participation. The rights, safety, and well-being of the trial patients are the most important 
considerations and should prevail over interests of science and society. 
As described in GCP guidelines and FDA regulations, study personnel involved in conducting 
this trial will be qualified by education, training, and experience to perform their respective 
task(s). An FDA Form 1572 will be collected, listing the principal investigator and sub-
investigators involved in the study. Study personnel will not include individuals against whom 
sanctions have been invoked after scientific misconduct or fraud (eg, loss of medical licensure, 
debarment). Quality assurance systems and procedures will be implemented to assure the 
quality of every aspect of the study. 
Informed consent must be obtained from every patient before entry into a clinical study. It must 
be given freely and not under duress. Consent must be documented by use of an IRB-approved 
consent form and signed by the patient or the patient’s legally authorized representative. The 
Department of Health and Human Services suggests that when minors are involved, a parent or 
guardian should sign the consent form. If the minor is an adolescent, his signature should also 
be included. Non-English-speaking patients must be presented with a consent form written in a 
language that they understand. A copy of the signed consent form must be given to the patient 
signing it. Another copy must be kept in the investigator’s files and made available to and FDA 
representatives upon request. If, for any reason, patient risk is increased as the study 
progresses, a revised, IRB-approved consent form must be signed by the patient. Before the 
study begins, a sample of the consent form must be provided to the sponsor for review. The 
FDA may reject otherwise scientifically valid studies if proper informed consent has not been 
obtained from all patients. 
Only in the case of a life-threatening incident may an investigational product be used without 
prior signed consent. In such an emergency situation, separate certifications must be written 
both by a physician not participating in the study and by the investigator. The certifications, 
along with the protocol and informed consent, must be sent to the IRB within 5 working days. In 
this situation, the investigator may not administer any subsequent product to that patient until 
informed consent and IRB approval are obtained. 
Informed Consent 
Written informed consent must be obtained from each patient prior to entry in the study. One 
copy of the signed informed consent document will be given to the patient, and another will be 
retained by the investigator. Additionally, the participant must be allowed adequate time to 

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consider the potential risks and benefits associated with his/her participation in the study. The 
signed and dated consent must be retained with the study records and a copy provided to each 
participant. 
In situations where the participant is not legally competent to provide consent (ie, mentally 
incapacitated), written consent must be obtained from a parent, legal guardian, or legal 
representative. In these situations, the consent must be signed and dated by a witness. 
The informed consent document must have been reviewed and approved by the sponsor and by 
the investigator’s IRB prior to the initiation of the study. The document must contain the eight 
basic elements of informed consent and may contain the six additional elements described in 21 
CFR Part 50. The attached Declaration of Helsinki-provides further details regarding the specific 
requirements for informed consent. Every consent form must include the following eight 
elements: 
• 
A statement that the study involves research, an explanation of the purpose of the 
research and the expected duration of the patient’s participation, a description of the 
procedures to be followed, and identification of any procedures that are experimental  
• 
A description of any reasonably foreseeable risks or discomforts to the patient 
• 
A description of any benefits to the patient or to others that may reasonably be expected 
from the research 
• 
A disclosure of appropriate alternative procedures or course of treatment, if any, that 
might be advantageous to the patient 
• 
A statement describing the extent, if any, to which confidentiality of records identifying 
the patient will be maintained and noting the possibility that the FDA and representatives 
may inspect the records 
• 
An explanation as to whether any compensation or medical treatments are available if 
injury occurs for research involving more than minimal risk. The explanation should 
involve a description of the compensation or treatment available, or a statement 
describing where further information may be obtained 
• 
An explanation of whom to contact for answers to pertinent questions about the research 
and the patient’s rights and whom to contact in the event of a research-related injury 
• 
A statement that participation is voluntary, that refusal to participate will involve no 
penalty or loss of benefits to which the patient is otherwise entitled, and that the patient 
may discontinue participation at any time without penalty or loss of benefits to which the 
patient is otherwise entitled. 
Additional Elements of Informed Consent 
When appropriate, one or more of the following elements of information shall also be included in 
the consent form: 
• 
A statement that the particular treatment or procedure may involve risks to the patient (or 
to the embryo or fetus, if the patient is or may become pregnant) which are currently 
unforeseeable 
• 
Anticipated circumstances under which the patient’s participation may be terminated by 
the investigator without regard to the patient’s consent 
• 
Any additional costs the patient may incur from participation in the research 

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• 
The consequences of a patient’s decision to withdraw from the research and procedures 
for orderly termination of participation by the patient 
• 
A statement that significant new findings developed during the course of the research 
that may relate to the patient’s willingness to continue participation will be provided to 
the patient 
• 
The approximate number of patients involved in the study 
Nothing in these regulations is intended to limit the authority of a physician to provide 
emergency medical care to the extent the physician is permitted to do so under applicable 
federal, state, or local laws. 
The informed consent requirements in these regulations are not intended to preempt any 
applicable federal, state, or local laws that require additional information to be disclosed in order 
that informed consent be legally effective. Some states, such as California and Oregon, require 
further action on the investigator’s part concerning patient consent. 
Institutional Review Board (IRB) Ethic Review Committee (ERC) Review/Approval 
The protocol and informed consent for this study, including advertisements used to recruit 
participants, must be reviewed and approved by an appropriate IRB/ERC prior to enrollment of 
participants in the study. It is the responsibility of the investigator to assure that all aspects of 
the ethical review are conducted in accordance with the current Declaration of Helsinki, 
International council for Harmonization (ICH) Good Clinical Practices, and/or local laws, 
whichever provide the greatest level of protection. A letter documenting the IRB/ERC approval 
which specifically identifies the study/protocol and a list of the committee members must be 
received by the sponsor prior to initiation of the study. Amendments to the protocol will be 
patient to the same requirements as the original protocol. 
A progress report with a request for re-evaluation and re-approval will be submitted by the 
investigator to the IRB/ERC at intervals required by the IRB/ERC, and not less than annually. A 
copy of the report will be sent to the sponsor. 
When the sponsor provides the investigator with a Safety Report, the investigator must promptly 
forward a copy to the IRB/ERC. 
After completion or termination of the study, the investigator will submit a final report to the 
IRB/ERC and to the sponsor, if required. This report should include: deviations from the 
protocol, the number and types of participants evaluated, the number of participants who 
discontinued (with reasons), results of the study, if known, and significant AEs, including deaths 
Study Files 
The investigator is required to maintain complete and accurate study documentation in 
compliance with current Good Clinical Practice standards and all applicable federal, state, and 
local laws, rules, and regulations related to the conduct of a clinical study. 
Patient Confidentiality 
The anonymity of participating patients must be maintained. Patients will be identified by their 
initials and an assigned patient number on CRFs and other documents submitted to the clinical 
monitor. Documents that will be submitted to the clinical monitor and that identify the patient (eg, 
the signed informed consent document) must be maintained in strict confidence by the principal 
investigator, except to the extent necessary to allow auditing by the FDA, the clinical monitor, or 
sponsor personnel. 
Investigational Product Accountability 

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The investigator or designee is responsible for accountability of the investigational product at 
the site. The investigator or designee must maintain records of the product’s delivery to the site, 
inventory at the site, use by each patient, and return to the sponsor or alternative disposition of 
any unused product. These records must include dates, quantities, batch/serial/lot numbers, 
and expiration dates (if applicable). 
The investigator should ensure that the investigational product is used only in accordance with 
the protocol.