Clinical trial NCT04608045
Conditions: Advanced Solid Tumor
Sponsor: CicloMed LLC
Start date: 2019-05-19; Completion date: 2023-04-30
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The expansion study was a Phase I, multicenter, open label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who were scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND).

The Dose Escalation study was a Phase I, multicenter, open label, dose escalation study to evaluate the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or cytologically-confirmed solid tumor type and was completed.

Detailed description:
The expansion cohort of this study was conducted at up to 3 study sites. It was an open-label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who were scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection (PLND). Both cisplatin eligible and chemotherapy eligible MIBC patients scheduled for RC were eligible to participate. Neoadjuvant treatment with CPX-POM, whether alone or in combination with gemcitabine +cisplatin, started within 8 weeks of transurethral resection of the bladder tumor (TURBT) that showed muscularis propria invasion.

Nine patients, four cisplatin-ineligible, and five chemotherapy-eligible patients, were enrolled. Patients who are cisplatin-ineligible were treated with two 21-day treatment cycles of CPX-POM alone (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 treatment, rest days 27-43) before a planned RC. Chemotherapy-eligible patients received neoadjuvant chemotherapy (gemcitabine + cisplatin in three 21-day treatment cycles) in combination with three 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 48-63), i.e. concurrently with the prescribed chemotherapy. The cisplatin + gemcitabine dosing regimen for chemotherapy-eligible patients in the Expansion Cohort was administered per the institution's standard of care. After each infusion of CPX-POM at the RP2D of 900 mg/m2,, patients remained in the clinic for at least a 1-hour observation period. On Day 1 of Cycle 1, single blood and clean catch urine samples were collected prior to the first CPX-POM infusion. On Day 5 of Cycle 1, serial blood and complete urine samples were collected over 24 hours following the fifth, once daily CPX-POM RP2D dose of 900 mg/m2 infused over 20 minutes.

Arms: arm 1: None
Interventions: intervention 1: CPX-POM
Intervention descriptions: intervention 1: CPX-POM

Protocol documents:
Prot_000.pdf: 
 
CicloMed LLC 
 
CLINICAL STUDY PROTOCOL 
 
 
Study Title: 
A Phase 1, First-in-Human, Safety, Dose Tolerance, 
Pharmacokinetics, and Pharmacodynamics Study of CPX-POM 
in Patients with Advanced Solid Tumors 
 
 
Sponsor: 
 
IND No.: 
clinicaltrials.gov Identifier: 
132545 
NCT03348514 
 
 
Indication: 
Advanced Solid Tumors 
 
 
Protocol ID: 
CPX-POM-001 
 
 
Protocol Versions/Dates: 
Original Protocol Version 1.0 / 15 August 2017 
Amendment 1, Version 2.0 / 19 September 2017 
Amendment 2, Version 3.0 / 03 November 2017 
Amendment 3, Version 4.0 / 04 January 2018 
Amendment 4, Version 5.0 / 06 August 2018 
Amendment 4, Version 6.0 / 08 August 2018 
Amendment 4, Version 7.0 / 18 January 2019 
Amendment 5, Version 8.0 / 01 May 2019 
Amendment 6, Version 9.0 / 25 July 2019 (not implemented) 
Amendment 6, Version 10.0 / 20 August 2019 
Amendment 7, Version 11.0 / 16 April 2020 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document, particularly unpublished data, is the property or under control 
of CicloMed LLC, and is provided to you in confidence as an investigator, potential investigator, or 
consultant, for review by you, your staff, and an applicable Institutional Review Board or Independent 
Ethics Committee. The information is only to be used by you in connection with authorized clinical studies 
of the investigational drug described in the protocol. You will not disclose any of the information to others 
without written authorization from CicloMed LLC, except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered. 


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SPONSOR SIGNATURE PAGE 
 
CicloMed LLC  
411 Nichols Rd. 
Suite 217  
Kansas City, MO 64112 
 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid Tumors 
Amendment 7, Version 11.0, 16 April 2020 
This protocol has been approved by CicloMed LLC.  The following signatures document this 
approval. 
 
 
 
 
 
 
 
(Date) 
 
 
 
 
 
  
 
(Date) 


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INVESTIGATOR PROTOCOL AGREEMENT 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid Tumors 
Amendment 7, Version 11.0, 16 April 2020 
 
By my signature, I  
• Confirm that my staff and I have carefully read and understand this protocol and the 
Investigator’s Brochure (IB) and are thoroughly familiar with the appropriate use of 
the investigational drug described herein.   
• Agree to comply with the conduct and terms of the study specified herein and with 
any other study procedures provided by the Sponsor, CicloMed LLC.   
• Agree to comply with US Food and Drug Administration (FDA) regulations, the 
International Conference on Harmonisation (ICH) Good Clinical Practices (GCP) 
guidelines, the Declaration of Helsinki, and all applicable rules, regulations, and 
federal, state, and local laws relating to the conduct of clinical studies and the 
protection of human subjects.  
• Agree not to implement changes to the protocol without agreement from the Sponsor 
and prior written approval (where required) from the Institutional Review Board 
(IRB), except when necessary to eliminate an immediate hazard to the subjects.  
• Agree to onsite monitoring of the case report forms (CRFs) and source documents by 
the Sponsor or designee and to audit by the Sponsor or designee and appropriate 
regulatory authorities, including, but not limited to, the FDA and IRB inspectors. 
• Agree to supervise the conduct of the study and maintain responsibility for training 
and supervising all personnel who have been delegated responsibilities under my 
leadership.  The protocol and other important study materials will be available to 
study staff throughout the conduct of the study. 
 
 
 
Investigator
's Signature 
 
Date 
 
 
 
Print Name 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
 
1. PROTOCOL SUMMARY 
.............................................................................................................................
 
7 
1.1. Synopsis 
............................................................................................................................................
 
7 
1.2. Study Diagram 
................................................................................................................................
 
16 
1.3. Schedules of Assessments 
...............................................................................................................
 
20 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................................ 
33 
2. INTRODUCTION 
.......................................................................................................................................
 
36 
2.1. Background on CPX-POM ............................................................................................................. 
36 
2.2. Background on Bladder Cancer and Rationale for Expansion Cohort 
............................................ 
37 
3. OBJECTIVES ..............................................................................................................................................
 
40 
3.1. Objectives of the Dose Escalation Part of the Study 
....................................................................... 
40 
3.2. Objectives of the Expansion Cohort................................................................................................ 
40 
4. STUDY DESIGN ........................................................................................................................................
 
42 
4.1. Overall Design 
................................................................................................................................
 
42 
4.1.1. 
Design of Dose Escalation Part of the Study 
................................................................. 
42 
4.1.2. 
Design of Expansion Cohort 
......................................................................................... 
45 
4.2. Planned Doses for Dose Escalation 
................................................................................................. 
46 
4.3. Rationale for Study Design 
............................................................................................................. 
47 
4.4. Dose Selection ................................................................................................................................
 
48 
4.5. End of Study Definition 
..................................................................................................................
 
48 
5. STUDY POPULATION 
..............................................................................................................................
 
49 
5.1. Inclusion Criteria ............................................................................................................................
 
49 
5.1.1. 
Inclusion Criteria for Dose Escalation Part of the Study and 
Expansion Cohort 
.......................................................................................................... 
49 
5.1.2. 
Additional Inclusion Criteria for Expansion Cohort Only ............................................ 
50 
5.2. Exclusion Criteria ...........................................................................................................................
 
51 
5.2.1. 
Exclusion Criteria for Dose Escalation Part of the Study ............................................. 
51 
5.2.2. 
Exclusion Criteria for the Expansion Cohort ................................................................ 
52 
5.3. Meals and Dietary Considerations 
.................................................................................................. 
54 
5.4. Screen Failures 
................................................................................................................................
 
54 
6. TREATMENTS 
...........................................................................................................................................
 
55 
6.1. Investigational Product ...................................................................................................................
 
55 
6.1.1. 
Description of Investigational Product 
.......................................................................... 
55 
6.1.2. 
Packaging and Labeling 
................................................................................................ 
55 
6.1.3. 
Storage and Handling 
.................................................................................................... 
55 
6.1.4. 
Dosage and Administration 
........................................................................................... 
55 
6.1.5. 
Dose Modifications 
....................................................................................................... 
56 
6.1.6. 
Compliance ...................................................................................................................
 
56 
6.1.7. 
Accountability 
...............................................................................................................
 
56 
6.2. Prior and Concomitant Medications 
................................................................................................ 
57 
7. DISCONTINUATION OF STUDY INTERVENTION AND PATIENT 
DISCONTINUATION/WITHDRAWAL 
.................................................................................................... 
58 
7.1. Discontinuation of Study Treatment 
............................................................................................... 
58 
7.2. Patient Discontinuation/Withdrawal from the Study ...................................................................... 
58 
7.3. Lost to Follow Up 
...........................................................................................................................
 
58 
8. STUDY ASSESSMENTS ...........................................................................................................................
 
60 
8.1. Cancer Evaluation 
...........................................................................................................................
 
60 
8.1.1. 
Dose Escalation Part of the Study 
................................................................................. 
60 
8.1.2. 
Expansion Cohort 
.......................................................................................................... 
60 
8.2. Safety Assessments 
.........................................................................................................................
 
61 
8.2.1. 
Adverse Events and Serious Adverse Events 
................................................................ 
61 
8.2.2. 
Pregnancy 
......................................................................................................................
 
66 
8.2.3. 
Other Safety and Screening Assessments ..................................................................... 
67 


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8.3. Pharmacokinetic Assessments ........................................................................................................ 
71 
8.4. Pharmacodynamic Assessments 
...................................................................................................... 
71 
8.4.1. 
Dose Escalation Part of the Study 
................................................................................. 
71 
8.4.2. 
Expansion Cohort 
.......................................................................................................... 
72 
9. STATISTICAL CONSIDERATIONS 
......................................................................................................... 
73 
9.1. Number of Patients..........................................................................................................................
 
73 
9.2. Analysis Sets 
...................................................................................................................................
 
73 
9.2.1. 
Safety ............................................................................................................................
 
73 
9.2.2. 
Pharmacokinetics 
.......................................................................................................... 
73 
9.3. Data Handling Conventions 
............................................................................................................ 
73 
9.4. Demographic Data and Baseline Characteristics ............................................................................ 
73 
9.5. Safety Analysis ...............................................................................................................................
 
73 
9.5.1. 
Determination of Maximum Tolerated Dose ................................................................ 
74 
9.5.2. 
Extent of Exposure 
........................................................................................................ 
74 
9.5.3. 
Adverse Events ............................................................................................................. 
74 
9.5.4. 
Laboratory Evaluations 
................................................................................................. 
74 
9.5.5. 
Other Safety Evaluations 
............................................................................................... 
75 
9.6. Pharmacokinetic Analysis 
...............................................................................................................
 
75 
9.6.1. 
Pharmacokinetics in Plasma 
.......................................................................................... 
75 
9.6.2. 
Pharmacokinetics in Urine 
............................................................................................ 
76 
9.6.3. 
Covariates and Pharmacokinetics 
.................................................................................. 
76 
9.7. Pharmacodynamic Analyses 
........................................................................................................... 
76 
9.7.1. 
Dose Escalation Part of the Study 
................................................................................. 
76 
9.7.2. 
Expansion Cohort 
.......................................................................................................... 
77 
9.8. Interim Analyses 
.............................................................................................................................
 
77 
10. REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
.................................... 
78 
10.1. Regulatory and Ethical Considerations 
........................................................................................... 
78 
10.1.1. Institutional Review Board/Ethics Committee 
.............................................................. 
78 
10.1.2. Ethical Conduct of the Study ........................................................................................ 
78 
10.1.3. Informed Consent 
.......................................................................................................... 
79 
10.1.4. Confidentiality .............................................................................................................. 
79 
10.2. Study Oversight ..............................................................................................................................
 
80 
10.2.1. Data Quality Assurance 
................................................................................................. 
80 
10.2.2. Source Documents ........................................................................................................ 
80 
10.2.3. Study and Site Closure 
.................................................................................................. 
80 
10.2.4. Reporting of Results and Publications .......................................................................... 
81 
10.2.5. Study Files and Retention of Records 
........................................................................... 
82 
10.2.6. Case Report Forms 
........................................................................................................ 
83 
10.2.7. Inspections ....................................................................................................................
 
83 
10.2.8. Protocol Compliance 
..................................................................................................... 
83 
10.2.9. Study Discontinuation 
................................................................................................... 
83 
11. REFERENCES 
............................................................................................................................................
 
85 
12. APPENDIX 
..................................................................................................................................................
 
88 
 
 


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LIST OF IN-TEXT TABLES 
Table 1. 
Schedule of Assessments for Dose Escalation Part of Study ........................................ 
21 
Table 2. 
Schedule of Assessments for Expansion Cohort, Cisplatin-
Ineligible Patients 
.......................................................................................................... 
25 
Table 3. 
Schedule of Assessments for Expansion Cohort, Chemotherapy-
Eligible Patients 
............................................................................................................. 
29 
Table 4. 
Dose Escalation Procedures .......................................................................................... 
43 
Table 5. 
Example Doses for Accelerated Titration Cohorts 
........................................................ 
47 
Table 6. 
Example Doses for Standard Dose Escalation Cohorts 
................................................. 
47 
Table 7. 
Eastern Cooperative Performance Status ...................................................................... 
68 
Table 8. 
Listing of Required Screening and Safety Laboratory Parameters 
................................ 
70 
LIST OF IN-TEXT FIGURES 
Figure 1. 
Study Design for Dose Escalation Part of Study 
........................................................... 
17 
Figure 2. 
Study Design for Expansion Cohort, Cisplatin-Ineligible Patients ............................... 
18 
Figure 3. 
Study Design for Expansion Cohort, Chemotherapy-Eligible 
Patients 
..........................................................................................................................
 
19 
LIST OF APPENDICES 
Appendix 1. 
RECIST Criteria Guidance 
............................................................................................ 
88 


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1. 
PROTOCOL
 SUMMARY 
1.1. 
Synopsis 
 
Study Title:  
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, and 
Pharmacodynamics Study of CPX-POM in Patients with Advanced Solid 
Tumors 
IND Number: 
132545 
Study Centers 
Planned: 
Approximately 8-9 centers in the United States 
Objectives: 
Dose Escalation Part 
The primary objective of the Dose Escalation Part of this study is as follows: 
To evaluate the dose limiting toxicities (DLTs) and maximum tolerated dose 
(MTD) of ciclopirox phosphoryloxymethyl ester (CPX-POM) administered 
intravenously (IV) and establish the CPX-POM dose recommended for further 
investigation. 
The secondary objectives of the Dose Escalation Part of this study are as 
follows:  
To characterize the plasma and urine pharmacokinetics (PK) of CPX-POM and 
its metabolites following single and multiple dose administration;  
To identify preliminary anti-tumor activity of CPX-POM;  
To determine urine β-glucuronidase activity in patients participating in the trial. 
The exploratory objectives of the Dose Escalation Part of this study are as 
follows: 
To characterize the pharmacologic effects of CPX-POM on circulating 
biomarkers of Wnt and Notch cell signaling pathways; 
To explore pharmacodynamic (PD) relationships between changes in 
circulating biomarkers and drug and/or metabolites exposure and other 
outcomes. 
Expansion Cohort 
The primary objective of the Expansion Cohort is to determine disease 
response following 2 or 3 CPX-POM treatment cycles by assessing the 
complete and partial pathologic response rate at the time of radical cystectomy 
(RC). 


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The secondary objectives of the Expansion Cohort are as follows: 
• To determine the number of patients with treatment-related adverse events 
(AEs) 
• To elucidate mechanisms of CPX-POM action on bladder tumor tissues 
employing an unbiased approach, using ribonucleic acid sequencing (whole 
transcriptome shotgun sequencing) (RNA-seq) and chromatin 
immunoprecipitation - DNA sequencing (ChIPseq) 
• To determine the change in bladder tumor tissue cell proliferation and 
Notch and Wnt cell signaling pathways via immunohistochemistry 
• To determine the change in bladder tumor tissue CD8+ tumor-infiltrating 
lymphocytes (TIL)  
• To determine recurrence-free survival (RFS) at 2 years post-enrollment  
• To determine the number of patients treated with CPX-POM unable to 
undergo RC  
• To characterize the steady-state plasma and urine PK of CPX-POM, 
ciclopirox (CPX), and ciclopirox glucuronide (CPX-G) 
The exploratory objective of the Expansion Cohort is as follows: 
• To determine urine β-glucuronidase activity 
Study Design: 
This study consists of a Dose Escalation Part and an Expansion Cohort.   
Design of Dose Escalation Part of Study 
The Dose Escalation Part of this study is a first-in-human, Phase 1, multicenter, 
open label, dose escalation study to evaluate the DLTs and MTD and to 
determine the recommended Phase 2 dose (RP2D) of CPX-POM administered 
IV in patients with any histologically- or cytologically-confirmed solid tumor 
type.  Secondary objectives include characterization of the safety and PK 
profile of CPX-POM and identification of preliminary anti-tumor activity in 
this patient population.  Biomarkers and their relationship to PK and other 
outcomes will be examined as an exploratory objective. 
The study will initially employ an accelerated escalation design, with a single 
patient enrolled in each cohort (i.e., Single-Patient Cohorts).  The initial patient 
cohort will receive CPX-POM at a starting dose of 30 mg/m2.  Doses will be 
escalated in 100% increments (i.e., doubling), until a ≥Grade 2 toxicity (with 
the exception of alopecia), as determined according to the United States (US) 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE), version 4.03, is encountered, at which point that cohort and 
all subsequent cohorts will follow a classical “3 + 3” dose escalation design 
(i.e., Standard Dose Escalation Cohorts).   
After each cohort is completed, a Safety Review Committee (SRC) comprised 
of the CRO Medical Monitor, Principal Investigator(s), and Sponsor 
representatives will meet to discuss the data and decide upon the next dose 
escalation.  Doses in the standard cohorts will be escalated in 25 to 50% 
increments, based on SRC decision, until the MTD is reached.  In addition, 
after completion of Cycle 1 for the first 4 to 6 patients, the SRC will review 
safety, PK, and PD data to determine if any changes to the dosing schedule are 
indicated.  
Intrapatient dose escalation will not be allowed in any patient at any time. 


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Each patient in a dose cohort must have received at least 80% of their 
CPX-POM doses, unless due to toxicity, during Cycle 1 with follow-up safety 
evaluations through Day 22 (or Cycle 2, Day 1, if continuing in the study) to be 
eligible for the assessment of DLT.   
Patients may continue to receive cycles of CPX-POM until progression of 
disease, intolerable toxicity occurs, or another withdrawal criterion applies. 
Approximately 24 patients will be enrolled in the Single-Patient and Standard 
Dose Escalation Cohorts to establish the MTD.     
Dose escalation procedures will be conducted as follows:    
 
Accelerated Titration (Single-Patient Cohorts; n=1 each) 
 
No ≥Grade 2 adverse 
events (AEs) 
• Continue evaluation of single-patient dose 
cohorts. 
• Escalate by 100% to next dose level. 
 
At least 1 ≥Grade 2 
AE not meeting the 
definition of DLT 
• Expand current and subsequent cohorts to at least 
3 patients (see Standard Dose Escalation Scheme 
below). 
 
1 DLT  
• Expand current cohort up to 6 patients or until 
2 DLTs are encountered (Standard Dose 
Escalation Scheme below). 
 
Standard Dose Escalation (Standard Cohorts; n=3 to 6 each) 
 
No DLT 
• Escalate by 25−50% to next dose level. 
 
1 DLT in ≤3 patients • Expand cohort up to 6 patients. 
 
1 DLT in 6 patients • Escalate by 25−50% to next dose level. 
 
> 1 DLT in ≤6 
patients 
• MTD reached; stop dose escalation.   
• Possibly explore intermediate doses for the RP2D. 


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A Dose-Limiting Toxicity will be defined as any of the following if deemed 
related to study drug: 
• Grade 4 thrombocytopenia of any duration  
• Grade 3 thrombocytopenia with significant hemorrhage of any duration  
• Grade 4 absolute neutrophil count (ANC) >5 days  
• Febrile neutropenia  
• Grade ≥3 non-hematologic toxicity of any duration, except:  
o Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea 
in the absence of maximal medical therapy that resolves in 72 hours  
o Grade 3 fatigue lasting <5 days 
o Grade 3 hypertension that can be controlled with medical therapy 
o An increase of indirect (unconjugated) bilirubin indicative of 
M. Meulengracht/Gilbert’s syndrome 
o Serum lipase and/or serum amylase CTCAE Grade 3 ≤7 consecutive 
days without clinical signs or symptoms of pancreatitis  
• Delay in study drug due to toxicity for >2 weeks   
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) 
>3xULN with bilirubin >2x the upper limit of normal (ULN) without 
another explanation (e.g., cholestasis)  
Any patient who is unable to receive 80% of the expected dose of CPX-POM 
(i.e., patients who are unable to receive at least 4 of the 5 scheduled doses) 
because of AEs will be considered to have a DLT. 


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Design of Expansion Cohort 
The expansion cohort of this study will be conducted at up to 3 study sites.  It 
will be an open-label feasibility trial to characterize the pharmacologic activity 
of IV CPX-POM in bladder tumor tissues obtained from patients with MIBC 
(Stage ≥T2, N0-N1, M0) who will be scheduled for RC with bilateral (standard 
or extended) pelvic lymph node dissection (PLND).  Approximately half of the 
patients enrolled will be cisplatin-ineligible and half will be chemotherapy-
eligible and scheduled to receive neoadjuvant chemotherapy with gemcitabine 
+ cisplatin.  Neoadjuvant treatment with CPX-POM, whether alone or in 
combination with gemcitabine +cisplatin, will start within 8 weeks of 
transurethral resection of the bladder tumor (TURBT) that showed muscularis 
propria invasion.   
Approximately 12 patients will be enrolled.  Patients who are cisplatin-
ineligible will be treated with two 21-day treatment cycles of CPX-POM 
(Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 treatment, 
rest days 27-43) before a planned RC.  Chemotherapy-eligible patients who are 
scheduled to receive neoadjuvant chemotherapy (gemcitabine + cisplatin in 
three 21-day treatment cycles) will be treated in addition with three 21-day 
treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; 
Cycle 2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 
48-63), i.e. concurrently with the prescribed chemotherapy.  The cisplatin + 
gemcitabine dosing regimen for chemotherapy-eligible patients in the 
Expansion Cohort will be administered per the institution’s standard of care. 
After each infusion of CPX-POM, patients will remain in the clinic for at least 
a 1-hour observation period.  On Day 1 of Cycle 1, single blood and clean-
catch urine samples will be collected prior to the first CPX-POM infusion.  
These pre-treatment samples will serve as patient baseline (or blank) samples to 
check for bioanalytical assay interference.  Following the CPX-POM infusion 
on Cycle 1, Day 5, patients will remain in the clinic for 12 hours following IV 
infusion for serial blood (plasma) and complete 0-12 hour urine sample 
collection.  Patients will be required to return to the clinic the following day, 
Cycle 1, Day 6, for the 24-hour blood (plasma) sample collection as well as to 
return the 12-24 hour urine sample collection container.  Planned RC will be 
performed within approximately 14 days after the end of the second treatment 
cycle (~Day 56) in the case of cisplatin-ineligible patients, and within 14 to 42 
days after the end of the third treatment cycle (~Day 77 to 105 according to 
standard of care) in the case of chemotherapy-eligible patients, or as soon after 
that as is feasible to allow recovery from chemotherapy.   
Bladder Tumor Tissue:  Formalin-fixed, paraffin-embedded bladder tumor 
tissues will be obtained prior to treatment by TURBT and at time of RC for 
characterization of pharmacologic activity.  Archived tumor tissues from 
TURBT may be used.   
Pathologic Response:  Efficacy will be assessed based on the pathologic 
response at the time of RC and evidence of pharmacologic activity in the target 
tissue.  Tumors will be assessed in a standard manner and given grade/stage 
according to the American Joint Commission on Cancer (AJCC) criteria.  
Pathological downstaging will be considered as any tumor with <ypT2N0 
disease. 


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Number of 
Patients 
Planned: 
Dose Escalation Part of Study:  Approximately 24 patients will be enrolled in 
dose escalation cohorts to establish the MTD.   
Expansion Cohort:  Approximately 12 patients will be enrolled in this cohort.  
 
Total:  The total number of patients planned for enrollment in the Dose 
Escalation Part and Expansion Cohort combined is 36. 
Target 
Population: 
Dose Escalation Part of Study: Patients with any histologically- or 
cytologically-confirmed solid tumor type that is refractory to standard therapy.   
Patients should only be included if no therapy exists or if they have received all 
standard therapies that would be potentially curative or might provide 
significant benefit.   
Expansion Cohort:  Patients with MIBC who will be scheduled for RC.  
Approximately half (6) of the patients enrolled will be cisplatin-ineligible and 
half will be chemotherapy-eligible patients with MIBC who are scheduled to 
receive neoadjuvant chemotherapy (i.e., gemcitabine + cisplatin).  
Duration of 
Study: 
Dose Escalation Part of Study: Patients who receive one treatment cycle will be 
in this study for up to approximately 8 weeks:  up to a 28-day Screening period, 
a 21-day Treatment cycle, and a Follow-up period out to 28 ± 5-days after the 
last dose (i.e., approximately Day 33).  After the first treatment cycle, patients 
may continue to receive cycles of CPX-POM until progression of disease, 
intolerable toxicity occurs, or another withdrawal criterion applies.   
Expansion Cohort:  Patents enrolled in this cohort will be in this study for up to 
approximately 2 years and 3 months (for cisplatin-ineligible patients) or 2 years 
and 5 months (for chemotherapy-eligible patients), as follows:   
• Up to a 28-day screening period for all patients 
• A 42-day treatment period for patients who are cisplatin-ineligible or  
A 63-day treatment period for patients who are chemotherapy-eligible.   
• For patients who are cisplatin-ineligible, the treatment period will be 
followed by RC within 14 days.   
For patients who are chemotherapy-eligible and scheduled to receive 
neoadjuvant chemotherapy, the treatment period will be followed by 
RC within 14 to 42 days (according to standard of care), or as soon 
after that as is feasible to allow recovery from chemotherapy.   
• After RC, all patients will be followed for up to 2-years for 
determination of recurrence and survival.  
Diagnosis and 
Main Eligibility 
Criteria: 
Dose Escalation Part of Study: Patients eligible for enrollment in the Dose 
Escalation part of this study will be adults with any histologically- or 
cytologically-confirmed metastatic or advanced-stage solid tumor that is 
refractory to standard therapy.  Patients should only be included if no therapy 
exists or if they have received all standard therapies that would be potentially 
curative or might provide significant benefit.  Patients must have a life 
expectancy ≥3 months, an Eastern Cooperative Oncology Group (ECOG) 
Performance Status 0 or 1, no significant ischemic heart disease, adequate 
hepatic function, and a baseline glomerular filtration rate (GFR) 
>50 mL/min/1.73 m
2.  Females must not be pregnant and, if of childbearing 
potential, must use an effective method of contraception to avoid pregnancy 


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during and for 3 months after participation in the trial.  
Patients who have any risk factor for torsade de pointes or any uncontrolled or 
severe intercurrent medical condition, or who have had major surgery or prior 
systemic chemotherapy or radiation therapy within the previous 4 weeks are 
excluded. 
Expansion Cohort:  Patients eligible for enrollment in the expansion cohort will 
be adults with histologically confirmed MIBC (≥T2, N0-N1, M0 per AJCC) 
pure or mixed histology urothelial carcinoma who are either ineligible for 
cisplatin-based chemotherapy or are eligible to receive neoadjuvant 
chemotherapy with gemcitabine + cisplatin.  Clinical node-positive (N1) 
patients are eligible provided the lymph nodes (LNs) are confined to the true 
pelvis and are within the planned surgical LN dissection template.  Initiation of 
treatment with CPX-POM should be within 8 weeks of TURBT, when feasible.  
Patients must have a life expectancy ≥3 months, an Eastern Cooperative 
Oncology Group (ECOG) Performance Status of 0 or 1, no significant ischemic 
heart disease, adequate hepatic function, and a baseline glomerular filtration 
rate (GFR) >30 mL/min/1.73 m
2.  Females must not be pregnant and, if of 
childbearing potential, must use an effective method of contraception to avoid 
pregnancy during and for 3 months after participation in the trial.  
Patients who have any risk factor for torsade de pointes or any uncontrolled or 
severe intercurrent medical condition, or who have had major surgery or prior 
systemic chemotherapy or radiation therapy within the previous 4 weeks are 
excluded. 
Test Product, 
Dose, and  
Mode of 
Administration: 
Dose Escalation Part of Study:  Escalating doses of CPX-POM will be 
administered by 10-minute IV infusion once daily on Days 1-5 of each 21-day 
cycle.   
After completion of Cycle 1 for the first 4 to 6 patients, the SRC will review 
safety, PK, and PD data to determine if any changes to the dosing schedule are 
indicated (e.g., adding an additional 5 days of dosing to each treatment cycle).   
Patients may continue to receive cycles of CPX-POM until progression of 
disease, intolerable toxicity occurs, or another withdrawal criterion applies.  
The starting dose will be 30 mg/m2.  Investigators should attempt to avoid anti-
emetic medication before and following Dose 1 of Cycle 1 of each treatment 
cohort in order to obtain digital Holter monitoring that will be performed from 
45 minutes pre-dose through 24 hours post-dose without potential influence of 
anti-emetic medications.  Starting with the second dose of study drug, 
investigators may elect to provide anti-emetic prophylaxis or treatment during 
the study.  Care should be taken when utilizing therapies that have a QTc 
liability and the label directions should be followed.  
Expansion Cohort:  Cisplatin-ineligible and chemotherapy-eligible patients 
with MIBC will begin neoadjuvant treatment with CPX-POM within 8 weeks 
after TURBT that showed muscularis propria invasion.  Before a planned RC, 
patients who are cisplatin-ineligible will receive two 21-day treatment cycles of 
CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; Cycle 2, Days 22-26 
treatment, rest days 27-43).  Chemotherapy eligible patients who are scheduled 
to receive neoadjuvant chemotherapy (gemcitabine + cisplatin in three 21-day 
treatment cycles) will be treated in addition and concurrently with three 21-day 
treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; 
Cycle 2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 


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48-63).  CPX-POM will be administered as 900 mg/m2 by 20-minute IV 
infusion once daily to both cisplatin-ineligible and chemotherapy-eligible 
patients with MIBC. 
Reference 
Therapy, Dose, 
and Mode of 
Administration: 
Not applicable. 
Criteria for 
Evaluation: 
Safety (Dose Escalation Part of Study and Expansion Cohort): 
Safety and tolerability will be based on an assessment of AEs, physical 
examinations, vital signs, electrocardiograms (ECGs), clinical laboratory tests, 
ophthalmologic assessments, and concomitant medications.   
The MTD in the Dose Escalation part of the study will be defined as the dose 
BELOW that dose which causes DLTs in ≥33% of patients. 
Pharmacokinetics (Dose Escalation Part of Study): 
Serial blood (plasma) samples and complete urine will be collected over 
24-hour periods starting after the first (Day 1) and fifth (Day 5) doses of 
CPX-POM during Cycle 1 to characterize single dose and steady-state plasma 
and urine PK of CPX-POM, ciclopirox (CPX), and ciclopirox glucuronide 
(CPX-G).  If patients are unable or unwilling to attend the required 12 hours of 
clinic visitation required for steady-state PK sampling on Day 5 of Cycle 1, the 
steady-state PK sampling may be postponed to Day 5 of Cycle 2.  Urine β-
glucuronidase activity will be measured prior to and after 5 days of CPX-POM 
administration (i.e., on Days 1 and 5 of Cycle 1).   
Pharmacokinetics (Expansion Cohort): 
The PK of CPX-POM and metabolites (CPX and CPX-G) will be characterized 
at steady-state during Cycle 1.  Prior to administration of the first CPX-POM 
dose on Cycle 1, Day 1, pre-dose blood (plasma) and urine samples (clean-
catch) will be obtained from each patient.  Immediately prior to and at 0.25, 
0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.9, and 12.0 hours following the IV 
infusion on Cycle 1, Day 5, serial blood (plasma) samples will be collected.  
On Cycle 1, Day 6, patients will return to the clinic for collection of a blood 
(plasma) sample 24 hours following the IV infusion administered on Cycle 1, 
Day 5.  Complete urine will be collected from 0-12 hours and 12-24 hours post-
dose over Days 5-6 of Cycle 1. 
Urine β-glucuronidase activity will be determined from urine samples obtained 
following drug administration on Cycle 1, Days 5-6.  
Pharmacodynamics (Dose Escalation Part of Study): 
Blood will be collected to characterize the effects of CPX-POM on circulating 
biomarkers of Wnt and Notch cell signaling pathways.  Plasma and peripheral 
blood mononuclear cells (PBMCs) will be isolated from blood.  Vascular 
endothelial growth factor (VEGF), interleukin (IL)-6, and IL-8 concentrations 
will be measured in plasma by enzyme-linked immunoassay (ELISA).  
Quantitative real-time polymerase chain reaction (qRT-PCR) will be used to 
characterize gene expression of circulating biomarkers of Wnt and Notch 
signaling pathways in PBMCs. 
Pharmacodynamics (Expansion Cohort): 


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Formalin-fixed, paraffin-embedded bladder tumor tissues obtained prior to 
treatment by TURBT and at time of RC will be used to characterize the 
pharmacologic activity of CPX-POM employing the following assays: 
• immunohistochemistry assays will be performed on prepared pathology 
slides to determine CPX-POM effects on cell proliferation by Ki67, Notch 
and Wnt signaling pathway activity, as well as CD8+ tumor-infiltrating 
lymphocytes (TIL)  
• RNA-seq will be performed on RNA extracted from paraffin-embedded 
tumor tissues, and if appropriate, followed by ChIPseq to identify cell 
signaling pathways and biomarkers up or down-regulated by CPX-POM 
treatment  
Pathological downstaging will be assessed by standard pathological analysis 
and considered as any tumor with <ypT2N0 disease. 
Patients will be followed to determine recurrence and survival for up to 2 years 
post-enrollment.  
Statistical 
Methods: 
Safety, pharmacokinetic, and pharmacodynamic data will be presented 
separately for each part of the study (i.e., the Dose Escalation Part of the study 
and the Expansion Cohort).  
Safety: 
Safety data will be presented in by-patient listings.  Categorical safety 
endpoints will be summarized by frequency of events/abnormalities for each 
dose group and overall.  Continuous safety endpoints will be summarized using 
descriptive statistics (number of subjects [n], mean, standard deviation, median, 
first quartile [Q1], third quartile [Q3], minimum, maximum) for each dose 
group and overall.   
Pharmacokinetics: 
Standard PK parameters will be derived from resultant plasma and urine drug 
and metabolite concentration-time data using non-parametric methods.  PK 
parameters will be summarized using descriptive statistics.   
Pharmacodynamics (Dose Escalation Part of Study): 
A logistic regression will be used to estimate the predicted toxicity probability 
at each dose level.  Relationships between dose, drug and metabolite exposure, 
PD response, and other endpoints (i.e., ECGs, toxicity, safety, and biomarker 
endpoints) may be explored using descriptive statistics, and/or additional 
PK/PD modeling. 
 
Pharmacodynamics (Expansion Cohort): 
The complete (ypT0N0) and partial (<ypT2N0) pathologic response rates at the 
time of RC will be presented in a by-patient listing. 
By-patient listings of the results of bladder tumor tissues analyses by 
immunohistochemistry (Notch, Wnt, CD8+ lymphocyte infiltration, Ki67), 
RNA-seq, and ChIP-seq will be provided. 
Listings of the number of patients treated with CPX-POM who are unable to 
undergo RC will be provided.  
RFS at 2 years post-enrollment will be calculated. 
 


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This study will be conducted in accordance with the guidelines of current GCPs including 
archiving of essential documents.  
1.2. 
Study Diagram 
The study design for the Dose Escalation Part of the study is illustrated in Figure 1,  the 
design of the Expansion Cohort for cisplatin-ineligible patients is illustrated in Figure 2, and 
the design of the Expansion Cohort for patients who receive neoadjuvant chemotherapy 
(gemcitabine + cisplatin) is illustrated in Figure 3. 
 


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Figure 1. 
Study Design for Dose Escalation Part of Study 
 
Abbreviations:  CPX-POM = ciclopirox phosphoryloxymethyl ester; D = day; PD = pharmacodynamic; PK = pharmacokinetic; V = visit. 


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Figure 2. 
Study Design for Expansion Cohort, Cisplatin-Ineligible Patients 
 
Abbreviations: CPX-POM = ciclopirox phosphoryloxymethyl ester; D = day, PK = pharmacokinetics; TURBT = transurethral resection of bladder tumor; V = visit. 
 
 
Study Day:
D -14 
to -1
TURBT that showed muscularis propria lamina 
invasion
Up to 
2 years
Baseline safety and PK assessments, CPX-POM
 dosing
Follow-up
 for
 evaluation
 of
 disease-free
 and
 overall
 survival
 
V1
Study Visit:
D1
V2
V6
Assessment of tumor response and safety follow-up
~D56-
±3
Informed
 consent
 and
 screening
 eligibility
 assessments
 
-8 weeks
D2
V5
D3 D4 D5
V3 V4
Safety assessments, CPX-POM
 dosing
Safety assessments, Steady-state PK, and CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
No dosing or study visits.
D7-
21 
Radical
 cystectomy
 within
 14
 days
 of
 tumor
 assessment
D42-
±3  
Safety assessments, CPX-POM
 dosing
D22
V8
V12
D23
V11
D24D25D26
V9 V10
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
No dosing or study visits.
D27-
43 
Safety assessments, CPX-POM
 dosing
V13
V7
D6
Steady-state
 PK


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Figure 3.  
Study Design for Expansion Cohort, Chemotherapy-Eligible Patients 
 
Abbreviations: CPX-POM = ciclopirox phosphoryloxymethyl ester; D = day, PK = pharmacokinetics; TURBT = transurethral resection of bladder tumor; V = visit. 
Note:  A cisplatin+ gemcitabine dosing regimen will be administered per the institution’s standard of care concurrently with the CPX-POM treatment regimen shown above. 
Study Day:
D -14 
to 
-1
TURBT that showed muscularis propria lamina 
invasion
Up
 to
 
2
 years
Baseline safety and PK assessments, CPX-POM
 dosing
Follow-up
 for
 evaluation
 of
 disease-free
 and
 overall
 survival
 
V1
Study Visit:
D1
V2
V6
Assessment of tumor response and safety follow-up
~D77-
105
Informed
 consent
 and
 screening
 eligibility
 assessments
 
-8 
weeks
D2
V5
D3 D4 D5
V3 V4
Safety assessments, CPX-POM
 dosing
Safety assessments, Steady-state PK, and CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
No CPX-POM dosing or study visits.
(D7-21) 
Radical
 cystectomy
 within
 14
 days
 of
 tumor
 assessment
D64±3
 
 
Safety assessments, CPX-POM
 dosing
D22
V8
V12
D23
V11
D24D25D26
V9V10
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
No CPX-POM dosing or study visits.
(D27-42) 
Safety assessments, CPX-POM
 dosing
V18
V7
D6
Steady-state
 PK
Safety assessments, CPX-POM
 dosing
D43
V13
V17
D44
V16
D45D46D47
V14V15
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
Safety assessments, CPX-POM
 dosing
No CPX-POM dosing or study visits.
(D48--63) 
Safety assessments, CPX-POM
 dosing


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1.3. 
Schedules of Assessments 
The schedule of assessments for the Dose Escalation Part of the study is shown in Table 1, 
the schedule of assessments for Expansion Cohort patients who are cisplatin-ineligible is 
shown in Table 2, and the schedule of assessments for chemotherapy-eligible patients who 
are scheduled to receive neoadjuvant chemotherapy with gemcitabine and cisplatin is shown 
in Table 3. 
 


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Table 1. 
Schedule of Assessments for Dose Escalation Part of Study 
Study Procedure 
Screening 
Period 
Treatment Period 
3 
Follow-up 
Period 
5 
Study Days: 
D -28 to  
D -1 
D1 
1 
D2 
D3 
D4 
D5 1 
D6 
D10 
2  
(Cycle 1 
only) 
D22  
(last cycle) 
4 
28 (±5) days 
post last dose 
or at early 
termination 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
X 
Medical history 
X 
 
 
 
 
 
 
 
 
 
HIV and hepatitis screening 
6 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test 
7 
X 
X 
 
 
 
 
 
 
 
 
Cancer evaluation 8 
X 
X 
 
 
 
 
 
 
 
 
CT or MRI 
X 
 
 
 
 
 
 
 
 
 
MUGA or ECHO 
X 
 
 
 
 
 
 
 
 
 
Hematology 
9 
X 
X 
 
 
X 
 
 
X 
X 
X 
Clinical chemistry 
10 
X 
X 
 
 
X 
 
 
X 
X 
X 
Thyroid panel 
11 
X 
X 
 
 
 
 
 
 
 
 
Coagulation test 
12 
X 
X 
 
 
 
 
 
 
 
 
Urinalysis 
13 
X 
X 
 
 
 
X 
 
X 
X 
X 
Full physical exam 
14 
X 
 
 
 
 
 
 
 
 
X 
Assess for physical 
symptoms/toxicities 
14 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ophthalmologic exam 
15 
X 
 
 
 
 
 
 
 
 
X 
Vital signs 
16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
17 
X 
X 
 
 
 
X 
 
 
 
X 
Start 24- hour Holter monitor 
18 
 
X 
 
 
 
 
 
 
 
 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Study Procedure 
Screening 
Period 
Treatment Period 
3 
Follow-up 
Period 
5 
Study Days: 
D -28 to  
D -1 
D1 
1 
D2 
D3 
D4 
D5 1 
D6 
D10 
2  
(Cycle 1 
only) 
D22  
(last cycle) 
4 
28 (±5) days 
post last dose 
or at early 
termination 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK blood samples 
19 
 
X 
X 
 
 
X 
X 
 
 
 
PK urine samples 
20 
 
X 
X 
 
 
X 
X 
 
 
 
β glucuronidase urine sample 
21 
 
X 
 
 
 
X 
 
 
 
 
Biomarker blood sample 22 
 
X 
 
 
 
X 
 
 
X 
X 
Body surface area 
23 
 
X 
 
 
 
 
 
 
 
 
CPX-POM infusions 24 
 
X 
X 
X 
X 
X 
 
 
 
 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BSA = body surface area; BUN = blood urea nitrogen; CPX-=POM = ciclopirox phosphoryloxymethyl ester; CT = computed tomography; 
D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EDTA = ethylenediamine tetraacetic acid; eGFR = estimated 
glomerular filtration rate; GGT = gamma glutamyl transferase; HIV = human immunodeficiency virus; IV = intravenous; MUGA = multi-gated acquisition; 
MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PK = pharmacokinetic; PT = prothrombin time; 
RBC = red blood cell; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone; V = visit; WBC = white blood cell.   
1. On Days 1 and 5 of Cycle 1, patients will be required to stay at the clinical research unit for at least 12 hours for PK sampling and other 
assessments.  If patients are unable or unwilling to attend the required 12 hours of clinic visitation required for steady-state PK sampling on Day 5 
of Cycle 1, the steady-state PK sampling may be postponed to Day 5 of Cycle 2.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the 
safety laboratory blood samples required for this visit may be drawn up to 3 days before Day 1.  
2. The Day 10 (Visit 8) study visit will only be required during Cycle 1.   
3. After cycle 1; visit windows can be considered on a case by case basis due to events such as holidays; Cycle 1 needs to occur without visit 
windows. D6 can occur +2 calendar days for cycles after Cycle 1 is completed. 
4. If final treatment cycle, patient returns for assessments on Day 22.  If additional cycles are planned, patient skips this visit and restarts schedule at 
Day 1 (except for PK).  Patients may continue to receive cycles of CPX-POM until progression of disease, intolerable toxicity occurs, or another 
withdrawal criterion applies. 
5. The Follow-up visit will occur 28±5 days after the last dose of CPX-POM administered during the last treatment cycle.  Or, in the event that a 
patient discontinues from the study prematurely, the site will make every effort to perform the assessments listed for this study visit.  
6. Hepatitis screening will include tests for Hepatitis A, Hepatitis B, and Hepatitis C.  


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7. Pregnancy tests will be required only for women of childbearing potential at Screening and before dosing on Day 1 of each treatment cycle.  Urine 
or serum pregnancy tests are acceptable.  
8. Cancer evaluation will include determination of staging and metastases for screening purposes (see Section 8.1).  Disease response assessments will 
be performed for patients with measurable disease within 28 days prior to the first dose of CPX-POM and repeated at the end of every second cycle 
(i.e., at approximately 6-week intervals).  During the Dose-Escalation Phase of the study, Screening cancer evaluations may be performed up to 
28 days before Cycle 1, Day 1. 
9. Hematology will include measurement of hemoglobin, hematocrit, platelets, RBC, reticulocytes, and WBC with differential.  To shorten the 
duration of the Cycle 1, Day 1 visit, if needed, the safety laboratory blood samples required for this visit may be drawn up to 3 days before Day 1 
(Cycle 1 only).   
10. Clinical chemistry will include measurement of potassium, sodium, chloride, glucose, BUN, creatinine, creatinine clearance, ALT, AST, ALP, 
GGT, alkaline phosphatase, indirect bilirubin, direct bilirubin, total bilirubin, total protein, albumin, calcium, bicarbonate, magnesium, phosphate, 
lipase, and amylase.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the safety laboratory blood samples required for this visit may 
be drawn up to 3 days before Day 1. 
11. Thyroid panel will include TSH, free T4, and free and total T3 and will be repeated on D1 of each cycle.  
12. Coagulation tests will include PT and aPTT and will be repeated on D1 of each cycle.  
13. Urinalysis will include color, turbidity, pH, specific gravity, glucose, ketones, nitrites, bilirubin, urobilirubin, protein, RBCs, WBCs, epithelial cells, 
casts, crystals, and bacteria, and eGFR at Screening only. 
14. A full physical examination will be conducted at Screening and at Follow-up.  At each other study visit, patients will be assessed for continued 
dosing and any possible physical symptoms/toxicities and a physical examination may be performed, if indicated.  Body weight should be measured 
at each study visit.  Height should be measured at Screening.  
15. Ophthalmology evaluations will be conducted at least on Day 1 and at Follow-up by a qualified ophthalmologist and will include visual acuity, 
pupil exam, confrontation visual field, extraocular motility and alignment, interior slit lamp examination, and dilated fundus examination of the 
retina.  Additional ophthalmology evaluations may be performed at any other time, if indicated, as determined by the investigator.  
16. Vital signs will be measured before any blood draws scheduled for the same time point.  Vital signs will include blood pressure, respiratory rate, 
pulse, oxygen saturation, and temperature.  On Days 1 and 5, vital signs will be measured at pre-dose and at 6-hour intervals post-dose, if possible.  
17. At Screening, 12-lead ECGs will be performed in triplicate, with each measurement separated by 2 minutes.  The average of the 3 screening ECGs 
will be used to calculate QTc interval to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed for all patients prior to drug 
administration on Days 1 and 5 of Cycle 1; on Day 1 of each subsequent treatment cycle; and at the Final Study visit.   
18. Cycle 1:  Starting on Day 1 of Cycle 1, digital Holter monitoring will be performed from 45 minutes pre-dose through 24 hours post-dose.  ECG 
extractions of the continuous Holter recordings will be performed at 45, 30, and 15 minutes pre-dose and at specific post-dose time points 
coinciding with the serial blood sampling time points for pharmacokinetics.  Patients will be instructed to assume a supine position 5-10 minutes 
prior to each serial blood sampling time point and remain supine throughout the 5-minute ECG extraction period just prior to serial blood sample 
collection.  During the 24-hour Holter monitoring period, a 12-lead ECG tracing may be printed out at any time while the patient is in the clinic at 
the discretion of the investigator.  If for any reason Holter monitoring is not performed in conjunction with the PK sampling on Day 1 or the 
tracings are of poor quality, Holter monitoring may be performed in conjunction with the PK sampling on Day 5. 


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19. Cycle 1:  Serial, 3-mL blood samples will be taken for determination of plasma CPX-POM and metabolites concentrations during Cycle 1 prior to 
(pre-dose) and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0, and 24.0 hours following completion of the 10-minute IV infusion on 
Day 1 and on Day 5.  Each PK sample should be collected as close as possible to the planned time.  The 12.0 hour collection can have a +/- 1-hour 
window (collect within 11 to 13 hours) and the exact time must be recorded.  The actual date and time of each blood sample collection will be 
accurately recorded. 
20. Cycle 1:  Complete 24-hour urine samples for determination of CPX-POM and metabolites concentrations, and measurement of urine volume will 
be obtained from each patient in urine collection and storage containers during Cycle 1.  A sample will be taken at pre-dose on Day 1, and complete 
urine samples will be collected at 0-12 and 12-24 hour collection intervals post-dose on Days 1 and 5.  The 12 hour collection can have a +/- 1-hour 
window (collect within 11 to 13 hours) and the exact time must be recorded. 
21. Cycle 1:  Urine β-glucuronidase activity will be determined in the complete 24-hour urine samples collected on Day 1 and Day 5 of Cycle 1.  
22. 7-mL blood samples will be obtained in EDTA-containing blood collection tubes at pre-dose on Day 1 and Day 5 of each treatment cycle, and on 
Day 22 of the last treatment cycle.  Plasma and buffy coat (PBMCs) will be isolated, transferred to storage tubes, and stored frozen. 
23. BSA will be calculated by the site personnel using the Dubois method of calculation using screening height and baseline weight measurements.  
BSA is to be recalculated before study drug administration on Day 1 of every other treatment cycle, starting with Cycle 3 and the patient’s study 
drug dose adjusted accordingly. 
24. CPX-POM infusions will be administered once every 24 hours as 10-minute IV infusions on Days 1-5 of each 21-day treatment cycle.  After 
completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, PK, and PD data to determine if any changes to the dosing schedule 
are indicated (e.g., adding an additional 5 days of dosing to each treatment cycle). 
 


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Table 2. 
Schedule of Assessments for Expansion Cohort, Cisplatin-Ineligible Patients 
Study Procedure 
Screening 
Period 
Treatment Period 
Follow-
up 
Period 
Study Days: 
D -28 to  
D -1 
D1 
1 D2 
D3 
D4 D5 1 D6 D22 D23 D24 D25 D26 
D42 
±3 2 
D56
±3 
Up to 2 
years 
(every 6 
months) 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 V10 V11 V12 
V13/ 
EODT 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis screening 
3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
4 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Evaluate TURBT results 
5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain tumor tissue sample 
6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
MUGA or ECHO 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
7 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
Clinical chemistry 
8 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
Thyroid panel 9 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Coagulation test 
10 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Urinalysis 
11 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Full physical exam 
12 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Assess for physical 
symptoms/toxicities 
12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECG 
14 
X 
X 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
Adverse events 
15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant medications 
16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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Page 26 
Study Procedure 
Screening 
Period 
Treatment Period 
Follow-
up 
Period 
Study Days: 
D -28 to  
D -1 
D1 
1 D2 
D3 
D4 D5 1 D6 D22 D23 D24 D25 D26 
D42 
±3 2 
D56
±3 
Up to 2 
years 
(every 6 
months) 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 V10 V11 V12 
V13/ 
EODT 
 
PK blood samples 
17, 
18 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
PK urine and β-glucuronidase 
sample
17, 19 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Body surface area 
20 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CPX-POM infusions 21 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
Radical cystectomy 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Follow-up for recurrence and 
survival 
22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BSA = body surface area; BUN = blood urea nitrogen; CPX-=POM = ciclopirox phosphoryloxymethyl ester; CT = computed tomography; 
D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EDTA = ethylenediamine tetraacetic acid; eGFR = estimated 
glomerular filtration rate; EODT = end of drug treatment; GGT = gamma glutamyl transferase; HIV = human immunodeficiency virus; IV = intravenous; 
MUGA = multi-gated acquisition; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PK = 
pharmacokinetic; PT = prothrombin time; RBC = red blood cell; RC = radical cystectomy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating 
hormone; V = visit; WBC = white blood cell.   
1. On Days 1 and 5 of Cycle 1, patients will be required to stay at the clinical research unit for at least 12 hours for PK sampling and other 
assessments.  If patients are unable or unwilling to attend the required 12 hours of clinic visitation required for steady-state PK sampling on Day 5 
of Cycle 1, the steady-state PK sampling may be postponed to Day 5 of Cycle 2.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the 
safety laboratory blood samples required for this visit may be drawn up to 3 days before Day 1.  
2. Tumor assessment and safety follow-up assessments will be performed within 14 days (±3 days) after the last cycle.  Or, in the event that a patient 
discontinues from the study prematurely, the site will make every effort to perform the assessments listed for this study visit.  
3. Hepatitis screening will include tests for Hepatitis A, Hepatitis B, and Hepatitis C.  
4. Pregnancy tests will be required only for women of childbearing potential at Screening and before dosing on Day 1 of both treatment cycles.  Urine 
or serum pregnancy tests are acceptable.  
5. Patients must have TURBT results that showed muscularis propria invasion and this should be within 8 weeks prior to Day 1.  
6. Formalin-fixed, paraffin-embedded bladder tumor tissues will be obtained prior to treatment by TURBT and at time of RC for characterization of 
pharmacologic activity.  Archived tumor tissues from TURBT may be used.   


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7. Hematology will include measurement of hemoglobin, hematocrit, platelets, RBC, reticulocytes, and WBC with differential.   
8. Clinical chemistry will include measurement of potassium, sodium, chloride, glucose, BUN, creatinine, creatinine clearance, ALT, AST, ALP, 
GGT, alkaline phosphatase, indirect bilirubin, direct bilirubin, total bilirubin, total protein, albumin, calcium, bicarbonate, magnesium, phosphate, 
lipase, and amylase.   
9. Thyroid panel will include TSH, free T4, and free and total T3 and will be repeated on D1 of each cycle.  
10. Coagulation tests will include PT and aPTT and will be repeated on D1 of each cycle.  
11. Urinalysis will include color, turbidity, pH, specific gravity, glucose, ketones, nitrites, bilirubin, urobilirubin, protein, RBCs, WBCs, epithelial cells, 
casts, crystals, and bacteria, and eGFR at Screening only. 
12. A full physical examination will be conducted at Screening and at Visit 13/Tumor assessment/Safety Follow-up.  At each other study visit, patients 
will be assessed for continued dosing and any possible physical symptoms/toxicities and a physical examination may be performed, if indicated.  
Body weight should be measured at each study visit.  Height should be measured at Screening.  
13. Vital signs will be measured before any blood draws scheduled for the same time point.  Vital signs will include blood pressure, respiratory rate, 
pulse, oxygen saturation, and temperature.  On Days 1 and 5, vital signs will be measured at pre-dose and at 6-hour intervals post-dose, if possible.  
14. At Screening, 12-lead ECGs will be performed in triplicate, with each measurement separated by 2 minutes.  The average of the 3 screening ECGs 
will be used to calculate QTc interval to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed for all patients prior to drug 
administration on Days 1 and 5 of Cycle 1; on the first day of the second treatment cycle; and at the Final Study visit.   
15. All AEs and SAEs will be collected from the signing of the informed consent form through ~28 days after the last dose of study drug (i.e., up to the 
day of cystectomy).  Starting on the day of cystectomy, only AEs related to CPX-POM treatment should be recorded; AEs related to the cystectomy 
procedure will not need to be recorded.  
16. All concomitant medications will be recorded from the time of Screening up to the day of cystectomy.  Starting on the day of cystectomy, only 
medications associated with an AE related to CPX-POM treatment need to be recorded; routine medications and medications associated with the 
cystectomy procedure do not need to be recorded.   
17. Cycle 1, Day 1:  A single, 3-mL, blood sample and clean catch urine sample will be collected prior to the first CPX-POM infusion.  These pre-
treatment samples will serve as patient baseline (or blank) samples to check for bioanalytical assay interference. 
18. Cycle 1, Days 5-6:  Serial, 3-mL blood samples will be taken for determination of steady-state plasma CPX-POM and metabolites concentrations 
during Cycle 1 prior to (pre-dose) and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours following completion of the 20-minute 
IV infusion on Day 5.  On Cycle 1, Day 6, patients will return to the clinic for collection of a blood (plasma) sample 24 hours following the IV 
infusion administered on Cycle 1, Day 5.  Each PK sample should be collected as close as possible to the planned time.  The 12.0- and 24-hour 
collections may have a +/- 1-hour window (collect within 11 to 13 hours or 23 to 25 hours, as applicable) and the exact time must be recorded.  The 
actual date and time of each blood sample collection will be accurately recorded. 
19. Cycle 1, Days 5-6:  Complete 24-hour urine samples for determination of steady-state CPX-POM and metabolites concentrations, and measurement 
of urine volume will be obtained from each patient in urine collection and storage containers during Cycle 1.  A sample will be taken at pre-dose on 
Day 1, and complete urine samples will be collected at 0-12 and 12-24 hour collection intervals post-dose on Days 5 and 6.  The 0-12 hour urine 
collection will be obtained while patients remain in the clinic on Cycle 1, Day 5.  Following collection of the 12-hour blood (plasma) sample and 
0 to 12 hour urine collection on Cycle 1, Day 5, patients will be provided the 12 to 24 hour urine collection container at release from the clinic, 


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instructed to collect all urine at home (overnight and until they return to the clinic on Cycle 1, Day 6), and required to return to the clinic on 
Cycle 1, Day 6 with the 12-24 hour urine collection container.  The 12.0- and 24-hour collections may have a +/- 1-hour window (collect within 
11 to 13 hours or 23 to 25 hours, as applicable) and the exact time must be recorded.  Urine β-glucuronidase activity will be determined in the 
complete 24-hour urine samples collected on Day 5-6 of Cycle 1 
20. BSA will be calculated by the site personnel using the Dubois method of calculation using screening (Visit 1) height and baseline (Visit 2) weight 
measurements.   
21. CPX-POM infusions will be administered as 900 mg/m2 20-minute IV infusion once daily on the first 5 days of each cycle (Days 1-5 and Days 
22-26).  Patients will be observed for at least 1 hour after completion of each infusion of CPX-POM.  
22. Long-term follow-up information may be obtained from the patient’s medical record or may be obtained by telephone call if information is not 
available from the medical records.  
 
 


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CPX-POM 
   
CPX-POM-001, Amendment 7, Version 11.0 
CONFIDENTIAL 
 
Page 29 
Table 3. 
Schedule of Assessments for Expansion Cohort, Chemotherapy-Eligible Patients 
Study Procedure 
Screening 
Period 
Treatment Period 
Follow-
up 
Period 
Study Days: 
D -28 to  
D -1 
D1 
1 D2 
D3 
D4 D5 1 D6 
D22 
and 
D44 
D23 
and 
D45 
D24 
and 
D46 
D25 
and 
D47 
D26 
and 
D48 
D64 
±3 2 
D78
±3 Up to 2 
years 
(every 6 
months) 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
and 
V13 
V9 
and 
V14 
V10 
and 
V15 
V11 
and 
V16 
V12 
and 
V17 
V18/ 
EODT 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis screening 
3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
4 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Evaluate TURBT results 
5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain tumor tissue sample 
6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
MUGA or ECHO 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
7 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
Clinical chemistry 
8 
X 
X 
 
 
X 
 
 
X 
 
 
 
 
X 
 
 
Thyroid panel 9 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Coagulation test 
10 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Urinalysis 
11 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Full physical exam 
12 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Assess for physical 
symptoms/toxicities 
12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECG 
14 
X 
X 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
Adverse events 
15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 


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CONFIDENTIAL 
 
Page 30 
Study Procedure 
Screening 
Period 
Treatment Period 
Follow-
up 
Period 
Study Days: 
D -28 to  
D -1 
D1 
1 D2 
D3 
D4 D5 1 D6 
D22 
and 
D44 
D23 
and 
D45 
D24 
and 
D46 
D25 
and 
D47 
D26 
and 
D48 
D64 
±3 2 
D78
±3 Up to 2 
years 
(every 6 
months) 
Study Visits: V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
and 
V13 
V9 
and 
V14 
V10 
and 
V15 
V11 
and 
V16 
V12 
and 
V17 
V18/ 
EODT 
 
Concomitant medications 
16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
PK blood samples 
17, 
18 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
PK urine and β-glucuronidase 
sample
17, 19 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Body surface area 
20 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CPX-POM infusions 21 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
Radical cystectomy 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Follow-up for recurrence and 
survival 
22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BSA = body surface area; BUN = blood urea nitrogen; CPX-=POM = ciclopirox phosphoryloxymethyl ester; CT = computed tomography; 
D = day; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EDTA = ethylenediamine tetraacetic acid; eGFR = estimated 
glomerular filtration rate; EODT = end of drug treatment; GGT = gamma glutamyl transferase; HIV = human immunodeficiency virus; IV = intravenous; 
MUGA = multi-gated acquisition; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PK = 
pharmacokinetic; PT = prothrombin time; RBC = red blood cell; RC = radical cystectomy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating 
hormone; V = visit; WBC = white blood cell.   
1. On Days 1 and 5 of Cycle 1, patients will be required to stay at the clinical research unit for at least 12 hours for PK sampling and other assessments.  If 
patients are unable or unwilling to attend the required 12 hours of clinic visitation required for steady-state PK sampling on Day 5 of Cycle 1, the steady-
state PK sampling may be postponed to Day 5 of Cycle 2.  To shorten the duration of the Cycle 1, Day 1 visit, if needed, the safety laboratory blood 
samples required for this visit may be drawn up to 3 days before Day 1.  
2. Tumor assessment and safety follow-up assessments will be performed within 14 days (±3 days) after the last cycle.  Or, in the event that a patient 
discontinues from the study prematurely, the site will make every effort to perform the assessments listed for this study visit.  
3. Hepatitis screening will include tests for Hepatitis A, Hepatitis B, and Hepatitis C.  
4. Pregnancy tests will be required only for women of childbearing potential at Screening and before dosing on Day 1 of each treatment cycle.  Urine or 
serum pregnancy tests are acceptable.  


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5. Patients must have TURBT results that showed muscularis propria invasion and this should be within 8 weeks prior to Day 1. 
6. Formalin-fixed, paraffin-embedded bladder tumor tissues will be obtained prior to treatment by TURBT and at time of RC for characterization of 
pharmacologic activity.  Archived tumor tissues from TURBT may be used.   
7. Hematology will include measurement of hemoglobin, hematocrit, platelets, RBC, reticulocytes, and WBC with differential.   
8. Clinical chemistry will include measurement of potassium, sodium, chloride, glucose, BUN, creatinine, creatinine clearance, ALT, AST, ALP, GGT, 
alkaline phosphatase, indirect bilirubin, direct bilirubin, total bilirubin, total protein, albumin, calcium, bicarbonate, magnesium, phosphate, lipase, and 
amylase.   
9. Thyroid panel will include TSH, free T4, and free and total T3 and will be repeated on D1 of each cycle.  
10. Coagulation tests will include PT and aPTT and will be repeated on D1 of each cycle.  
11. Urinalysis will include color, turbidity, pH, specific gravity, glucose, ketones, nitrites, bilirubin, urobilirubin, protein, RBCs, WBCs, epithelial cells, casts, 
crystals, and bacteria, and eGFR at Screening only. 
12. A full physical examination will be conducted at Screening and at Visit 18/Tumor assessment/Safety Follow-up.  At each other study visit, patients will be 
assessed for continued dosing and any possible physical symptoms/toxicities and a physical examination may be performed, if indicated.  Body weight 
should be measured at each study visit.  Height should be measured at Screening.  
13. Vital signs will be measured before any blood draws scheduled for the same time point.  Vital signs will include blood pressure, respiratory rate, pulse, 
oxygen saturation, and temperature.  On Days 1 and 5, vital signs will be measured at pre-dose and at 6-hour intervals post-dose, if possible.  
14. At Screening, 12-lead ECGs will be performed in triplicate, with each measurement separated by 2 minutes.  The average of the 3 screening ECGs will be 
used to calculate QTc interval to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed for all patients prior to drug 
administration on Days 1 and 5 of Cycle 1; on the first day of the second and third treatment cycles; and at the Final Study visit.   
15. All AEs and SAEs will be collected from the signing of the informed consent form through ~28 days after the last dose of study drug (i.e., up to the day of 
cystectomy).  Starting on the day of cystectomy, only AEs related to CPX-POM treatment should be recorded; AEs related to the cystectomy procedure 
will not need to be recorded.  
16. All concomitant medications will be recorded from the time of Screening up to the day of cystectomy.  Starting on the day of cystectomy, only 
medications associated with an AE related to CPX-POM treatment need to be recorded; routine medications and medications associated with the 
cystectomy procedure do not need to be recorded.   
17. Cycle 1, Day 1:  A single, 3-mL, blood sample and clean catch urine sample will be collected prior to the first CPX-POM infusion.  These pre-treatment 
samples will serve as patient baseline (or blank) samples to check for bioanalytical assay interference. 
18. Cycle 1, Days 5-6:  Serial, 3-mL blood samples will be taken for determination of steady-state plasma CPX-POM and metabolites concentrations during 
Cycle 1 prior to (pre-dose) and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, and 12.0 hours following completion of the 20-minute IV infusion on 
Day 5.  On Cycle 1, Day 6, patients will return to the clinic for collection of a blood (plasma) sample 24 hours following the IV infusion administered on 
Cycle 1, Day 5.  Each PK sample should be collected as close as possible to the planned time.  The 12.0- and 24-hour collections may have a +/- 1-hour 
window (collect within 11 to 13 hours or 23 to 25 hours, as applicable) and the exact time must be recorded.  The actual date and time of each blood 
sample collection will be accurately recorded. 
19. Cycle 1, Days 5-6:  Complete 24-hour urine samples for determination of steady-state CPX-POM and metabolites concentrations, and measurement of 
urine volume will be obtained from each patient in urine collection and storage containers during Cycle 1.  A sample will be taken at pre-dose on Day 1, 


CicloMed LLC 
   
Clinical Protocol 
CPX-POM 
   
CPX-POM-001, Amendment 7, Version 11.0 
CONFIDENTIAL 
 
Page 32 
and complete urine samples will be collected at 0-12 and 12-24 hour collection intervals post-dose on Days 5 and 6.  The 0-12 hour urine collection will be 
obtained while patients remain in the clinic on Cycle 1, Day 5.  Following collection of the 12-hour blood (plasma) sample and 0 to 12 hour urine 
collection on Cycle 1, Day 5, patients will be provided the 12 to 24 hour urine collection container at release from the clinic, instructed to collect all urine 
at home (overnight and until they return to the clinic on Cycle 1, Day 6), and required to return to the clinic on Cycle 1, Day 6 with the 12-24 hour urine 
collection container.  The 12.0- and 24-hour collections may have a +/- 1-hour window (collect within 11 to 13 hours or 23 to 25 hours, as applicable) and 
the exact time must be recorded.  Urine β-glucuronidase activity will be determined in the complete 24-hour urine samples collected on Day 5-6 of Cycle 1 
20. BSA will be calculated by the site personnel using the Dubois method of calculation using screening (Visit 1) height and baseline (Visit 2) weight 
measurements.   
21. CPX-POM infusions will be administered as 900 mg/m2 20-minute IV infusion once daily on the first 5 days of each cycle (Days 1-5, Days 22-26, and 
Days 44-48).  Patients will be observed for at least 1 hour after completion of each infusion of CPX-POM.  
22. Long-term follow-up information may be obtained from the patient’s medical record or may be obtained by telephone call if information is not available 
from the medical records.  
 
 


CicloMed LLC 
   
Clinical Protocol 
CPX-POM 
   CPX-POM-001, Amendment 7, Version 11.0 
 
 
CONFIDENTIAL 
 
Page 33 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
adverse event 
AJCC 
American Joint Commission on Cancer 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve following a single dose on Day 1 
AUCss 
area under the concentration-time curve over the dosing interval at steady-
state following drug administration on Day 5 
AUC[0-t] 
area under the concentration-time curve following administration of a 
single dose on Day 1 
AUC[t-∞] 
area under the concentration-time curve following administration of a 
single dose on Day 1 from the last quantifiable concentration (t) to infinity 
AUCinf  
area under the curve from time zero to extrapolated infinite time [AUC
(0-∞)] 
following administration of a single dose on Day 1 as the sum of AUC(0-t) + 
AUC(t-∞) 
BCG 
bacillus Calmette-Guérin 
BSA 
body surface area 
ChIP-seq 
chromatin immunoprecipitation - DNA sequencing 
CLr 
single dose (Day 1) and steady-state (Day 5) renal clearance 
CLs 
systemic clearance following administration of a single dose on Day 1 
CLss 
systemic clearance at steady-state 
Cmax 
the maximum observed plasma concentration of drug and metabolite 
Css
max 
the maximum observed plasma concentration of drug and metabolites 
observed at steady-state over the dosing interval 
CPX 
ciclopirox 
CPX-G 
ciclopirox glucuronide 
CPX-O 
ciclopirox olamine 
CPX-POM 
ciclopirox phosphoryloxymethyl ester (ciclopirox prodrug) 
CRF 
case report form(s) 
CRO 
contract research organization  
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose limiting toxicity 


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CONFIDENTIAL 
 
Page 34 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ELISA 
enzyme-linked immunoassay 
FDA 
(United States) Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practices 
HNSTD 
highest non-serious toxic dose 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
IL 
Interleukin 
IRB 
institutional review board 
IV 
intravenous 
LC-MS/MS 
liquid chromatography tandem mass spectroscopy 
LN 
lymph node 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIBC 
muscle invasive bladder cancer 
mRNA 
messenger RNA 
MTD 
maximum tolerated dose 
MUGA 
multi-gated acquisition 
N 
number of subjects 
NCI 
National Cancer Institute 
NMIBC 
nonmuscle invasive bladder cancer 
NOAEL 
no observed adverse effect level 
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PLND 
pelvic lymph node dissection 
PT 
prothrombin time 
Q1 
first quartile 
Q3 
third quartile 
qRT-PCR 
quantitative real-time polymerase chain reaction 
QTc 
corrected QT interval 


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CONFIDENTIAL 
 
Page 35 
QTcF 
QT interval corrected using Fridericia’s formula 
RC 
radical cystectomy 
RECIST 
Response Evaluation Criteria for Solid Tumors 
RFS 
recurrence-free survival 
RNA 
ribonucleic acid 
RNA-seq 
RNA-sequencing or whole transcriptome shotgun sequencing (use of next-
generation sequencing to reveal the presence and quantity of RNA in a 
biological sample) 
RP2D 
recommended phase 2 dose 
SAE 
serious adverse event 
SOC 
system organ class 
SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reaction 
t
max 
the time (observed time point) of Cmax 
tss
max 
the time (observed time point) of Css
max 
t
½ 
apparent elimination half-life 
ULN 
upper limit of the normal range 
US 
United States 
Vd 
apparent volume of distribution  
VEGF 
vascular endothelial growth factor 
Vss 
Steady-state volume of distribution  
Λ 
apparent first-order elimination rate constant 


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2. 
INTRODUCTION 
2.1. 
Background on CPX-POM 
CPX-POM is a prodrug of ciclopirox (CPX).  CPX is a synthetic antifungal agent approved 
for topical dermatologic use in the treatment of a broad spectrum of fungal organisms 
(Gupta, 2001).  CPX and ciclopirox olamine (CPX-O) are contained in a number of marketed 
topical drug products.  CPX also exerts antibacterial activity against many Gram-positive and 
Gram-negative bacteria (Abrams et al, 1991).  CPX is a hydroxypyridone that is structurally 
unrelated to other antifungal agents and has a unique and complex mode of action.  CPX is 
thought to act through the chelation of polyvalent metal cations, such as iron and aluminum, 
resulting in the inhibition of the metal-dependent enzyme systems (e.g., cytochromes, 
catalase, peroxidase), thus disrupting cellular activities, such as inhibiting degradation of 
peroxides within the fungal cells (Gupta and Plott, 2004) and mitochondrial electron 
transport processes and energy production (Sakurai et al, 1978; Gupta et al, 1994).  It is also 
thought that CPX affects the cytoplasmic membranes, inhibiting transport of essential 
elements in the fungal cell, disrupting the synthesis of DNA, ribonucleic acid (RNA), and 
protein (Gupta and Plott, 2004).  In addition, CPX may have anti-inflammatory activity as 
demonstrated by its ability to inhibit the synthesis of prostaglandins and leukotrienes in 
human polymorphonuclear cells (Abrams et al, 1991) and to inhibit the formation of 
5-lipoxygenase and ciclo-oxygenase (Bohn and Kraemer, 2000; Hanel et al, 1991).   
CPX has demonstrated in vivo and/or in vitro anticancer activity in at least 17 types of solid 
tumor and hematologic cancers (CPX-POM Investigators Brochure, 2017).  CPX modulates 
iron-dependent enzymes and signaling pathways resulting in inhibition of cell growth, 
proliferation, and survival.  CPX has been demonstrated to chelate intracellular iron in 
human cancer cells (Kwong et al, 2015; Eberhard et al, 2009; Sidarovich et al, 2015), which 
plays an important role in cancer cell death resulting from exposure to CPX (Clement et al, 
2002; Szüts and Krude, 2004; Eberhard et al, 2009; Sidarovich et al, 2015).  CPX exposure 
altered expression of 54 proteins in stem cells, including those associated with nucleotide 
binding, biosynthetic processes, gene expression, regulation of transcription, cell cycle 
processes, RNA and messenger RNA (mRNA) processing, and embryonic development 
(Dihazi et al, 2011). 
Scientists at the University of Kansas synthesized the phosphoryloxymethyl ester of CPX, 
CPX-POM to enable parenteral administration of CPX.  In contrast to CPX and CPX-O, 
CPX-POM has high water solubility and is readily formulated for parenteral administration.   
Pharmacokinetic (PK) studies in laboratory animals showed that CPX-POM is rapidly and 
completely metabolized to its active metabolite, CPX, which then disappears from plasma 
following systemic administration of CPX-POM.  Following systemic administration of 


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CPX-POM, the dose is eliminated from the body via renal clearance of CPX and the inactive 
glucuronide metabolite of CPX (CPX-G).   
In rats, intravenous (IV) CPX-POM administered for 28 consecutive days did not cause 
mortality or changes in body weight, food consumption, ophthalmology, hematology, 
coagulation, clinical chemistry, urinalysis, or organ weights.  There were no test item-related 
findings grossly or microscopically at the highest dose level tested (50 mg/kg/day).  Test 
item-related transient clinical signs, including slight to moderate decreased activity, increased 
respiration, eating-like behavior, and slight to moderate incoordination were noted 
immediately after dosing at 50 mg/kg/day.  The no observed adverse effect level (NOAEL) 
in rats was 25 mg/kg/day in males and 50 mg/kg/day in females.  
In dogs, CPX-POM administered for 28 consecutive days did not cause mortality or changes 
in body weight, food consumption, electrocardiogram (ECG) parameters, hematology, 
coagulation, clinical chemistry, urinalysis, or organ weights.  There were no test item-related 
findings grossly or microscopically at dose levels up to 30 mg/kg/day.  Test item-related 
transient clinical signs such as salivation, fecal changes, aggression, shaking, and tremors 
were noted after dosing at the highest dose level tested on the study (30 mg/kg/day).  
Convulsion was apparent in one dog on a single occasion.  Test-item related ophthalmic 
changes were noted in 3/10 dogs treated with 30 mg/kg/day.  Thus, the NOAEL in dogs was 
determined to be 10 mg/kg/day and the highest non-serious toxic dose (HNSTD) in the dog 
was determined to be 30 mg/kg.   
The starting dose of CPX-POM in patients was selected based on the results of the IV 
CPX-POM 28-day Good Laboratory Practices (GLP) toxicology studies conducted in the rat 
and dog and consistent with FDA guidance (FDA, 2010) (see Section 4.4).   
CicloMed is aware of 2 published reports of CPX-O administered orally to humans 
(Minden et al, 2014; Kellner et al, 1981).  Following oral administration of CPX-O to 
patients with refractory hematologic malignancies, evidence of pharmacodynamic (PD) 
activity was observed (Minden et al, 2014; Song et al, 2011).  Administration by the oral 
route of administration, however, is not feasible because of dose-limiting gastrointestinal 
toxicity and poor oral bioavailability due to high first pass effect (Minden et al, 2014).   
2.2. 
Background on Bladder Cancer and Rationale for Expansion Cohort 
The purpose of the Expansion Cohort part of the study is to evaluate the safety and efficacy 
of CPX-POM in patients with muscle invasive bladder cancer (MIBC) who are scheduled to 
undergo radical cystectomy (RC) and who are either cisplatin-ineligible or who eligible for 
and receive neoadjuvant chemotherapy with gemcitabine + cisplatin.  
Bladder cancer is the sixth most common solid tumor in the United States with an estimated 
80, 479 new cases and 17,670 deaths in 2019 (American Cancer Society, 2019).  In 2016, 


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there were an estimated 699,450 people living with this disease in the United States 
(Siegel et al, 2019).  The disease has a high risk of recurrence as well as progression, thus 
requiring life-long surveillance, making bladder cancer the most expensive cancer to treat on 
a per-patient-lifetime-basis (Botteman et al, 2003).  While the overall 5-year survival rate for 
bladder cancer is 77%, in those with advanced disease, this rate can be as low as 4% 
(NCI SEER Cancer Stat Facts, 2019).  
Bladder cancer is defined as two diseases, each with different treatment approaches as well 
as outcomes.  Seventy percent or more of newly diagnosed patients have non-muscle 
invasive bladder cancer (NMIBC) which is generally considered less life-threatening than 
muscle invasive bladder cancer (MIBC) (Heney, 1992).  However, in spite of endoscopic 
resection followed by intravesical immunotherapy (Bacillus Calmette-Guérin [BCG]) or 
chemotherapy (e.g., mitomycin C, gemcitabine), 60 to 70% of those with NMIBC will recur 
and 20 to 30% will progress to MIBC (Aldoursari and Kassouf, 2010), where the gold 
standard treatment is RC coupled with cisplatin-based chemotherapy in either neoadjuvant or 
adjuvant settings (Milan-Rodriguez et al, 2000).  It is estimated, however, that as many as 
40 to 50% of MIBC patients are ineligible for cisplatin chemotherapy due to impaired renal 
function (Dash et al, 2006).  Patients with impaired performance status (ECOG >1), heart 
failure (NYHA class ≥III), grade ≥2 hearing loss, and/or grade ≥2 neuropathy are also 
ineligible for cisplatin-based chemotherapy.  Given the poor complete response rate 
associated with neoadjuvant carboplatin and gemcitabine (Peyton et al, 2018), cisplatin-
ineligible MIBC patients go straight to RC or enroll in clinical trials. 
CPX, the active metabolite of CPX-POM, has been shown to be active against both MIBC 
and NMIBC in vitro.  In vivo, CPX-POM treatment of mice with established bladder tumors 
induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) resulted in robust antitumor 
activity.  More importantly, CPX has been shown to have inhibitory activity against the 
Notch signaling pathway.  Notch overexpression is associated with bladder cancer cell 
growth and survival.  Inhibition of Notch may be an important target for the control of 
bladder cancers.  Finally, currently available agents are administered topically by intravesical 
administration.  Approximately 50% of NMIBC cases will recur within 12 months and 25% 
will progress to MIBC.  CPX-POM affords an opportunity to develop a targeted, 
systemically administered therapy for NMIBC patients who are at risk of progressing to 
MIBC as well as a neoadjuvant treatment for MIBC in cisplatin-ineligible patients. 
CPX-POM potentially has several major advantages over CPX and CPX-O in the context of 
treatment for bladder cancer: 1) CPX-POM represents a composition of matter patentable 
invention; 2) CPX-POM possesses much improved physical and chemical properties that 
enable injectable formulation development; 3) by developing an injectable formulation of 
CPX-POM, CicloMed hopes to avoid the dose-limiting gastrointestinal toxicities and poor 
oral bioavailability observed following oral CPX-O administration; 4) CPX-POM is rapidly 
metabolized to CPX, which is eliminated in the urine as a glucuronide conjugate; 5) elevated 


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beta-glucuronidase activity in the urine of bladder cancer patients has the potential to 
hydrolyze the conjugate back to CPX and thereby affords the potential to target CPX to the 
bladder epithelium; and 6) CPX-POM administered systemically has the potential to deliver 
drug to the entire urinary tract (i.e., to treat upper urinary tract disease), as opposed to agents 
delivered by bladder instillation. 
The Investigator’s Brochure provides further details of the nonclinical studies and published 
clinical evaluations of CPX-POM (CPX-POM Investigator’s Brochure, 2017).  


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3. 
OBJECTIVES 
3.1. 
Objectives of the Dose Escalation Part of the Study 
The primary objective of the Dose Escalation Part of this study is: 
• To evaluate the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) 
of CPX-POM administered IV and establish the CPX-POM dose recommended for 
further investigation. 
The secondary objectives of the Dose Escalation Part of this study are: 
• To characterize the plasma and urine PK of CPX-POM and its metabolites following 
single and multiple dose administration;  
• To identify preliminary anti-tumor activity of CPX-POM;  
• To determine urine β-glucuronidase activity in patients participating in the trial. 
The exploratory objectives of the Dose Escalation Part of this study are: 
• To characterize the pharmacologic effects of CPX-POM on circulating biomarkers of 
Wnt and Notch cell signaling pathways; 
• To explore PD relationships between changes in circulating biomarkers and drug 
and/or metabolites exposure and other outcomes. 
3.2. 
Objectives of the Expansion Cohort 
The primary objective of the Expansion Cohort is to determine disease response following 
2 or 3 CPX-POM treatment cycles by assessing the complete and partial pathologic response 
rate at the time of RC.  
The secondary objectives of the Expansion Cohort are as follows: 
• To determine the number of patients with treatment-related adverse events (AEs) 
• To elucidate mechanisms of CPX-POM action on bladder tumor tissues employing an 
unbiased approach, using ribonucleic acid sequencing (whole transcriptome shotgun 
sequencing; RNA-seq) and chromatin immunoprecipitation - DNA sequencing 
(ChIP-seq) 
• To determine the change in bladder tumor tissue cell proliferation and Notch and Wnt 
cell signaling pathways via immunohistochemistry 


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• To determine the change in bladder tumor tissue CD8+ tumor-infiltrating 
lymphocytes (TIL)  
• To determine recurrence-free survival (RFS) at 2 years post-enrollment  
• To determine the number of patients treated with CPX-POM unable to undergo RC  
• To characterize the steady-state plasma and urine PK of CPX-POM, ciclopirox 
(CPX), and ciclopirox glucuronide (CPX-G) 
The exploratory objective of the Expansion Cohort is as follows: 
• To determine urine β-glucuronidase activity 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This study consists of a Dose Escalation Part and an Expansion Cohort 
4.1.1. 
Design of Dose Escalation Part of the Study 
The Dose Escalation Part of the study is a first-in-human, Phase 1, multicenter, open label, 
dose escalation study to evaluate the DLTs and MTD and to determine the recommended 
Phase 2 dose (RP2D) of CPX-POM administered IV in patients with any histologically- or 
cytologically-confirmed solid tumor type.  Secondary objectives include characterization of 
the safety and PK profile of CPX-POM and identification of preliminary anti-tumor activity 
in this patient population.  Biomarkers and their relationship to PK and other outcomes will 
be examined as an exploratory objective. 
The study will initially employ an accelerated titration design, with a single patient enrolled 
in each cohort (i.e., Single-Patient Cohorts).  The initial patient cohort will receive 
CPX-POM at a starting dose of 30 mg/m2.  Doses will be escalated in 100% increments (i.e., 
doubling), until a ≥Grade 2 toxicity (with the exception of alopecia), as determined according 
to the United States (US) National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE), version 4.03, is encountered, at which point that cohort and all 
subsequent cohorts will follow a classical “3 + 3” dose escalation design (i.e., standard 
cohorts).   
After each Dose Escalation cohort is completed, a Safety Review Committee (SRC) 
comprised of the CRO Medical Monitor, Principal Investigator(s), and Sponsor 
representatives will meet to discuss the data and decide upon the next dose escalation.  Doses 
in the standard cohorts will be escalated in 25 to 50% increments, based on SRC decision, 
until the MTD is reached.  In addition, after completion of Cycle 1 for the first 4 to 
6 patients, the SRC will review safety, PK, and PD data to determine if any changes to the 
dosing schedule are indicated. 
Intrapatient dose escalation will not be allowed in any patient at any time. 
Each patient in a dose cohort must have received at least 80% of their CPX-POM doses, 
unless due to toxicity, during Cycle 1 with follow-up safety evaluations through Day 22 (or 
Cycle 2, Day 1, if continuing in the study) to be eligible for the assessment of DLT.   
Patients may continue to receive cycles of CPX-POM until progression of disease, 
intolerable toxicity occurs, or another withdrawal criterion applies. 


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Approximately 24 patients will be enrolled in the Single-Patient and Standard Dose 
Escalation Cohorts to establish the MTD.   
All patients are to attend a Follow-up Visit 28 days (± 5 days) after the last study drug dose.  
No follow-up after completion of the Follow-up Visit is planned, with the exception of 
monitoring of ongoing treatment-emergent AEs until resolution or until the AE is clearly 
determined to be due to a patient’s stable or chronic condition or intercurrent illness(es). 
Dose escalation procedures will be conducted as shown in Table 4.  For further details and 
example doses, see Section 4.2. 
Table 4. 
Dose Escalation Procedures 
Accelerated Titration (Single-Patient Cohorts; n=1 each) 
No ≥Grade 2 AEs 
• Continue evaluation of single-patient dose cohorts. 
• Escalate by 100% to next dose level. 
At least 1 ≥Grade 2 AE not 
meeting the definition of 
DLT 
• Expand current and subsequent cohorts to at least 3 patients (see 
Standard Dose Escalation Scheme below). 
1 DLT  
• Expand current cohort up to 6 patients or until 2 DLTs are 
encountered (Standard Dose Escalation Scheme below). 
Standard Dose Escalation (Standard Cohorts; n=3 to 6 each) 
No DLT 
• Escalate by 25−50% to next dose level. 
1 DLT in ≤3 patients 
• Expand cohort up to 6 patients. 
1 DLT in 6 patients 
• Escalate by 25−50% to next dose level. 
> 1 DLT in ≤ 6 patients 
• MTD reached; stop dose escalation.   
• Possibly explore intermediate doses for the RP2D. 
 
Abbreviations:  AE = adverse event; DLT = dose limiting toxicity; MTD = maximum tolerated dose; RP2D = 
recommended Phase 2 dose. 
 


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A Dose-Limiting Toxicity will be defined as any of the following, if deemed related to study 
drug: 
• Grade 4 thrombocytopenia of any duration  
• Grade 3 thrombocytopenia with significant hemorrhage of any duration  
• Grade 4 absolute neutrophil count (ANC) greater than 5 days  
• Febrile neutropenia  
• Grade ≥3 non-hematologic toxicity of any duration, except:  
o Grade 3 nausea, vomiting, or diarrhea and Grade 4 vomiting or diarrhea in the 
absence of maximal medical therapy that resolves in 72 hours  
o Grade 3 fatigue lasting <5 days 
o Grade 3 hypertension that can be controlled with medical therapy 
o An increase of indirect (unconjugated) bilirubin indicative of 
M. Meulengracht/Gilbert’s syndrome 
o Serum lipase and/or serum amylase CTCAE Grade 3 ≤7 consecutive days 
without clinical signs or symptoms of pancreatitis  
• Delay in study drug due to toxicity for >2 weeks   
• alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3x the upper limit 
of normal (ULN) with bilirubin >2xULN without another explanation (e.g., 
cholestasis)  
• Any patient who is unable to receive 80% of the expected doses of CPX-POM (i.e., 
patients who are unable to receive at least 4 of the 5 scheduled doses) in Cycle 1 
because of AEs will be considered to have a DLT. 


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4.1.2. 
Design of Expansion Cohort 
The expansion cohort of this study will be conducted at up to 3 study sites.  It will be an 
open-label feasibility trial to characterize the pharmacologic activity of IV CPX-POM in 
bladder tumor tissues obtained from patients with MIBC (Stage ≥T2, N0-N1, M0) who will 
be scheduled for RC with bilateral (standard or extended) pelvic lymph node dissection 
(PLND).  Approximately half (6) of the patients enrolled will be cisplatin-ineligible and half 
will be scheduled to receive neoadjuvant chemotherapy with gemcitabine and cisplatin.  
Neoadjuvant treatment with CPX-POM, whether alone or in combination with gemcitabine 
+cisplatin, will start within 8 weeks of transurethral resection of the bladder tumor (TURBT) 
that showed muscularis propria lamina invasion.   
Approximately 12 patients will be enrolled.  Patients who are cisplatin-ineligible will be 
treated with two 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest 
days 6-21; Cycle 2, Days 22- 26 treatment, rest days 27-43) before a planned RC.  
Chemotherapy-eligible patients who are scheduled to receive neoadjuvant chemotherapy 
(gemcitabine + cisplatin in three 21-day treatment cycles) will be treated in addition with 
three 21-day treatment cycles of CPX-POM (Cycle 1, Days 1-5 treatment, rest days 6-21; 
Cycle 2, Days 22-26 treatment, rest days 27-42; Cycle 3, Days 43-47, rest days 48-63), i.e., 
concurrently with the prescribed chemotherapy.  The cisplatin + gemcitabine dosing regimen 
for chemotherapy-eligible patients in the Expansion Cohort will be administered per the 
institution’s standard of care. 
After each infusion of CPX-POM, patients will remain in the clinic for at least a 1-hour 
observation period.  
On Day 1 of Cycle 1, single blood and clean-catch urine samples will be 
collected prior to the first CPX-POM infusion.  These pre-treatment samples will serve as 
patient baseline (or blank) samples to check for bioanalytical assay interference.  Following 
the CPX-POM infusion on Cycle 1, Day 5, patients will remain in the clinic for 12 hours 
following IV infusion for serial blood (plasma) and complete 0-12 hour urine sample 
collection.  Patients will be required to return to the clinic the following day, Cycle 1, Day 6, 
for the 24-hour blood (plasma) sample collection as well as to return the 12-24 hour urine 
sample collection container.  Planned RC will be performed within approximately 14 days 
after the end of the second treatment cycle (~Day 56) in the case of cisplatin-ineligible 
patients, and within 14 to 42 days after the end of the third treatment cycle (~Day 77 to 105 
according to standard of care) in the case of chemotherapy-eligible patients, or as soon after 
that as is feasible to allow recovery from chemotherapy.   
 
Bladder Tumor Tissue:  Formalin-fixed, paraffin-embedded bladder tumor tissues will be 
obtained prior to treatment by TURBT and at time of RC for characterization of 
pharmacologic activity.  Archived tumor tissues from TURBT may be used.   
Pathologic Response:  Efficacy will be assessed based on the pathologic response at the time 
of RC and evidence of pharmacologic activity in the target tissue.  Tumors will be assessed 
in a standard manner and given grade/stage according to the American Joint Commission on 
Cancer (AJCC) criteria.  Pathological downstaging will be considered as any tumor with 
<ypT2N0 disease. 


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4.2. 
Planned Doses for Dose Escalation 
As described in Sections 4.1, 4.4, and 6.1.4, the starting dose for this study will be 30 mg/m2 
as a 10-minute IV infusion once daily for 5 days, repeated every 21 days.  As stated in 
Section 4.1, the study will initially adopt an accelerated titration design until ≥Grade 2 
toxicity is encountered.  Therefore, as an example, if the first ≥Grade 2 toxicity is not seen 
before the 120 mg/m2 dose level in the early cohorts, then the doses shown in Table 5 may be 
administered.  


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Table 5. 
Example Doses for Accelerated Titration Cohorts 
Cohort 
Daily Dose (mg/m2) 
Number of Patients 
1 
30* 
1 
2 
60 
1 
3 
120 
1 
X 
Until ≥ Grade 2 toxicity 
* In the unlikely event of a DLT at this low dose, up to 5 more patients would be accrued at this dose.  If >1 
DLT was experienced at this dose, a LOWER dose of 15 mg/m2 would be explored in a further cohort. 
Once ≥Grade 2 toxicity is encountered, the standard dose escalation scheme (“3 + 3”) will 
apply and dose escalations will proceed in 25 to 50% increments, although these increments 
may be modified by discussion with the SRC, according to toxicity or other data accrued in 
preceding cohorts.  If, for example, the first ≥Grade 2 toxicity occurs at the 240 mg/m2 dose 
level, the doses shown in Table 6 may be administered.  These doses are EXAMPLES and 
not absolutes until all data from patients in preceding cohorts have been discussed with the 
Principal Investigators and the SRC.  Dose increments generally will be smaller as the MTD 
is thought to be approaching.  
Table 6. 
Example Doses for Standard Dose Escalation Cohorts 
Cohort 
Daily Dose (mg/m2) 
Dose Increase 
Number of Patients 
4 
240 
 
3 - 6 
5 
350  
46% 
3 - 6 
6 
475 
36% 
3 - 6 
X 
? 600  
26% 
3 - 6 
 
All SRC discussions and decisions will be documented and patient safety will be the 
paramount concern. 
4.3. 
Rationale for Study Design 
The primary objective of the Dose Escalation Part of this study is to determine the MTD of 
CPX-POM in cancer patients with advanced solid tumors.  This information will be used to 
inform the selection of the CPX-POM dose to be used in future studies.   
The proposed study design approach is to use a single patient accelerated dose escalation 
until Grade ≥2 toxicity is observed, followed by a conventional 3+3 design in order to 
determine the MTD.  In view of prior human clinical experience with systemic exposure to 
CPX, the use of an accelerated, single patient dose escalation scheme in order to minimize 
patient exposure to suboptimal doses of CPX-POM is warranted. 


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The primary objectives of the Expansion Cohort are to evaluate the safety and efficacy of 
CPX-POM in patients with MIBC who are scheduled to undergo RC.  Approximately half 
(6) of the patients enrolled will be cisplatin-ineligible and half will be chemotherapy-eligible 
patients with MIBC scheduled to receive neoadjuvant chemotherapy (i.e., gemcitabine + 
cisplatin).  The proposed study design approach is to administer the recently-identified MTD 
from the Dose Escalation Part of the study to 12 patients with MIBC who are pre-
cystectomy.  The patient population selected will already have undergone TURBT and will 
be scheduled for RC, and therefore will have tissue samples available for study without 
having to undergo additional, study-specific, invasive procedures.  
4.4. 
Dose Selection 
Food and Drug Administration guidelines (FDA, 2010) were employed to determine the 
starting dose for this study, 30 mg/m2.  As described in this guidance, a common approach 
for determining a starting dose for small molecule drugs is to use one-tenth the severely toxic 
dose in 10% of the animals (STD10) in rodents OR one-sixth the highest non-severely toxic 
dose (HNSTD) in non-rodents.  In GLP toxicology studies in rats, the CPX-POM STD10 was 
not reached, so the highest dose tested (50 mg/kg) was used to determine a safe human 
starting dose of 30 mg/m
2  (one-tenth the STD10 based on mg/m
2).  In GLP toxicology 
studies in dogs, the CPX-POM HNSTD was 10 mg/kg based on tremors and convulsion 
observed at 30 mg/kg.  One-sixth of the HNSTD observed in dogs, converted to mg/m2, also 
supports a starting dose of 30 mg/m2 in patients.  
The dose planned for administration to patients in the Expansion Cohort is the MTD that was 
determined during the Dose Escalation part of the study (cycle[s] of 900 mg/m2 once daily 
for 5 days). 
4.5. 
End of Study Definition 
A patient in the Dose Escalation Part of the study is considered to have completed the study 
if he/she has completed the first cycle of the study.  At the end of the study the patient will 
complete the Day 22 visit as well as the Follow-Up Visit. 
A patient in the Expansion Cohort is considered to have completed the study if he/she has 
completed 2 cycles of CPX-POM treatment (cisplatin-ineligible patients) or 3 cycles of 
CPX-POM treatment (patients scheduled for neoadjuvant chemotherapy with gemcitabine + 
cisplatin) and has undergone RC from which evaluable tissue samples are provided.  Patients 
in the Expansion Cohort will continue to be followed for up to 2 years for determination of 
recurrence and survival.  
The end of the study is defined as the date of the last procedure for the last patient in the 
study.   


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5. 
STUDY POPULATION 
5.1. 
Inclusion Criteria 
5.1.1. 
Inclusion Criteria for Dose Escalation Part of the Study and Expansion 
Cohort 
Patients enrolled in either the Dose Escalation Part or in the Expansion Cohort must meet all 
of the following inclusion criteria to be eligible for participation in this study. 
1. Dose Escalation Cohorts only:  Patient has histologically- or cytologically- confirmed 
metastatic or advanced-stage solid malignant tumor that is refractory to standard 
therapy.  Patients should only be included if no therapy exists or if they have received 
all standard therapies that would be potentially curative or might provide significant 
benefit.  
2. Dose Escalation Cohorts only:  Patient may have received up to 4 prior lines of 
cytotoxic chemotherapy or immunotherapy for their metastatic disease (e.g., 
docetaxel + doxorubicin ± cyclophosphamide), and also may have received additional 
prior endocrine therapy, as appropriate (e.g., for breast or prostate cancer), or non-
myelosuppressive therapy (e.g., bevacizumab, trastuzumab). 
3. Dose Escalation Cohorts only:  Patient has experienced progressive disease during or 
following or was intolerant of their most recent treatment regimen.  Supporting 
information about prior progressive disease will be collected, if available. 
4. Patient is male or female aged ≥18 years. 
5. Patient provided signed and dated informed consent prior to initiation of any study 
procedures. 
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 
(fully active, able to carry out all pre-disease activities without restriction) or 1 
(unable to perform physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature). 
7. Patient has a predicted life expectancy of ≥3 months. 
8. Dose Escalation Cohorts only:  Patient has adequate renal function (creatinine ≤1.5 × 
ULN or a GFR of ≥50 mL/min/1.73 m2). 
Expansion Cohort only:  Patient has a GFR of >30 mL/min/1.73 m2. 


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9. Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 × ULN, 
AST, and /or ALT ≤3 × ULN or ≤5 ×ULN, if due to liver involvement by tumor. 
10. Patient has adequate bone marrow function, as evidenced by hemoglobin ≥9.0 g/dL in 
the absence of transfusion within the previous 72 hours, platelet count 
≥100×109cells/L, and ANC ≥1.5×10
9 cells/L. 
11. Patient has no significant ischemic heart disease or myocardial infarction within 
6 months before the first dose of CPX-POM and currently has adequate cardiac 
function, as evidenced by a left ventricular ejection fraction of >50% as assessed by 
multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and 
corrected QT interval (QTc) <470 msec by Fridericia (QTcF).  The eligibility of 
patients with ventricular pacemakers for whom the QT interval may not be accurately 
measurable will be determined on a case-by-case basis by the Sponsor in consultation 
with the Medical Monitor. 
12. Patient and his/her partner agree to use adequate contraception after providing written 
informed consent through 3 months after the last dose of CPX-POM, as follows: 
a. For women:  Negative pregnancy test during Screening and at Day 1 of each 
treatment cycle and compliant with a medically-approved contraceptive 
regimen during and for 3 months after the treatment period or documented to 
be surgically sterile or postmenopausal. 
b. For men:  Compliant with a medically-approved contraceptive regimen during 
and for 3 months after the treatment period or documented to be surgically 
sterile.  Men whose sexual partners are of child-bearing potential must agree 
to use 2 methods of contraception prior to study entry, during the study, and 
for 3 months after the treatment period. 
13. Patient is willing and able to participate in the study and comply with all study 
requirements. 
5.1.2. 
Additional Inclusion Criteria for Expansion Cohort Only 
14. Patients must have histologically confirmed MIBC (≥T2, N0-N1, M0 per AJCC) pure 
or mixed histology urothelial carcinoma.  Clinical node-positive (N1) patients are 
eligible provided the lymph nodes (LNs) are confined to the true pelvis and are within 
the planned surgical LN dissection template. 
15. The initial TURBT that showed muscularis propria invasion should be within 8 weeks 
prior to beginning study therapy, when feasible.   


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16. Patients must meet one of the following criteria (approximately half of the patients in 
the expansion cohort must meet criterion A below and the other half must meet 
criterion B below):  
A. Patients must be ineligible for cisplatin-based chemotherapy due to any of the 
following: 
• 
Creatinine clearance(CrCl) <60 mL/min with Eastern Cooperative 
Oncology Group (ECOG) Performance Status (PS) 0-1 
• 
Hearing impaired ≥Grade 2 by CTCAE criteria 
• 
Neuropathy ≥Grade 2 by CTCAE criteria 
• 
Heart failure New York Heart Association (NYHA) ≥III 
OR 
B. Patients eligible to receive neoadjuvant chemotherapy with gemcitabine and 
cisplatin prior to cystectomy  
5.2. 
Exclusion Criteria 
5.2.1. 
Exclusion Criteria for Dose Escalation Part of the Study 
Patients who meet any of the following exclusion criteria are not to be enrolled in the Dose 
Escalation Part of this study. 
1. Patient has a history of risk factors for torsade de pointes (e.g., heart failure, 
hypokalemia, family history of long QT syndrome) or requires the use of concomitant 
medications that may significantly prolong the QT/QTc interval during study 
participation.  Patients should not receive anti-emetic medications before and 
following Dose 1 of Cycle 1 for each treatment cohort.  However, anti-emetics such 
as ondansetron or granisetron that have a mild QTc prolonging effect are allowed 
starting with Dose 2 of Cycle 1, if used with caution and attention to the approved 
labelling.  
2. Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or 
computed tomography (CT) scan. 
3. Patient has an uncontrolled or severe intercurrent medical condition (including 
uncontrolled brain metastases).  Patients with stable brain metastases either treated or 
being treated with a stable dose of steroids/anticonvulsants, with no dose change 
within 4 weeks before the first dose of CPX-POM and no anticipated dose change, 
are allowed.  The decision to exclude a patient from the study for an uncontrolled or 
severe intercurrent medical condition will be made by the Principal Investigator.  
Examples could include epilepsy, resistant infection, or any other neurological 
disease that would make clinical assessment difficult. 


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4. Patient underwent major surgery within 4 weeks before the first dose of CPX-POM or 
received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, 
biologic or immunotherapy, etc.) or an investigational drug or device within 4 weeks 
(6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is 
shorter) before the first dose of CPX-POM.  A minimum of 10 days between 
termination of the investigational drug and administration of CPX-POM is required.  
In addition, any drug-related toxicity, with the exception of alopecia, should have 
recovered to ≤Grade 1. 
5. If female, patient is pregnant or breast-feeding. 
6. Patient has evidence of a serious active infection (e.g., infection requiring treatment 
with IV antibiotics). 
7. Patient has active Hepatitis A infection.  
8. Patient known human immunodeficiency virus (HIV) or Hepatitis B or C infection, as 
such patients may be at increased risk for toxicity due to concomitant treatment and 
disease-related symptoms may preclude accurate assessment of the safety of 
CPX-POM. 
9. Patient has an important medical illness or abnormal laboratory finding that, in the 
Investigator’s opinion, would increase the risk of participating in this study. 
10. Patient is taking warfarin.  
11. Patient has a history of other malignancy treated with curative intent within the 
previous 5 years with the exception of adequately treated non-melanoma skin cancer 
or carcinoma in situ of the cervix.  Patients with previous invasive cancers are eligible 
if the treatment was completed more than 5 years prior to initiating current study 
treatment, and there is no evidence of recurrent disease. 
12. Patient has known allergy or hypersensitivity to components of CPX-POM. 
13. Patient is taking any iron replacement therapy administered IV, IM, or orally due to 
the potential for loss of anticancer activity due to drug and/or metabolites chelating 
iron. 
5.2.2. 
Exclusion Criteria for the Expansion Cohort 
Patients who meet any of the following exclusion criteria are not to be enrolled in the 
Expansion Cohort of this study. 
1. Baseline GFR <30 mL/min/1.73 m2. 


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2. Women must not be pregnant or breastfeeding since we do not know the effects of 
CPX-POM on the fetus or breastfeeding child. 
3. Patients may not have concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive 
urothelial carcinoma.  Patients with history of non-invasive (Ta, Tis) upper tract 
urothelial carcinoma that has been definitively treated with at least one post-treatment 
disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of 
residual disease are eligible. 
4. Patients may not have another malignancy that could interfere with the evaluation of 
safety or efficacy of the study drugs.  Patients with a prior malignancy will be 
allowed without study chair approval in the following circumstances: 
a. Not currently active and diagnosed at least 3 years prior to the date of 
registration. 
b. Non-invasive diseases such as low risk cervical cancer or any cancer in situ. 
c. Localized (early stage) cancer treated with curative intent (without evidence 
of recurrence and intent for further therapy), and in which no chemotherapy 
was indicated (e.g. low/intermediate risk prostate cancer, etc.). 
5. Patients may not have undergone major surgery with the exception of TURBT (e.g. 
intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic 
injury or specific anti-cancer treatment ≤4 weeks prior to starting study drug, or 
patients who have had percutaneous biopsies or placement of vascular access device 
≤1 week prior to starting study drug, or who have not recovered from side effects of 
such procedure or injury. 
6. Patients must not have clinically significant cardiac disease. 
7. Patients may not have chronic active liver disease or evidence of acute or chronic 
Hepatitis B Virus (HBV) or Hepatitis C (HCV). 
8. Patients may not have known diagnosis of human immunodeficiency virus (HIV) 
infection.  Testing is not required in absence of clinical suspicion. 
9. Patients may not have known diagnosis of any condition (e.g. post-hematopoietic or 
solid organ transplant, pneumonitis, inflammatory bowel disease, etc.) that requires 
chronic immunosuppressive therapy.  Usage of non-steroidal anti-inflammatory 
medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis 
inhibitors for the treatment of gout are permitted. 
10. Patients with any serious and/or uncontrolled concurrent medical conditions (e.g., 
active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that 
could, in the investigator
's opinion, cause unacceptable safety risks or potentially 
interfere with the completion of the treatment according to the protocol are not 
eligible. 
11. Patients may not have any live viral vaccine used for prevention of infectious diseases 
within 4 weeks prior to study drug(s). 
12. Patients unwilling or unable to comply with the protocol. 


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5.3. 
Meals and Dietary Considerations 
On Days 1 and 5 of Cycle 1, patients in the Dose Escalation Part of the study will be required 
to stay at the clinical research unit for at least 12 hours for PK sampling and other 
assessments.  Patients will be encouraged to drink eight 8-oz glasses of water over a 24-hour 
period, i.e., 64 oz. total.   
If Day 5 Cycle 1 steady state PK assessments are postponed to Day 5 of Cycle 2, the 
considerations described above will also be postponed to Day 5 of Cycle 2.   
On Day 5 of Cycle 1, patients in the Expansion Cohort will be required to stay at the clinical 
research unit for at least 12 hours for PK sampling and other assessments.  Patients will be 
required to return to the clinic on Day 6 of Cycle 1 for PK sample collection.  Patients will be 
encouraged to drink eight 8-oz glasses of water over a 24-hour period, i.e., 64 oz. total. 
5.4. 
Screen Failures 
Patients who fail inclusion and/or exclusion criteria may not be rescreened for the study. 


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6. 
TREATMENTS 
6.1. 
Investigational Product 
6.1.1. 
Description of Investigational Product 
CPX-POM prodrug, sodium ((6-cyclohexyl-4-methyl-2-oxopyridin-1(2H)-yl) oxy) methyl 
phosphate, is the phosphoryloxymethyl ester of CPX.  CPX-POM will be provided as a 
sterile liquid formulation for IV administration. 
6.1.2. 
Packaging and Labeling 
CPX-POM will be packaged in plastic, 10-mL vials containing CPX-POM 50 mg/mL 
solution.  Vials will be labeled according to applicable regulatory requirements.   
6.1.3. 
Storage and Handling 
CPX-POM vials must be stored under refrigerated conditions at 2 to 8 ºC.   
Only patients enrolled in the study may receive CPX-POM and only authorized site staff may 
supply or administer CPX-POM.  All CPX-POM must be stored in a secure, environmentally 
controlled, and monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. 
6.1.4. 
Dosage and Administration 
At baseline, the body surface area (BSA) will be calculated by the Dubois method using 
Screening (Visit 1) height and baseline (Visit 2) weight measurements.  The baseline BSA is 
to be used to determine the patient’s study drug dose.  Thereafter, BSA is to be recalculated 
on Day 1 of every other treatment cycle, starting with Cycle 3, and the patient’s study drug 
dose adjusted accordingly. 
Dubois Formula:  BSA= 0.007184 x W0.425 x H0.725 
The dose escalation procedure is described in Section 4, and further details and example 
doses are shown in Section 4.2. 
After completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, PK, and 
PD data to determine if any changes to the dosing schedule are indicated (e.g., adding an 
additional 5 days of dosing to each treatment cycle). 


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6.1.4.1. 
Dose Escalation Part of the Study 
CPX-POM will be administered as an IV infusion once daily on Days 1-5 of each 21-day 
treatment cycle.  CPX-POM will be added to a 100 mL piggyback bag of 0.9% sodium 
chloride solution and infused over a 10-minute period.  The initial dose for the first patient 
enrolled (i.e., Cohort 1) will be 30 mg/m2.   
6.1.4.2. 
Expansion Cohort 
CPX-POM will be administered as an IV infusion once daily on Days 1-5 of each 21-day 
treatment cycle.  CPX-POM will be added to a 100-mL piggyback bag of 0.9% sodium 
chloride solution and infused over a 20-minute period.  The dose administered will be 
900 mg/m2. 
6.1.5. 
Dose Modifications 
If a patient in the Dose Escalation part of the study develops a DLT, CPX-POM dosing 
should be discontinued until the toxicity is resolved (see definition of a DLT in Section 4).  If 
the toxicity resolves to at least Grade 1, treatment may be re-initiated and the dose of CPX-
POM should be reduced by one dose level.  If a patient has a second episode of the same 
DLT despite dose reduction, they should be permanently discontinued from study.  
Dose modifications are discouraged in the Expansion Cohort.  However, if a patient in the 
Expansion Cohort develops an SAE that the investigator believes may be mitigated by a dose 
modification, the Medical Monitor should be contacted to discuss the possibility of a dose 
modification.  
6.1.6. 
Compliance 
Administration of CPX-POM will be performed by site personnel.  Compliance will be 
assessed by inspection of drug accountability records at the study site.  
6.1.7. 
Accountability 
The investigator or designee (i.e., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused investigational medicinal product, placebos, and 
comparators.  This includes acknowledgment of receipt of each shipment of investigational 
product (quantity and condition), patient dispensing records, and returned or destroyed study 
product.  Dispensing records will document quantities received from CicloMed and 
quantities administered to patients, including lot number, date dispensed/administered, 
patient identifier number, and the initials of the person dispensing/administering the 
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At study initiation, the monitor will evaluate the site’s standard operating procedure for 
investigational medicinal product disposal/destruction in order to ensure that it complies with 
CicloMed requirements.  Drug may be returned or destroyed on an ongoing basis during the 
study, if appropriate.  At the end of the study, following final drug inventory reconciliation 
by the monitor, the study site will dispose of and/or destroy all unused investigational 
medicinal product supplies, including empty containers, according to these procedures.  If the 
site cannot meet CicloMed’s requirements for disposal, arrangements will be made between 
the site and CicloMed or its representative for destruction or return of unused investigational 
medicinal product supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by 
the study monitor over the course of the study.   
Further guidance and information for the final disposition of unused investigational product 
is provided in the Study Procedures Manual. 
6.2. 
Prior and Concomitant Medications 
Medications taken within 30 days before baseline (Study Visit 2) must be recorded as prior 
medications.   
Prohibited concomitant medications include any anti-cancer agents (with the exception of 
planned concomitant gemcitabine + cisplatin chemotherapy in patients enrolled in the 
expansion cohort), steroids (except stable doses being taken for brain metastases), any iron 
replacement therapy, warfarin, or any drug known to have significant nephrotoxicity.  A 
minimum of 10 days between termination of the prohibited concomitant medications or a 
duration of five elimination half-lives will be required prior to administration of IV 
CPX-POM to eligible patients.  Concomitant radiation therapy is also prohibited. 
Patients should not receive anti-emetic medications before and following Dose 1 of Cycle 1 
for each treatment cohort.  However, anti-emetics such as ondansetron or granisetron that 
have a mild QTc prolonging effect are allowed starting with Dose 2 of Cycle 1, if used with 
caution and attention to the approved labelling.   
The cisplatin + gemcitabine dosing regimen for chemotherapy-eligible patients enrolled in 
the expansion cohort will be administered per the institution’s standard of care. 
All concomitant medications will be recorded from the time of Screening through the 
Follow-up Period, with the exception that, for the Expansion Cohort, starting on the day of 
cystectomy, only medications associated with an AE related to CPX-POM treatment need to 
be recorded; routine medications and medications associated with the cystectomy procedure 
do not need to be recorded. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PATIENT DISCONTINUATION/WITHDRAWAL
  
7.1. 
Discontinuation of Study Treatment 
Treatment should be discontinued for a DLT until the toxicity is resolved.  If treatment is 
reinitiated, then the dose of CPX-POM should be reduced as described in Section 6.1.5.  If a 
patient has a second episode of the same DLT despite dose reduction, he or she should be 
removed from study as outlined in the Schedules of Assessments (Table 1, Table 2, and 
Table 3) (patients in the Dose Escalation Cohort should complete Day 22 and the Early 
Termination Visit and patients in the Expansion Cohort should complete the D42 Safety 
Assessments). 
In the event of discontinuation of CPX-POM, every effort should be made to complete the 
assessments that are scheduled for the Follow-up/Early Termination visit.  See the Schedules 
of Assessments (Table 1, Table 2, and Table 3) for data to be collected at the time of early 
termination. 
7.2. 
Patient Discontinuation/Withdrawal from the Study 
A patient may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons. 
If the patient withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a patient withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
If a patient withdraws prematurely from the trial for any reason, study staff should make 
every effort to complete the full set of evaluations scheduled for the Follow-up/Early 
Termination visit.  See the Schedules of Assessments (Table 1, Table 2, and Table 3) for data 
to be collected at the time of early termination. 
7.3. 
Lost to Follow Up 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a patient fails to return to the clinic for a required 
study visit: 


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• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
study. 
• Before a patient is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the patient (where possible, 3 telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods).  These contact attempts should be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  


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8. 
STUDY ASSESSMENTS 
8.1. 
Cancer Evaluation 
8.1.1. 
Dose Escalation Part of the Study 
All patients in the Dose Escalation Part will undergo a cancer evaluation to include 
determination of staging and metastases for screening purposes.  For the screening 
assessments, all sites of disease will be imaged by CT, if possible.  If the anatomic region 
cannot be adequately imaged by CT, magnetic resonance imaging (MRI) may be used 
instead.  Subsequent assessments should use the same radiographic methods as used during 
Screening.  Disease response will be assessed by the investigator using RECIST, version 1.1 
(Eisenhauer et al, 2009; see Appendix 1).   
For patients in the Dose Escalation Part of the study, disease response assessments will be 
performed for patients with measurable disease within 28 days prior to the first dose of 
CPX-POM and repeated before the first study drug dose (Day 1) of every second cycle (i.e., 
at approximately 6-week intervals).  If a patient with measurable disease discontinues from 
the study after 6 weeks and before a disease response assessment is scheduled, an additional 
assessment may be performed, upon consultation with the Sponsor, at the end of treatment 
(i.e., on approximately Day 22 of the last cycle).  Tumor markers applicable to the patient’s 
solid tumor type (e.g., prostate-specific antigen [PSA] for prostate cancer; cancer antigen-125 
[CA-125] in ovarian cancer; carcinoembryonic antigen [CEA] in colorectal or pancreatic 
cancer, cancer antigen 19-9 [CA-19-9] in pancreatic cancer) will also be measured within 
±2 days of tumor measurements. 
8.1.2. 
Expansion Cohort 
It is mandatory to obtain tumor tissue at baseline (archived tumor tissue from TURBT may 
be used) and at the time of RC.  Tumors will be assessed in a standard manner and given 
grade/stage according to the AJCC criteria.  Efficacy will be assessed based on pathologic 
criteria and evidence of pharmacologic activity in the target tissue.  Pathological 
downstaging will be considered as any tumor with <ypT2N0 disease. 
Long-term follow-up information may be obtained from the patient’s medical record or may 
be obtained by telephone call if information is not available from the medical records. 


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8.2. 
Safety Assessments 
8.2.1. 
Adverse Events and Serious Adverse Events 
8.2.1.1. 
Definitions 
Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
medicinal product and which does not necessarily have a causal relationship with this 
treatment.  An AE can therefore be any unfavorable and unintended sign, symptom, or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
AEs also include the following: 
• Pre- or post-treatment complications that occur as a result of protocol mandated
procedure (e.g. such as venipuncture, biopsy) during or after Screening (before the
administration of study investigational medicinal product).
• Any pre-existing condition that increases in severity, or changes in nature during or as
a consequence of the study investigational medicinal product phase of a human
clinical trial, will also be considered an AE.
• Complications and termination of pregnancy (see Section 8.2.2 for additional 
information)
• All AEs that occur from the study screening visit onwards and throughout the
duration of the study, including the follow-up off study medication period should be
recorded as an AE.
An AE does not include the following: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction,
transfusion) performed; the condition that leads to the procedure is an AE.
• Pre-existing diseases or conditions or laboratory abnormalities present or detected
before the screening visit that do not worsen.
• If progression of underlying malignancy is clearly consistent with the suspected
progression of the underlying cancer as defined by RECIST 1.1, or with clinical
symptoms (clinical progression), it should not be reported as an AE/SAE.  Similarly,
hospitalization due exclusively to the progression of underlying malignancy should
NOT be reported as an SAE.


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• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions).
• Any medical condition or clinically significant laboratory abnormality with an onset 
date before the consent form is signed and not related to a protocol-associated 
procedure is not an AE.  It is considered to be pre-existing and should be documented 
on the medical history CRF. 
• Uncomplicated pregnancy. 
• An induced elective abortion to terminate a pregnancy without medical reason. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs, symptoms, and/or clinical sequelae 
resulting from lack of efficacy may be reported as AE or SAE if they fulfill the 
definition of an AE or SAE.
Serious Adverse Event
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease). 
ASAE is defined as any untoward medial occurrence that, at any dose: 
• Results in death
• Is life-threatening.  The term 
'life-threatening
' in the definition of 
'serious
' refers to an 
event in which the patientwas at risk of death at the time of the event.It does not 
refer to an event, which hypothetically might have caused death, if it were more 
severe.
• Requires inpatient hospitalization or prolongation of existing hospitalization.  In 
general, hospitalization signifies that the patienthas been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  Ifa complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious.
When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.  Hospitalization for elective treatment of a pre-existing 
condition that did not worsen from baseline is not considered an AE. 
definition of an AE or SAE.
Serious Adverse Event
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions).
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease). 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
• An induced elective abortion to terminate a pregnancy without medical reason. 
• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs, symptoms, and/or clinical sequelae 
resulting from lack of efficacy may be reported as AE or SAE if they fulfill the 
• Requires inpatient hospitalization or prolongation of existing hospitalization.  In 
general, hospitalization signifies that the patienthas been detained (usually involving 
ASAE is defined as any untoward medial occurrence that, at any dose: 
• Results in death
• Is life-threatening.  The term 
'life-threatening
' in the definition of 
'serious
' refers to an 
event in which the patientwas at risk of death at the time of the event.It does not 
refer to an event, which hypothetically might have caused death, if it were more 
severe.
on the medical history CRF. 
• Uncomplicated pregnancy. 
• Any medical condition or clinically significant laboratory abnormality with an onset 
date before the consent form is signed and not related to a protocol-associated 
procedure is not an AE.  It is considered to be pre-existing and should be documented 


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• Results in persistent disability/incapacity.  The term disability means a substantial
disruption of a person’s ability to conduct normal life functions.  This definition is not
intended to include experiences of relatively minor medical significance such as
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma
(e.g., sprained ankle) which may interfere with or prevent everyday life functions but
do not constitute a substantial disruption.
• Is a congenital anomaly/birth defect in the offspring of a subject who received
investigational medicinal product.
• Other situations.  Medical or scientific judgment should be exercised in deciding
whether SAE reporting is appropriate in other situations such as important medical
events that may not be immediately life-threatening or result in death or
hospitalization but may jeopardize the patient or may require medical or surgical
intervention to prevent one of the other outcomes listed in the above definition. These
events should usually be considered serious.  Examples of important medical events
include invasive or malignant cancers, intensive treatment in an emergency room or
at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result
in hospitalization, or development of drug dependency or drug abuse.
8.2.1.2. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information  
All AEs and SAEs will be collected from the signing of the informed consent form (ICF) 
through the Follow-up visit (28 +/- 5 days after the last dose of study drug).  Note that for the 
Expansion Cohort, starting on the day of cystectomy, only AEs related to CPX-POM 
treatment need to be recorded; AEs related to the cystectomy procedure do not need to be 
recorded. 
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the CRF not the AE section. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a patient has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the Sponsor. 


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8.2.1.3. 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrences. 
8.2.1.4. 
Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification (within 24 hours from the first time a site team member is made aware of 
the event) by the investigator to the Sponsor of a SAE is essential so that legal obligations 
and ethical responsibilities towards the safety of patients and the safety of a study 
intervention under clinical investigation are met.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Boards (IRB), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then 
file it along with the Investigator’s Brochure and will notify the IRB, if appropriate according 
to local requirements. 
8.2.1.5. 
Reporting Procedures 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event.  The investigator will then record all relevant AE/SAE information in the 
CRF. 
It is not acceptable for the investigator to send photocopies of the patient’s medical records in 
lieu of completion of the AE/SAE CRF page.  There may be instances when copies of 
medical records for certain cases are requested by CicloMed or its designee.  In this case, all 
patient identifiers, with the exception of the patient number, will be redacted on the copies of 
the medical records before submission. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 


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All SAEs will be recorded and reported to the Sponsor or their designee within 24 hours from 
the time any site team member is made aware of the event.  The investigator will submit any 
updated SAE data to the Sponsor within 24 hours of it being available.  If any part of the 
source providing details of the event is not available, the Investigator will submit the SAE 
with as much information as he/she has at the time of the reporting requirements. 
Contacts and procedures for SAE reporting can be found in the Study Procedures Manual.  
8.2.1.6. 
Assessment of Causality 
The investigator is obligated to assess the relationship between CPX-POM and each 
occurrence of each AE/SAE as follows:  
• There is a "reasonable possibility" of a relationship between the CPX-POM and the AE.
This conveys that there are facts, evidence, and/or arguments to suggest a causal
relationship, rather than a relationship cannot be ruled out.
• There is not a “reasonable possibility” of a relationship between CPX-POM and the AE.
The investigator will use clinical judgment to determine the relationship.  Alternative causes, 
such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and 
investigated.  The investigator will also consult the Investigator’s Brochure (IB) in his/her 
assessment. 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor or contract research organization 
(CRO).  However, it is very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to the Sponsor or 
CRO.  The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.  
The relationship to study procedures (e.g., invasive procedures such as venepuncture or 
biopsy) should also be assessed using the following considerations: 
• There is a reasonable possibility that the AE occurred as a result of protocol-
mandated procedures such as venipuncture or biopsy.


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• There is not a reasonable possibility that the AE occurred as a result of a protocol-
mandated procedure.   
8.2.1.7. 
Assessment of Intensity 
The investigator will make an assessment of intensity (Grade) for each AE and SAE reported 
during the study, using as a guide the NCI CTCAE, as provided in the Study Procedures 
Manual.   
8.2.1.8. 
Follow-up of Adverse Events and Serious Adverse Events 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by CicloMed or its 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible.  This 
may include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
If a patient dies during participation in the study or during a recognized follow-up period, the 
investigator will provide CicloMed or its designee with a copy of any post-mortem findings 
including histopathology.   
New or updated information will be recorded in the originally completed CRF. 
The investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt 
of the information.  Contacts for SAE reporting can be found in the Study Procedures 
Manual. 
8.2.2. 
Pregnancy 
Pregnancies in female patients and female partners of male patients will be recorded from 
after the start of study intervention until 30 days after the last dose.  All pregnancies must be 
followed to conclusion to determine outcomes for both mother and baby.   
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE.  A spontaneous 
abortion is always considered to be an SAE and will be reported as such.  Any post-study 
pregnancy-related SAE considered reasonably related to the study intervention by the 
investigator will be reported to the Sponsor as described in Sections 8.2.1.4 and 8.2.1.5.  
While the investigator is not obligated to actively seek this information in former study 
patients, he or she may learn of an SAE through spontaneous reporting.  


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8.2.2.1. 
Male Patients with Partners who Become Pregnant 
The investigator will attempt to collect pregnancy information on any male patient’s female 
partner who becomes pregnant while the male patient is in this study.  This applies only to 
male patients who receive CPX-POM. 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy.  The female 
partner will also be followed to determine the outcome of the pregnancy.  Information on the 
status of the mother and child will be forwarded to the Sponsor.  Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date.  Any termination 
of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure.  
8.2.2.2. 
Female Patients who Become Pregnant 
The investigator will collect pregnancy information on any female patient who becomes 
pregnant while participating in this study.  Information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of a patient's pregnancy.  
The 
patient will be followed to determine the outcome of the pregnancy.  The investigator will 
collect follow-up information on the patient and the neonate and the information will be 
forwarded to the Sponsor.  Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date.  Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
Any female patient who becomes pregnant while participating in the study will discontinue 
CPX-POM and be withdrawn from the study.  
8.2.3. 
Other Safety and Screening Assessments 
8.2.3.1. 
Cardiac Evaluation 
Patients will undergo a cardiac evaluation at Screening using MUGA or ECHO to evaluate 
their eligibility to participate in the study. 
Patients will also undergo a chest X-ray or CT scan to confirm normal cardiac 
appearance/heart size at Screening.  
8.2.3.2. 
Eastern Cooperative Oncology Group 
Patients will be evaluated for ECOG performance status at Screening and Follow-Up to 
evaluate their eligibility to participate in the study.  The ECOG performance status grades 
and criteria are shown in Table 7. 


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Table 7. 
Eastern Cooperative Performance Status  
GRADE ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light housework, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 
5 
Dead 
*Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology
Group. Am J Clin Oncol. 1982;5:649-655.
8.2.3.3. 
Physical Examinations 
A complete physical examination will be conducted at Screening and Follow-up.  At each 
other study visit, patients will be assessed for continued dosing and any possible 
symptoms/toxicities and a physical examination may be performed, if indicated (see 
Schedules of Assessments, Table 1, Table 2, and Table 3).  Body weight should be measured 
at each study visit.  Height should be measured at Screening.  BSA will be calculated as 
described in Section 6.1.4.  
8.2.3.4. 
Vital Signs 
Vital signs will include blood pressure, respiratory rate, pulse, oxygen saturation, and 
temperature and will be measured at the times and days shown in the Schedules of 
Assessments (Table 1, Table 2, and Table 3).   
Vital signs will be measured before any blood draws or injections scheduled for the same 
time point.   


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8.2.3.5.
Electrocardiogramsand Holter Monitoring
At Screening, 12-lead ECGs will be performed in triplicate, with each measurement 
separated by 2 minutes.  The average of the 3 screening ECGs will be used to calculate QTc 
and QTcF (Fridericia’s formula): 
to determine study eligibility.  Thereafter, single 12-lead ECGs will be performed at the dates 
and times indicated in the Schedules of Assessments (Table 1, Table 2, and Table 3).   
On Day 1 of Cycle 1 for the Dose Escalation cohorts only, digital Holter monitoring will be 
performed from 45 minutes pre-dose through 24 hours post-dose in order to examine any 
potential QTc changes and relate those, if present, to simultaneously obtained blood samples 
for plasma drug and/or metabolite concentration determination.  ECG extractions of the 
continuous Holter recordings will be performed at 45, 30, and 15 minutes pre-dose and at 
specific post-dose time points coinciding with the serial blood sampling time points for PK.
Patients will be instructed to assume a supine position 5 to 10 minutes prior to each serial 
blood sampling time point and remain supine throughout the 5-minute ECG extraction period 
just prior to serial blood sample collection.  During the 24-hour Holter monitoring period, a 
12-lead ECG tracing may be printed out at any time while the patient is in the clinic at the 
discretion of the investigator.   
If for any reason Holter monitoring is not performed in conjunction with the PK sampling on 
Day 1or the tracings are of poor quality, Holter monitoring may be performed in conjunction 
with the PK sampling on Day 5.
8.2.3.6.
Clinical Laboratory Assessments
All protocol-required laboratory assessments, including hematology (including complete 
blood count), clinical chemistry (including comprehensive metabolic panel), thyroid panel, 
coagulation testing, and urinalysis must be conducted in accordance with the Study 
Procedures Manual and the Schedules of Assessments (Table 1,Table 2, and Table 3). 
Abnormal laboratory tests that are clinically significant should also be recorded as AEs on 
the CRF, or as medical history if noted during Screening. 
A listing of clinical laboratory tests to be performed is provided inTable 8.


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Table 8. 
Listing of Required Screening and Safety Laboratory Parameters 
Laboratory 
Assessments 
Parameters 
Hematology 
(CBC with 
differential) 
• Hemoglobin 
• Hematocrit  
• Platelet count 
• RBC count 
• Reticulocytes 
WBC Count with Differential 
• Neutrophils 
• Lymphocytes 
• Monocytes 
• Eosinophils 
• Basophils 
Clinical 
Chemistry 
(including CMP) 
• Potassium 
• Sodium 
• Chloride 
• Glucose  
• BUN 
• Creatinine  
• Creatinine 
clearance 
• ALP 
• ALT 
• AST 
• GGT 
• Alkaline 
phosphatase 
• Direct bilirubin 
• Indirect bilirubin 
• Total bilirubin 
• Total protein  
• Albumin 
• Calcium 
• Bicarbonate  
• Magnesium 
• Phosphate 
• Lipase 
• Amylase 
Coagulation  
• PT 
• aPTT 
 
Thyroid Panel  
• TSH 
• Free T4 
• Free and total T3 
Routine 
Urinalysis 
• Color 
• Turbidity 
• pH 
• Specific gravity 
• Glucose 
• Ketones 
• Nitrites 
• Bilirubin 
• Urobilirubin 
• Protein 
• RBCs 
• WBCs 
• Epithelial cells 
• Casts 
• Crystals 
• Bacteria 
• eGFR (Screening 
only) 
Other  
• Serum or urine 
hCG pregnancy 
test (for women of 
child bearing 
potential) 
• HIV (Screening 
only) 
• Hepatitis A 
(Screening only) 
• Hepatitis B 
(Screening only) 
• Hepatitis C 
(Screening only) 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial 
thromboplastin time; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete 
blood count; CMP = comprehensive metabolic panel; eGFR = estimated glomerular filtration rate; 
GGT = gamma glutamyltransferase; hCG = human chorionic gonadotropin; MCH = mean corpuscular 
hemoglobin;  
MCV = mean corpuscular volume; PT = prothrombin time; RBC = red blood cell; T3 = triiodothyronine;  
T4 = thyroxine; TSH = thyroid stimulating hormone; WBC = white blood cell. 


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8.2.3.7. 
Ophthalmologic Examinations 
Ophthalmologic examinations will be performed by a qualified ophthalmologist at Screening 
and Follow-up as indicated in the Schedule of Assessments (Table 1) for the Dose Escalation 
part of the study only.  Evaluations will include visual acuity, pupil exam, confrontation 
visual field, extraocular motility and alignment, interior slit lamp examination, and dilated 
fundus examination of the retina.  Additional ophthalmology evaluations may be requested at 
any other time, if indicated, as determined by the investigator. 
8.3. 
Pharmacokinetic Assessments 
Serial, 3-mL blood (plasma) samples will be taken for PK analysis of CPX-POM and 
metabolites at the times and days shown in the Schedules of Assessments (Table 1, Table 2, 
and Table 3).  Each PK sample should be collected as close as possible to the planned time.  
The actual date and time of each blood sample collection will be recorded.  PK samples may 
not be obtained from the same site where CPX-POM is infused.  
For the Expansion Cohort, on Day 1 of Cycle 1, single blood and clean-catch urine samples 
will be collected prior to the first CPX-POM infusion.  These pre-treatment samples will 
serve as patient baseline (or blank) samples to check for bioanalytical assay interference.   
Steady state PK will be evaluated based on plasma samples collected on Days 5-6 of Cycle 1 
of dosing, as shown in the Schedules of Assessments (Table 2 and Table 3).   
Urine samples for PK analysis of CPX-POM and metabolites and measurement of urine 
volume will be obtained from each patient in urine collection and storage containers.  
Samples will be collected during Cycle 1 only at the times and days shown in the Study 
Procedures Manual and the Schedules of Assessments (Table 1, Table 2, and Table 3).  Urine 
β-glucuronidase activity will be determined in the urine samples collected for PK analysis. 
The actual date and time of each sample collection, and the date and time of the previous 
dose of CPX-POM will be recorded.  Processing, storage, and shipping procedures are 
provided in the Study Procedures Manual. 
8.4. 
Pharmacodynamic Assessments 
8.4.1. 
Dose Escalation Part of the Study 
Serial 7-mL blood samples will be collected to characterize the pharmacologic effects of 
CPX-POM on circulating biomarkers of Wnt and Notch cell signaling pathways at the times 
and days shown in the Schedule of Assessments (Table 1).  Plasma and peripheral blood 
mononuclear cells (PBMCs) will be isolated from blood.  VEGF, IL-6, and IL-8 
concentrations will be measured in plasma by enzyme-linked immunoassay (ELISA).  


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Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) will be used to characterize 
gene expression of circulation biomarkers of Wnt and Notch signaling pathways in PBMCs. 
The actual date and time of each sample collection and the date and time of the previous dose 
of CPX-POM will be recorded.  Processing, storage, and shipping procedures are provided in 
the Study Procedures Manual. 
8.4.2. 
Expansion Cohort 
Formalin-fixed, paraffin-embedded bladder tumor tissues obtained prior to treatment by 
TURBT and at time of RC as indicated in the Schedule of Assessments (Table 2) and will be 
used to characterize the pharmacologic activity of CPX-POM employing the following 
assays:  
• Immunohistochemistry assays will be performed on prepared pathology slides to 
determine CPX-POM effects on cell proliferation by Ki67, Notch and Wnt signaling 
pathway activity, as well as CD8+ tumor-infiltrating lymphocytes (TIL). 
• RNA-seq will be performed on RNA extracted from paraffin-embedded tumor 
tissues, and if appropriate, followed by ChIPseq to identify cell signaling pathways 
and biomarkers up or down-regulated by CPX-POM treatment. 
Whether or not each patient is able to undergo RC will be recorded.  
Patients will be followed for recurrence and survival for up to 2 years post-enrollment.  If a 
patient experiences a recurrence within 2 years, they will continue to be followed for overall 
survival up to 2 years post-enrollment.  
 


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9. 
STATISTICAL
 CONSIDERATIONS 
The statistical analysis plan will be developed and finalized before database lock and will 
describe the finalized plans for analysis of study data.  This section is a summary of the 
planned statistical analyses at the time of protocol development. 
Safety, pharmacokinetic, and pharmacodynamic data will be presented separately for each 
part of the study (i.e., the Dose Escalation Part of the study and the Expansion Cohort). 
9.1. 
Number of Patients 
The maximum anticipated number of patients in the Single Patient and Standard Dose 
Escalation Cohorts will be approximately 24.  The estimated number of patients in the 
Expansion Cohort will be 12.  Thus, the total number of patients planned for enrollment in 
the study is 36.  
The actual number of patients enrolled will depend on the number of dose escalations and the 
need to further characterize individual cohorts.   
9.2. 
Analysis Sets 
9.2.1. 
Safety 
The Safety Set will consist of all patients who receive at least 1 dose of study drug.  All 
safety and PD data will be analyzed using the safety set.  
9.2.2. 
Pharmacokinetics 
The Pharmacokinetic Set will consist of all patients for whom a plasma and/or urine sample 
is obtained and analyzed for determination of plasma drug and metabolites concentration. 
9.3. 
Data Handling Conventions 
9.4. 
Demographic Data and Baseline Characteristics 
Demographic and baseline measurements will be summarized using standard descriptive 
methods. 
9.5. 
Safety Analysis 
Safety data will be presented in by-patient listings.  Categorical safety endpoints will be 
summarized by frequency of events/abnormalities for each dose group and overall.  
Continuous safety endpoints will be summarized using descriptive statistics (n, mean, 
standard deviation, median, Q1, Q3, minimum, maximum) for each dose group and overall. 


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9.5.1. 
Determination of Maximum Tolerated Dose 
The MTD is defined as the highest dose at which 1 or fewer of up to 6 patients experience a 
DLT.  The MTD will be exceeded if 2 or more patients in a cohort of up to 6 patients 
experience a DLT.  The number and proportion of patients who experience a DLT or Grade 2 
or higher AE will be listed and summarized by dose group.  A logistic regression will be used 
to estimate the predicted toxicity probability at each dose level.  Details will be provided in 
the statistical analysis plan.   
9.5.2. 
Extent of Exposure 
Patients’ extent of plasma and urine exposure to CPX-POM and metabolites will be 
summarized by dose group.   
9.5.3. 
Adverse Events 
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA).  System Organ Class (SOC), High-Level Group Term (HLGT), 
High-Level Term (HLT), Preferred Term, and Lower-Level Term (LLT) will be attached to 
the clinical database. 
AEs will be summarized on the basis of the date of onset for the event.  A treatment-
emergent AE will be defined as any AE that begins on or after the date of first dose of 
CPX-POM.  
Summaries (number and percentage of patients) of treatment-emergent AEs (by SOC, and 
Preferred Term) will be provided by dose group/cohort and overall. 
9.5.4. 
Laboratory Evaluations 
Summaries of clinical laboratory data will be provided using descriptive statistics.  No 
inferential statistics will be provided.  Quantitative values and change from baseline in 
quantitative values will be summarized by dose group.  Listings of all laboratory results and 
reference ranges will be provided.   
Graded laboratory abnormalities will be defined using the grading scheme based on CTCAE 
(4.03).  The incidence of treatment-emergent laboratory abnormalities, defined as values that 
increase at least one toxicity grade from baseline at any time post baseline up to and 
including the date of last dose of study drug, will be summarized by treatment group.  If 
baseline data are missing, then any graded abnormality (i.e., at least a Grade 1) will be 
considered treatment emergent. 


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9.5.5. 
Other Safety Evaluations 
Physical examination, ECG (including Holter Monitor), ophthalmologic examination, and 
vital signs data will be summarized by dose group and overall.  Concomitant medications 
will be coded using the World Health Organization Drug Dictionary and listed by dose 
group.   
9.6. 
Pharmacokinetic Analysis 
9.6.1. 
Pharmacokinetics in Plasma 
Plasma concentrations of CPX-POM and its metabolites will be determined by GLP-
validated liquid chromatography tandem mass spectroscopy(LC-MS/MS) assays.  Analysis 
of resultant plasma CPX-POM (and its metabolites) concentration-time data will be 
performed using non-parametric PK data analysis methods using Phoenix WinNonlin 7.0 
(Certara LP, Princeton, NJ).  PK parameters will be listed and summarized for each analyte 
using descriptive statistics (e.g., sample size, arithmetic mean, % coefficient of variation, 
standard deviation, median, minimum, and maximum).  The following PK parameters will be 
determined:   
• Cmax - Maximum observed plasma concentration (C
max) observed following 
administration of a single dose on Day 1 
• Tmax - Time to reach maximum observed plasma concentration (C
max) 
• AUC[0-t] - Area under the concentration-time curve following administration of a 
single dose on Day 1 
• AUC[t-∞] - Area under the concentration-time curve following administration of a 
single dose on Day 1 from the last quantifiable concentration (t) to infinity.  
• AUCinf - Area under the curve from time zero to extrapolated infinite time [AUC(0-∞)] 
following administration of a single dose on Day 1 as the sum of AUC[0-t] + AUC(t-∞) 
• Css
max- Maximum observed plasma concentration at steady-state on Day 5 
• Tss
max - Time to reach maximum observed plasma concentration (Css
max) on Day 5 
• AUCSS - Area under the concentration-time curve over the dosing interval at steady-
state following drug administration on Day 5 
• λ - Apparent first-order elimination rate constant 
• t½ - Apparent elimination half-life 
• Cls – Systemic clearance following administration of a single dose on Day 1 
• Clss – Systemic clearance at steady-state 
• Vd – Apparent volume of distribution 
• Vss
 – Steady-state volume of distribution 


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• Cmax Derived Accumulation Ratio - Css
max/C
max 
• AUC Derived Accumulation Ratio - AUCss/AUC
(0 - ∞) 
• CLr – Single dose (Day 1) and steady-state (Day 5) renal clearance  
Plasma drug and metabolite concentration-time data and derived plasma PK parameters will 
be presented in tabular and graphic format.  
For the Expansion Cohort, only steady state PK will be evaluated based on samples collected 
on Days 5-6 of Cycle 1 of dosing.  
9.6.2. 
Pharmacokinetics in Urine 
Urine concentrations of CPX-POM and its metabolites will be determined by GLP-validated 
LC-MS/MS assays.  Urine PK parameters will be generated using non-parametric PK data 
analysis methods, listed, and summarized for each analyte using descriptive statistics (e.g., 
sample size, arithmetic mean, % coefficient of variation, standard deviation, median, 
minimum, and maximum).  The following PK parameters will be determined:   
• Mass excreted 
• Excretion rate 
• Cumulative mass excreted 
Urine β–glucuronidase activity will be measured for each patient and summarized.  
For the Expansion Cohort, only steady state PK will be evaluated based on samples collected 
on Days 5-6 of Cycle 1 of dosing. 
9.6.3. 
Covariates and Pharmacokinetics 
The influence of dose, single versus multiple dose administration, β-glucuronidase activity, 
and other potential covariates (e.g., creatinine clearance, concomitant medications, 
concurrent disease) on CPX-POM and metabolite exposure will be examined in an 
exploratory fashion given the limited sample size. 
9.7. 
Pharmacodynamic Analyses 
9.7.1. 
Dose Escalation Part of the Study 
The pharmacologic effects of CPX-POM on circulating Wnt and Notch cell signaling 
biomarkers will be characterized in plasma and PBMCs in the Dose Escalation Part of the 
Study.  Plasma concentrations of VEGF, IL-6, and IL-8 will be determined prior to, during, 
and following CPX-POM treatment for each cycle by ELISA.  Expression of survivin; Notch 


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receptors 1, 2, and 3; Notch ligand Jagged-1, Notch target proteins HES1, Hey1, cyclin D1, 
and cMyc; as well as ϒ-Secretase proteins Presinilin-1 and Nicastrin, will be determined in 
PBMCs by qRT-PCR.   
Relationships between observed biomarker changes and drug and/or metabolite exposure as 
well as other measures will be explored using descriptive statistics, and/or additional PK/PD 
modeling to support the dose selection for future studies.  Demographic and baseline 
characteristics may be included in the modeling analysis.  
9.7.2. 
Expansion Cohort 
The complete (ypT0N0) and partial (<ypT2N0) pathologic response rates at the time of RC 
will be assessed locally at each clinical trial site and will be presented in a by-patient listing. 
By-patient listings of the results of bladder tumor tissues analyses by immunohistochemistry 
(Notch, Wnt, CD8+ lymphocyte infiltration, Ki67), RNA-seq, and ChIP-seq will be 
provided. 
Listings of the number of patients treated with CPX-POM who are unable to undergo RC 
will be provided.  
RFS at 2 years post-enrollment will be calculated.   
9.8. 
Interim Analyses 
No formal interim analysis is planned.  After each Dose Escalation cohort is completed, an 
SRC comprised of the CRO Medical Monitor, Principal Investigator(s), and Sponsor 
representatives will meet to discuss the data and decide upon the next dose escalation.  In 
addition, after completion of Cycle 1 for the first 4 to 6 patients, the SRC will review safety, 
PK, and PD data to determine if any changes to the dosing schedule are indicated. 


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10. 
REGULATORY
, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1. 
Regulatory and Ethical Considerations 
10.1.1. 
Institutional Review Board/Ethics Committee 
IRBs must be constituted according to the applicable state and federal requirements of each 
participating location including International Council on Harmonisation (ICH) Good Clinical 
Practice (GCP). 
It is the responsibility of each investigational site to submit the protocol, IB, patient ICF, 
patient recruitment materials (if applicable), and other documentation as required by the IRB 
to their IRB for review and approval.  A copy of the written approval must be provided to the 
sponsor or CRO.  The documentation should clearly mention the approval/favorable opinion 
of the protocol, the patient ICF, and patient recruitment materials (if applicable), including 
respective version dates.  The written approval and a list of the voting members, their titles or 
occupations, and their institutional affiliations must be obtained from the IRB(s) and 
provided to the sponsor or CRO prior to the release of clinical study supplies to the 
investigational site and commencement of the study.  If any member of the IRB has direct 
participation in this trial, written notification regarding his or her abstinence from voting 
must also be obtained. 
Sites must adhere to all requirements stipulated by their respective IRB.  This includes 
notification to the IRB regarding: protocol amendments, updates to the patient informed 
consent, recruitment materials intended for viewing by patients, IND safety reports, serious 
and unexpected AEs, reports and updates regarding the ongoing review of the trial at 
intervals specified by the respective IRB, and submission of final study reports and 
summaries to IRB. 
It is the responsibility of each investigational site to submit information to the appropriate 
IRB for annual review and annual re-approval. 
10.1.2. 
Ethical Conduct of the Study 
This study will be conducted according to the protocol, Code of Federal Regulations 
(21 CFR Parts 50, 54, 56, and 312), the Declaration of Helsinki, and ICH GCP.  Each 
investigator will conduct the trial according to applicable local or regional regulatory 
requirements. 


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10.1.3. 
Informed Consent 
Prior to any study procedures being performed, patients and the person conducting the 
consent discussion will be required to sign and date the IRB-approved ICF, and each patient 
will be given a copy.  In addition, this information should be recorded in the patient’s 
medical record (i.e., source document). 
The written consent document will embody the elements of informed consent as described in 
the Declaration of Helsinki, the Code of Federal Regulations (21 CFR Part 50.25), the ICH 
GCP guidelines, and in accordance with any local regulations.  The investigator is 
responsible for the preparation, content, and IRB approval of the informed consent.  The ICF 
must be approved by the site-designated IRB and be acceptable to the sponsor or CRO. 
The ICF must be written in a language fully comprehensible to the prospective patient.  The 
investigator or designee shall give the patient adequate opportunity to read the ICF before it 
is signed and dated.  Information should be given in both oral and written form whenever 
possible and in the manner deemed appropriate by the IRB.  Patients must be given ample 
opportunity to inquire about details of the study. 
10.1.4. 
Confidentiality 
The investigator must assure that patients’ anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties.  
Patients will be assigned a unique identifier by the sponsor.  Any patient records or datasets 
that are transferred to the sponsor will contain the identifier only; patient names or any 
information which would make the patient identifiable will not be transferred.   
NOTE:  The investigator must keep a screening log showing codes, names, and addresses for 
all patients screened and for all patients enrolled in the trial. 
The patient must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law.  The level of disclosure must also be 
explained to the patient.  
The patient must be informed that his/her medical records may be examined by clinical 
quality assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
The investigator agrees that all information received from CicloMed, including but not 
limited to the Investigator Brochure, this protocol, CRFs, the investigational new drug, and 
any other study information, remain the sole and exclusive property of CicloMed during the 
conduct of the study and thereafter.  This information is not to be disclosed to any third party 
(except employees or agents directly involved in the conduct of the study or as required by 


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law) without prior written consent from CicloMed.  The investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain. 
10.2. 
Study Oversight 
10.2.1. 
Data Quality Assurance 
All patient data relating to the study will be recorded in a printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data).  The investigator 
is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.  
10.2.2. 
Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected.  Source documents are filed at the investigator’s site. 
Data reported on the CRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained.  The investigator may 
need to request previous medical records or transfer records, depending on the study.  Also, 
current medical records must be available. 
Definitions of what constitutes source data can be found in the Study Procedures Manual. 
10.2.3. 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed on a 


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rolling basis upon database lock for each site individually or as the Sponsor determines.  
A study site is considered closed when all required documents, study supplies, and 
investigational product have been collected and/or destroyed, and a study-site closure visit 
has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but 
are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the sponsor
's procedures, or GCP guidelines 
• Inadequate recruitment of patients by the investigator 
• Discontinuation of further CPX-POM development 
10.2.4. 
Reporting of Results and Publications 
CicloMed will fulfill its commitment to publicly disclose the results of this study through 
posting the results on the www.clinicaltrials.gov web site.   
A clinical study report will be prepared and provided to the regulatory agency(ies).  
CicloMed will ensure that the report meets the standards set out in the ICH Guideline for 
Structure and Content of Clinical Study Reports (ICH E3).  Note that an abbreviated report 
may be prepared in certain cases. 
Any investigator will submit any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation.  The investigator will comply with CicloMed’s request to delete 
references to its confidential information (other than the study results) in any paper or 
presentation and agrees to withhold publication or presentation for an additional 60 days in 
order to obtain patent protection if deemed necessary. 
The results of this study may be published or presented at scientific meetings.  If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before 
submission.  This allows the sponsor to protect proprietary information and to provide 
comments.  
The sponsor will comply with the requirements for publication of study results.  In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data.  In this 
case, a coordinating investigator will be designated by mutual agreement. 


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Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
10.2.5. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified.  These 
documents should be classified into at least the following two categories: (1) investigator’s 
study file, and (2) patient clinical source documents. 
The investigator’s study file will contain the protocol/amendments, CRF and query forms, 
IRB, and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and 
correspondence. 
The required source data includes at least the following information for each patient: 
• patient identification (name, date of birth, gender); 
• documentation that patient meets eligibility criteria, i.e., history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion 
criteria); 
• participation in trial (including trial number); 
• trial discussed and date of informed consent; 
• dates of all visits; 
• documentation that protocol specific procedures were performed; 
• results of efficacy parameters, as required by the protocol; 
• start and end date (including dose regimen) of trial medication; 
• record of all AEs and other safety parameters (start and end date, and preferably 
including causality and intensity); 
• concomitant medication (including start and end date, dose if relevant; dose changes 
should be motivated); 
• date of trial completion and reason for early discontinuation, if applicable. 
All clinical study documents must be retained by the investigator until at least 2 years after 
the last approval of a marketing application in an ICH region (i.e., United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH 
region; or, if no application is filed or if the application is not approved for such indication, 
until 2 years after the investigation is discontinued and regulatory authorities have been 
notified. Investigators may be required to retain documents longer if required by applicable 


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regulatory requirements, by local regulations, or by an agreement with CicloMed.  The 
investigator must notify CicloMed before destroying any clinical study records. 
Should the investigator wish to assign the study records to another party or move them to 
another location, CicloMed must be notified in advance (i.e. in the case of a Principal 
Investigator moving to a new location, retiring, etc.).  If a study site is assigned to another 
investigator for archival oversight or if the files are to be moved, this change will be noted in 
a memo, the Sponsor will be contacted, and the IRB will be notified depending on the IRB 
requirements. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all 
of the documents, special arrangements must be made between the investigator and 
CicloMed to store these in sealed containers outside of the site so that they can be returned 
sealed to the investigator in case of a regulatory audit.  When source documents are required 
for the continued care of the patient, appropriate copies should be made for storage outside of 
the site. 
Biological samples at the conclusion of this study may be retained in storage by the sponsor 
for a period up to 2 years for purposes of this study. 
10.2.6. 
Case Report Forms 
For each patient enrolled, a CRF must be completed and signed by the Principal Investigator 
or sub-investigator (as appropriate) within a reasonable time period after data collection.  
This also applies to records for those patients who fail to complete the study (even during a 
screening period if a CRF was initiated).  If a patient withdraws from the study, the reason 
must be noted on the CRF.  If a patient is withdrawn from the study because of a 
treatment-limiting AE, thorough efforts should be made to clearly document the outcome. 
10.2.7. 
Inspections 
The investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from CicloMed or its representatives, to IRBs, 
or to regulatory authority or health authority inspectors. 
10.2.8. 
Protocol Compliance 
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
10.2.9. 
Study Discontinuation 
Both the sponsor and the investigator reserve the right to terminate the study at any time.  
Should this be necessary, both parties will arrange discontinuation procedures and notify the 


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appropriate regulatory authority(ies) and IRBs.  In terminating the study, CicloMed and the 
investigator will assure that adequate consideration is given to the protection of the patients’ 
interests. 


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11. 
REFERENCES 
Abrams BB, Hanel H. Hoehler T. Ciclopirox olamine: a hydroxypyridone antifungal agent. 
Clin Dermatol. 1991;9(4):471-477. 
Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer. 
Can Urol Assoc J. 2010;4(1):56-64. 
American Cancer Society. Cancer Facts & Figures 2019. Atlanta: American Cancer Society; 
2019.  
Bohn M, Kraemer KT. Dermatopharmacology of ciclopirox nail lacquer topical solution 8% 
in the treatment of onychomyosis. J Am Acad Dermatol. 2000;43(4):S57-S69. 
Botteman MF, Pashos CL, Radaelli A, Laskin B, Hauser R. The health economics of bladder 
cancer: A comprehensive review of the published literature. Pharmacoeconomics 
2003;21(18);1315-1330. 
Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, Pruthi R, Quale DZ, 
Ritch CR, Seigne JD, Skinner EC, Smith ND, McKiernan JM. Diagnosis and Treatment of 
Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline. J Urol. 2016;196(4):1021-
1029. 
Clement PMJ, Hanauske-Abel HM, Wolff EC, Kleinman HK, Park MH. The antifungal drug 
ciclopirox inhibits deoxyhpusine and proline hydroxylation, endothelial cell growth and 
angiogenesis in vitro. Int J Cancer. 2002;100:491-498.  
ClinicalTrials.gov web site. Available at: https://clinicaltrials.gov/. Accessed May 18, 2017.  
CPX-POM Investigator’s Brochure. CicloMed LLC. 2017. 
Dash A, Galsky M, Vickers AJ, Serio AM, Koppie TM, Dalbagni G, Bochner BH. Impact of 
renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with 
urothelial carcinoma of the bladder. Cancer. 2006;107(3):506-513.  
Dihazi H, Dihazi GH, Jahn O, Meyer S, Nolte J, Asif AR, Mueller GA, Engel W. 
Multipotent adult germline stem cells and embryonic stem cells functional proteomics 
revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell 
differentiation. J Proteome Res. 2011;10:1962-1973. 
Eberhard Y, McDermott SP, Wang X, Gronda M, Venugopal A, Wood TE, Hurren R, Datti 
A, Batey RA, Wrana J, Antholine WE, Dick JE, Schimmer AD. Chelation of intracellular 
iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and 
myeloma cells. Blood. 2009;114(14):3064-3073. 


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Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck 
S, Gwyther S, Mooney M, Rubinstein L, Shakar L, Dodd L, Kaplan R, Lacombe D, Verweij 
J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
Eur J Cancer. 2009;45:228-247.  
[FDA] Food and Drug Administration. Guidance for Industry – S9 Nonclinical Evaluation 
for Anticancer Pharmaceuticals. March 2010. Available at: 
https://www.fda.gov/downloads/Drugs/Guidances/ucm085389.pdf. Accessed September 18, 
2017.  
Gupta AK. Ciclopirox: an overview. Int J Dermatol. 2001;40(5):305-310. 
Gupta AK, Plott T. Ciclopirox: a broad-spectrum antifungal with antibacterial and anti-
inflammatory properties. Int J Dermatol. 2004; 43(Suppl 1):3-8.  
Gupta AK, Sauder DN, Shear NH. Antifungal agents: an overview. Part 1. J Am Acad 
Dermatol. 1994;30(5 Pt 1):677-698. 
Hanel H, Smith-Kurtz E, Pastowsky S. Therapy of seborrheic eczema with an antifungal 
agent with an antiphlogistic effect. Mycoses. 1991;34(Suppl 1):91-93. 
Heney NM. Natural history of superficial bladder cancer.  Prognostic features and long-term 
disease course. The Urologic Clinics of North America 1992;19(3):429-433. 
Kellner HM, Arnold C, Christ OE, Eckert HG, Herok J, Hornke I, Rupp W. Investigations on 
the pharmacokinetics and biotransformation of the antimycotic ciclopiroxolamine in animals 
and humans after topical and systemic application. Anzneim-Forsch/Drug Res. 1981; 31(II). 
No. 8a:1337-1353.  
Kwong W-L, Lok C-N, Tse C-W, Wong E L-M, Che C-M. Anti-cancer iron(ii) complexes of 
pentadentate n-donor ligands: cytotoxicity, transcriptomics analyses, and mechanisms of 
action. Chem Eur J. 2015;21:3062–3072. 
Le Tourneau C, Lee JJ, Siu LL. Dose escalation methods in phase 1 cancer clinical trials. 
JNCI. 2009;101(10):708-720.  
Millan-Rodriguez F, Chéchile-Toniolo G, Salvador-Bayarri J, Palou J, Algaba F, Vicente-
Rodriguez J. Primary superficial bladder cancer risk groups according to progression, 
mortality and recurrence. J Urol. 2000;164(3 Pt 1):680-684. 
Minden MD, Hogge DE, Weir SJ, Kasper J, Webster DA, Patton L, Jitkova Y, Hurren R, 
Gronda M, Goard CA, Rajewski LG, Haslam JL, Heppert KE, Schorno K, Chang H, 
Brandwein JM, Gupta V, Schuh AC, Trudel S, Yee KW, Reed GA, Schimmer AD. Oral 


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ciclopirox olamine displays biological activity in a phase 1 study in patients with advanced 
hematologic malignancies. Am J Hematol. 2014; 89(4):363-368.  
NCI SEER. Cancer Stat Facts: Bladder Cancer. In Reports on Cancer: Annual Report to the 
Nation. . 2018 January. Available at: https://seer.cancer.gov/statfacts/html/urinb.html. 
Accessed 23 July 2019. 
Oken M, Creech R, Tormey D, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 
1982;5:649-655. 
Peyton CC, Tang D, Reich RR, Azizi M, Chipollini J, Pow-Sang JM, Manley B, Spiess PE, 
Poch MA, Sexton WJ, Fishman M, Zhang J, Gilbert SM. Downstaging and survival 
outcomes associated with neoadjuvant chemotherapy regimens among patients treated with 
cystectomy for muscle-invasive bladder cancer. JAMA Oncol. 2018;4(11):1535-1542. 
Sakurai K, Sakeguchi T, Yamaguchi H, Iwata K. Mode of action of 6-cyclohexyl-1-hydroxy-
4-methyl-2(1H)-pyridone ethanolamine salt (Hoe296). Chemotherapy.1978;24(2):68-76. 
Sidarovich V, Adami V, Gatto P, Greco V, Tebaldi T, Tonini GP, Quattrone A. Translational 
downregulation of hsp90 expression by iron chelators in neuroblastoma cells. Mol 
Pharmacol. 2015;87(3):513-524. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer Journal for 
Clinicians. 2019;69(1):7-34.  
Song S, Christova T, Perusini S, Alizadeh S, Bao RY, Miller BW, Hurren R, Jitkova Y, 
Gronda M, Isaac M, Joseph B, Subramanian R, Aman A, Chan A, Hogge DE, Weir SJ, 
Kaspar J, Schimmer AD, Al-awar R, Wrana JL, Altisano L. WNT inhibitor screen reveals 
iron dependence of β-catenin signaling in cancers. Cancer Res. 2011;71:7628-7639.  
Szüts D, Krude T. Cell cycle arrest at the initiation step of human chromosomal DNA 
replication causes DNA damage. J Cell Sci. 2004;117(Pt 21):4897-4908.  


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12. 
APPENDIX 
Appendix 1. 
RECIST Criteria Guidance 
Time Point Response of Measurable Disease (Target Lesions) with or without  
Non-Measurable Disease (Non-Target Lesions) 
Target Lesion Response 
Non-Target 
Lesion Response 
New Lesions 
Overall Response 
CR 
 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or NE 
No 
PR 
SD 
Non-PD or NE 
No 
SD 
NE 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations:  CR = Complete Response, PR = Partial Response, SD = Stable Disease, PD = Progressive 
Disease, and NE = Not All Evaluated 
 
 
Time Point Response of Non-Measurable Disease Only (Non-Target Lesions) 
Non-Target Lesion Response 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/Non-PD 
No 
Non-CR/Con-PD 
NE 
No 
NE 
Unequivocal Progression 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations:  CR = Complete Response, PD = Progressive Disease, NE = Not All Evaluated 
Note:  Non-CR/Non-PD is preferred over “Stable Disease” for non-target disease since SD is increasingly 
used as endpoint for assessment of efficacy in some trials, so to assign this category when no lesions can be 
measured is not advised 
 
Note:  If a CR is truly met at a time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline, makes the disease PD at that time point since disease must have 
reappeared after CR. 
 
Source:  Eisenhauer et al, 2009 
 

SAP_001.pdf: 
Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 1 of 125 
 
 
 
SPONSOR: 
CicloMed 
PROTOCOL NUMBER: 
CPX-POM-001 
STATISTICAL ANALYSIS PLAN 
(TFL shells) 
Author: 
Version: 
Version 2.0 
Date: 
03Nov2021 


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Cover and signature pages 
 
Sponsor: 
CicloMed 
Protocol Number: 
CPX-POM-001 
Study Title: 
A Phase 1, First-in-Human, Safety, Dose Tolerance, Pharmacokinetics, 
and Pharmacodynamics Study of CPX-POM in Patients with Advanced 
Solid Tumors 
Document Version No 
Version 2.0 
 
We, the undersigned, confirm that we have read, understood and agree to the content of this document 
and hereby authorize its approval. 
 
Name and Date are not required if electronic signatures are used. Do not resize boxes. 
 
Name 
Title 
[text box when using 
eSignatures]: 
Date 
Signature 
 
Principal 
Biostatistician II 


Sponsor: CicloMed 
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Name and Date are not required if electronic signatures are used. Do not resize boxes. 
 
Name 
Title 
[text box when using 
eSignatures]: 
Date 
Signature 
Medical Advisor 
 
Name and Date are not required if electronic signatures are used. Do not resize boxes. 
 
Name 
Title 
[text box when using 
eSignatures]: 
Date 
Signature 
Chief Scientific 
Officer 
CicloMed LLC 


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Table of Contents 
Cover and signature pages ............................................................................................................................................... 2 
Table of Contents ............................................................................................................................................................. 4 
Tables 14.1 ....................................................................................................................................................................... 9 
Table 14.1-1.1 - Patients disposition (All Patients Enrolled) - Dose Escalation ................................................................. 9 
Table 14.1-1.2 - Patients disposition (All Patients Enrolled) – Expansion ....................................................................... 11 
Table 14.1-2.1 - Number (%) of Patients in the Analysis Populations (All Patients Enrolled) - Dose Escalation ............. 14 
Table 14.1-2.2 - Number (%) of Patients in the Analysis Populations (All Patients Enrolled) - Expansion ...................... 15 
Table 14.1-3.1 - Summary of Demographic and Baseline Characteristics (Safety Population) - Dose Escalation ........... 16 
Table 14.1-3.2 - Summary of Demographic and Baseline Characteristics (Safety Population) - Expansion .................... 20 
Table 14.1-4.1 - Important Protocol Deviations (Safety Population) - Dose Escalation .................................................. 21 
Table 14.1-4.2 - Important Protocol Deviations (Safety Population) - Expansion .......................................................... 21 
Table 14.1-5.1.1 - Disease Characteristics (Safety Population) - Dose Escalation ........................................................... 22 
Table 14.1-5.1.2 - Disease Characteristics (Safety Population) - Expansion ................................................................... 26 
Table 14.1-5.2.1 - Other Medical History (Safety Population) - Dose Escalation ............................................................ 27 
Table 14.1-5.2.2 - Other Medical History (Safety Population) - Expansion .................................................................... 28 
Table 14.1-5.3.1 - Concomitant Diseases (Safety Population) - Dose Escalation ............................................................ 28 
Table 14.1-5.3.2 - Concomitant Diseases (Safety Population) - Expansion..................................................................... 28 
Table 14.1-6.1.1 - Prior Medications by Therapeutic Class and Preferred Term (Safety Population) - Dose 
Escalation ....................................................................................................................................................................... 29 
Table 14.1-6.1.2 - Prior Medications by Therapeutic Class and Preferred Term (Safety Population) - Expansion ......... 30 
Table 14.1-6.2.1 - Concomitant Medications by Therapeutic Class and Preferred Term (Safety Population) - Dose 
Escalation ....................................................................................................................................................................... 30 
Table 14.1-6.2.2 - Concomitant Medications by Therapeutic Class and Preferred Term (Safety Population) - 
Expansion ....................................................................................................................................................................... 30 
Table 14.1-7.1 - Overall Exposure to Study Drug and Drug Compliance (Safety Population) - Dose Escalation ............. 31 
Table 14.1-7.2 - Overall Exposure to Study Drug and Drug Compliance (Safety Population) - Expansion ...................... 32 
Tables 14.2 ..................................................................................................................................................................... 33 
Table 14.2-1.1 - Patients who have had at least one other post-baseline tumor assessment (Efficacy Population) - 
Dose Escalation .............................................................................................................................................................. 33 
Table 14.2-2.1 - Summary of Patients Responses (Efficacy Population) - Dose Escalation ............................................. 34 
Table 14.2-3.2 - Recurrence-Free Survival (RFS) (Efficacy Population) - Expansion ........................................................ 36 
Table 14.2-4.2 - Overall Survival (OS) (Efficacy Population) - Expansion ........................................................................ 37 
Table 14.2-5.2 - Patients who Undergo Radical Cystectomy (Efficacy Population) - Expansion ..................................... 38 
Tables 14.3 ..................................................................................................................................................................... 39 
Table 14.3-1.0 - Dose-Limiting Toxicity (DLT) (Safety Population) - Dose Escalation ...................................................... 39 
Table 14.3-1.1.1 - Overview of Adverse Events (Safety Population) - Dose Escalation .................................................. 40 


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Table 14.3-1.1.2 - Overview of Adverse Events (Safety Population) - Expansion ........................................................... 41 
Table 14.3-1.2.1 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) - Dose Escalation .................................................................................................. 42 
Table 14.3-1.2.2 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) - Expansion ........................................................................................................... 43 
Table 14.3-1.3.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) - Dose Escalation ........................................................................................... 43 
Table 14.3-1.3.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) - Expansion .................................................................................................... 43 
Table 14.3-1.4.1 - Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) - Dose Escalation ........................................................................................... 44 
Table 14.3-1.4.2 - Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) - Expansion .................................................................................................... 44 
Table 14.3-1.5.1 - Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System 
Organ Class and Preferred Term (Safety Population) - Dose Escalation ....................................................................... 44 
Table 14.3-1.5.2 - Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System 
Organ Class and Preferred Term (Safety Population) - Expansion ................................................................................ 45 
Table 14.3-1.6.1 - Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by 
System Organ Class and Preferred Term (Safety Population) - Dose Escalation ........................................................... 45 
Table 14.3-1.6.2 - Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by 
System Organ Class and Preferred Term (Safety Population) - Expansion .................................................................... 45 
Table 14.3-1.7.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety Population) - Dose Escalation ............................ 46 
Table 14.3-1.7.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety Population) - Expansion..................................... 46 
Table 14.3-1.8.1 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term and Maximal Severity (Safety Population) - Dose Escalation .............................................................. 47 
Table 14.3-1.8.2 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term and Maximal Severity (Safety Population) - Expansion ....................................................................... 48 
Table 14.3-1.9.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity (Safety Population) - Dose Escalation ............................................................ 48 
Table 14.3-1.9.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity (Safety Population) - Expansion ...................................................................... 48 
Table 14.3-2.1.1.1 - Summary of Hematology Laboratory Data (Safety Population) - Dose Escalation ......................... 49 
Table 14.3-2.1.1.2 - Summary of Hematology Laboratory Data (Safety Population) - Expansion .................................. 50 
Table 14.3-2.1.2.1 - Outside of Normal Range - Shift Table for Hematology Laboratory Parameters (Safety 
Population) - Dose Escalation ........................................................................................................................................ 51 
Table 14.3-2.1.2.2 - Outside of Normal Range - Shift Table for Hematology Laboratory Parameters (Safety 
Population) - Expansion ................................................................................................................................................. 52 
Table 14.3-2.1.3.1 - On-treatment Hematology Adverse Events: Worst NCI-CTCAE Grade per patient (Safety 
Population) - Dose Escalation ........................................................................................................................................ 53 
Table 14.3-2.1.3.2 - On-treatment Hematology Adverse Events: Worst NCI-CTCAE Grade per patient (Safety 
Population) - Expansion ................................................................................................................................................. 54 


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Table 14.3-2.1.4.1 - Shift table of Worst NCI-CTCAE Grade for Hematological parameters (Safety Population) - Dose 
Escalation ....................................................................................................................................................................... 55 
Table 14.3-2.1.4.2 - Shift table of Worst NCI-CTCAE Grade for Hematological parameters (Safety Population) - 
Expansion ....................................................................................................................................................................... 56 
Table 14.3-2.2.1.1 - Summary of Clinical Chemistry Laboratory Data (Safety Population) - Dose Escalation ................ 57 
Table 14.3-2.2.1.2 - Summary of Clinical Chemistry Laboratory Data (Safety Population) - Expansion ......................... 57 
Table 14.3-2.2.2.1 - Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters (Safety 
Population) - Dose Escalation ........................................................................................................................................ 57 
Table 14.3-2.2.2.2 - Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters (Safety 
Population) - Expansion ................................................................................................................................................. 58 
Table 14.3-2.2.3.1 - On-treatment Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient (Safety 
Population) - Dose Escalation ........................................................................................................................................ 58 
Table 14.3-2.2.3.2 - On-treatment Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient (Safety 
Population) - Expansion ................................................................................................................................................. 58 
Table 14.3-2.2.4.1 - Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters (Safety 
Population) - Dose Escalation ........................................................................................................................................ 59 
Table 14.3-2.2.4.2 - Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters (Safety 
Population) - Expansion ................................................................................................................................................. 59 
Table 14.3-2.3.1.1 - Summary of Coagulation Laboratory Data (Safety Population) - Dose Escalation ......................... 60 
Table 14.3-2.3.1.2 - Summary of Coagulation Laboratory Data (Safety Population) - Expansion .................................. 60 
Table 14.3-2.3.2.1 - Outside of Normal Range - Shift Table for Coagulation Laboratory Parameters (Safety 
Population) - Dose Escalation ........................................................................................................................................ 60 
Table 14.3-2.3.2.2 - Outside of Normal Range - Shift Table for Coagulation Laboratory Parameters (Safety 
Population) - Expansion ................................................................................................................................................. 61 
Table 14.3-2.4.1.1 - Summary of Thyroid Panel Laboratory Data (Safety Population) - Dose Escalation ...................... 62 
Table 14.3-2.4.1.2 - Summary of Thyroid Panel Laboratory Data (Safety Population) - Expansion ............................... 62 
Table 14.3-2.4.2.1 - Outside of Normal Range - Shift Table for Thyroid Panel Laboratory Parameters (Safety 
Population) - Dose Escalation ........................................................................................................................................ 62 
Table 14.3-2.4.2.2 - Outside of Normal Range - Shift Table for Thyroid Panel Laboratory Parameters (Safety 
Population) - Expansion ................................................................................................................................................. 63 
Table 14.3-2.5.1 - Summary of Other Laboratory Data (Safety Population) - Dose Escalation ...................................... 64 
Table 14.3-2.5.2 - Summary of Other Laboratory Data (Safety Population) - Expansion ............................................... 65 
Table 14.3-3.1.1 - Summary of Vital Signs (Safety Population) - Dose Escalation.......................................................... 66 
Table 14.3-3.1.2 - Summary of Vital Signs (Safety Population) - Expansion .................................................................. 66 
Table 14.3-3.2.1 - Summary of Abnormal Vital Signs (Safety Population) - Dose Escalation .......................................... 67 
Table 14.3-3.2.2 - Summary of Abnormal Vital Signs (Safety Population) - Expansion ................................................... 70 
Table 14.3-4.1.1 - Summary of ECG Parameters (Safety Population) - Dose Escalation ................................................. 71 
Table 14.3-4.1.2 - Summary of ECG Parameters (Safety Population) - Expansion .......................................................... 71 
Table 14.3-4.2.1 - Summary of Abnormal ECG Intervals (Safety Population) - Dose Escalation ..................................... 72 
Table 14.3-4.2.2 - Summary of Abnormal ECG Intervals (Safety Population) - Expansion .............................................. 74 
Table 14.3-4.3.1 - Shift Table for ECG Overall Interpretation (Safety Population) - Dose Escalation ............................. 75 


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Table 14.3-4.3.1 - Shift Table for ECG Overall Interpretation (Safety Population) - Expansion ...................................... 76 
Figures............................................................................................................................................................................ 77 
Figure 14.2-4.2 - Recurrence-Free Survival (RFS) (Efficacy Population) – Expansion ...................................................... 77 
Figure 14.2-5.2 - Overall Survival (OS) (Efficacy Population) - Expansion ....................................................................... 78 
Listings ........................................................................................................................................................................... 79 
Listing 16.2.1-1.1.1 - Preface to Inclusion and Exclusion Criteria - Dose Escalation ....................................................... 79 
Listing 16.2.1-1.1.2 - Preface to Inclusion and Exclusion Criteria - Expansion ................................................................ 80 
Listing 16.2.1-1.2.1 - List of Failed Inclusion and Exclusion Criteria (All Patients) - Dose Escalation .............................. 81 
Listing 16.2.1-1.2.2 - List of Failed Inclusion and Exclusion Criteria (All Patients) - Expansion ....................................... 81 
Listing 16.2.1-2.1 - Patient Disposition (Safety Population) - Dose Escalation ............................................................... 82 
Listing 16.2.1-2.2 - Patient Disposition (Safety Population) - Expansion ........................................................................ 83 
Listing 16.2.2.1 - Protocol Deviations (Safety Population) - Dose Escalation .................................................................. 84 
Listing 16.2.2.2 - Protocol Deviations (Safety Population) - Expansion .......................................................................... 84 
Listing 16.2.3.1 - Analysis Populations (Safety Population) - Dose Escalation ................................................................ 85 
Listing 16.2.3.2 - Analysis Populations (Safety Population) - Expansion ......................................................................... 85 
Listing 16.2.4-1.1 - Demographic and Baseline Characteristics (Safety Population) - Dose Escalation ........................... 86 
Listing 16.2.4-1.2 - Demographic and Baseline Characteristics (Safety Population) - Expansion ................................... 87 
Listing 16.2.4-2.1 - Pregnancy Test Results (Safety Population) - Dose Escalation ......................................................... 88 
Listing 16.2.4-2.2 - Pregnancy Test Results (Safety Population) - Expansion .................................................................. 88 
Listing 16.2.4-3.1 - Cancer History (Safety Population) - Dose Escalation ...................................................................... 89 
Listing 16.2.4-4.1 - Prior Cancer Therapies (Safety Population) - Dose Escalation ......................................................... 90 
Listing 16.2.4-5.1 - Medical History and Concomitant Disease (Safety Population) - Dose Escalation ........................... 91 
Listing 16.2.4-5.2 - Medical History and Concomitant Disease (Safety Population) - Expansion .................................... 92 
Listing 16.2.4-6.1 - Cardiac Function (Safety Population) - Dose Escalation ................................................................... 93 
Listing 16.2.4-6.2 - Cardiac Function (Safety Population) - Expansion ............................................................................ 93 
Listing 16.2.4-7.1 - Ophthalmologic Exam (Safety Population) - Dose Escalation ........................................................... 94 
Listing 16.2.4-8.1.1 - Prior and Concomitant Medications (Safety Population) - Dose Escalation .................................. 95 
Listing 16.2.4-8.1.2 - Prior and Concomitant Medications (Safety Population) - Expansion ........................................... 96 
Listing 16.2.4-8.2.2 - Chemotherapy (Safety Population) - Expansion ............................................................................ 97 
Listing 16.2.4-9.1 - Surgeries and Procedures (Safety Population) - Dose Escalation ..................................................... 98 
Listing 16.2.4-9.2 - Surgeries and Procedures (Safety Population) - Expansion .............................................................. 99 
Listing 16.2.5-1.1 - Treatment Administration (Safety Population) - Dose Escalation ................................................. 100 
Listing 16.2.5-1.2 - Treatment Administration (Safety Population) - Expansion .......................................................... 101 
Listing 16.2.5-2.1 - Infusion Interruption (Safety Population)- Dose Escalation .......................................................... 102 
Listing 16.2.5-2.2 - Infusion Interruption (All Patients Enrolled) - Expansion .............................................................. 102 
Listing 16.2.5-3.1 - Drug Exposure (Safety Population) - Dose Escalation .................................................................... 103 
Listing 16.2.5-3.2 - Drug Exposure (Safety Population) - Expansion ............................................................................. 103 


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Listing 16.2.6-1.1 - RECIST Target Lesions (Efficacy Population) - Dose Escalation ....................................................... 104 
Listing 16.2.6-2.1 - RECIST Non-Target Lesions (Efficacy Population) - Dose Escalation ............................................... 105 
Listing 16.2.6-3.1 - RECIST response (Efficacy Population) - Dose Escalation ............................................................... 106 
Listing 16.2.6-4.1 - Tumor Marker (Efficacy Population) - Dose Escalation .................................................................. 107 
Listing 16.2.6-5.2 - Evaluable TURBT Results (Efficacy Population) - Expansion ........................................................... 108 
Listing 16.2.6-6.2 - Radical Cystectomy (Efficacy Population) - Expansion ................................................................... 109 
Listing 16.2.6-7.2 - Determination of Recurrence and Survival (Efficacy Population) - Expansion ............................... 110 
Listing 16.2.6-8.2 - Recurrence-Free Survival and Overall Survival (Efficacy Population) - Expansion .......................... 111 
Listing 16.2.7-1.1 - Dose-Limiting Toxicity (Safety Population) - Dose Escalation......................................................... 112 
Listing 16.2.7-2.1 - Adverse Events (Safety Population) - Dose Escalation ................................................................... 113 
Listing 16.2.7-2.2 - Adverse Events (Safety Population) - Expansion ............................................................................ 113 
Listing 16.2.7-3.1 - Serious Adverse Events (Safety Population) - Dose Escalation ....................................................... 113 
Listing 16.2.7-3.2 - Serious Adverse Events (Safety Population) - Expansion ............................................................... 114 
Listing 16.2.7-4.1 - Adverse Events Leading to Discontinuation (Safety Population) - Dose Escalation ........................ 114 
Listing 16.2.7-4.2 - Adverse Events Leading to Discontinuation (Safety Population) - Expansion ................................ 114 
Listing 16.2.7-5.1 - Adverse Events Leading to Death (Safety Population) - Dose Escalation ....................................... 115 
Listing 16.2.7-5.2 - Adverse Events Leading to Death (Safety Population) - Expansion ................................................ 115 
Listing 16.2.8-1.1 - Patients Laboratory Profile: Hematology (Safety Population) - Dose Escalation ............................ 116 
Listing 16.2.8-1.2 - Patients Laboratory Profile: Hematology (Safety Population) - Expansion .................................... 117 
Listing 16.2.8-2.1 - Patients Laboratory Profile: Clinical Chemistry (Safety Population) - Dose Escalation ................... 117 
Listing 16.2.8-2.2 - Patients Laboratory Profile: Clinical Chemistry (Safety Population) - Expansion ........................... 117 
Listing 16.2.8-3.1 - Patients Laboratory Profile: Coagulation (Safety Population) - Dose Escalation ............................ 118 
Listing 16.2.8-3.2 - Patients Laboratory Profile: Coagulation (Safety Population) - Expansion ..................................... 118 
Listing 16.2.8-4.1 - Patients Laboratory Profile: Thyroid Panel (Safety Population) - Dose Escalation ......................... 118 
Listing 16.2.8-4.2 - Patients Laboratory Profile: Thyroid Panel (Safety Population) - Expansion .................................. 119 
Listing 16.2.8-5.1 - Patients Laboratory Profile: Urinalysis (Safety Population) - Dose Escalation ................................ 120 
Listing 16.2.8-5.2 - Patients Laboratory Profile: Urinalysis (Safety Population) - Expansion ........................................ 120 
Listing 16.2.9-1.1 - Vital Signs (Safety Population) - Dose Escalation ........................................................................... 121 
Listing 16.2.9-1.2 - Vital Signs (Safety Population) - Expansion .................................................................................... 122 
Listing 16.2.9-2.1 - ECG Results (Safety Population) - Dose Escalation ......................................................................... 123 
Listing 16.2.9-2.2 - ECG Results (Safety Population) - Expansion.................................................................................. 124 
Listing 16.2.9-3.1 - Digital Holter Monitoring (Safety Population) - Dose Escalation .................................................... 125 


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Tables 14.1 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
 
Table 14.1-1.1 - Patients disposition 
(All Patients Enrolled) - Dose Escalation 
Page 1 of Y 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 [D6] mg/m^2 [D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Cycle 1 [n (%)] 
Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed the cycle [a] [c] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Cycle 2 [n (%)] 
Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed the cycle [b] [c] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
<repeat until last cycle> 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 10 (if Cycle 1 was not the last cycle). 
[b] A patient completed Cycle 2 (or any next cycle) if s/he attended visit Day 6 (if Cycle 2 or any next cycle was not the last 
cycle). 
[c] A patient completed the Last Cycle if s/he attended the last visit of the cycle (visit Day 10 for Cycle 1 or visit Day 6 for 
Cycle 2 or any next cycle) and if s/he attended the final visit at least 22 days after the first dose in the last cycle. 
[d] Calculated as [(Date of end of study – Date of first dose) + 1]/30.4375. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
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--- DELIVERY TYPE ---- 
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Extract date: DDMMMYYYY 
Page 1 of Y 
Table 14.1-1.1 - Patients disposition 
Page 10 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
(All Patients Enrolled) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 [D6] mg/m^2 [D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Reason for end of study [n (%)] 
Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Dose Limitimg Toxicity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Pregnancy 
Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Attended the follow-up visit (Day 
28) [n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Time on study (Months) [d] 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 10 (if Cycle 1 was not the last cycle). 
[b] A patient completed Cycle 2 (or any next cycle) if s/he attended visit Day 6 (if Cycle 2 or any next cycle was not the last 
cycle). 
[c] A patient completed the Last Cycle if s/he attended the last visit of the cycle (visit Day 10 for Cycle 1 or visit Day 6 for 
Cycle 2 or any next cycle) and if s/he attended the final visit at least 22 days after the first dose in the last cycle. 
[d] Calculated as [(Date of end of study – Date of first dose) + 1]/30.4375. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


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Protocol: CPX-POM-001 
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Page 11 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
 
Table 14.1-1.2 - Patients disposition 
(All Patients Enrolled) – Expansion 
Page 1 of Y 
 
 
 
 
 
Cycle 1 [n (%)]) 
Cisplatin 
ineligible 
N=X 
Chemotherapy 
eligible 
N=X 
Overall 
N=X 
 
Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed the cycle [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Cycle 2 [n (%)]) 
Treated 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed the cycle [b] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Cycle 3 [n (%)] [d] 
XX (XX.X) 
XX (XX.X) 
Treated 
XX (XX.X) 
XX (XX.X) 
Completed the cycle [c] 
XX (XX.X) 
XX (XX.X) 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 6. 
[b] A patient completed Cycle 2 if s/he attended visit Day 26. 
[c] A patient completed Cycle 3 if s/he attended visit Day 48. 
[d] Applicable to Chemotherapy eligible group only. 
[e] A patient completed the study if s/he completed 2 cycles (cisplatin-ineligible patients) or 3 cycles (chemotherapy eligible 
patients) and had radical cystectomy. 
[f] Calculated as [(Date of end of study – Date of first dose) + 1]/30.4375. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 12 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
 
Table 14.1-1.2 - Patients disposition 
(All Patients Enrolled) - Expansion 
Page 1 of Y 
 
 
Cisplatin 
ineligible 
N=X 
Chemotherapy 
eligible 
N=X 
Overall 
N=X 
Completed end of treatment 
[n (%)] 
visit (Day 42 or Day 64) XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Discontinued from treatment [n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Reason for discontinuation 
(%)] 
from the treatment [n 
Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Dose Limitimg Toxicity 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Pregnancy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Adverse Event 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Undergone 
(%)] 
radical cystectomy (Day 56 or Day 78) [n XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed the study [e] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Completed at least one follow-up visit [n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 6. 
[b] A patient completed Cycle 2 if s/he attended visit Day 26. 
[c] A patient completed Cycle 3 if s/he attended visit Day 48. 
[d] Applicable to Chemotherapy eligible group only. 
[e] A patient completed the study if s/he completed 2 cycles (cisplatin-ineligible patients) or 3 cycles (chemotherapy eligible 
patients) and had radical cystectomy. 
[f] Calculated as [(Date of end of study – Date of first dose) + 1]/30.4375. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 13 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
 
Table 14.1-1.2 - Patients disposition 
(All Patients Enrolled) - Expansion 
Page 1 of Y 
 
 
Cisplatin 
ineligible 
N=X 
Chemotherapy 
eligible 
N=X 
Overall 
N=X 
 
 
Reason for end of study [n (%)] 
Death 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Lost to Follow-up 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Physician Decision 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Withdrawn Consent 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Time on study (Months) [f] 
n 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
 
Percentages are based on the number of patients enrolled. 
[a] A patient completed Cycle 1 if s/he attended visit Day 6. 
[b] A patient completed Cycle 2 if s/he attended visit Day 26. 
[c] A patient completed Cycle 3 if s/he attended visit Day 48. 
[d] Applicable to Chemotherapy eligible group only. 
[e] A patient completed the study if s/he completed 2 cycles (cisplatin-ineligible patients) or 3 cycles (chemotherapy eligible 
patients) and had radical cystectomy. 
[f] Calculated as [(Date of end of study – Date of first dose) + 1]/30.4375. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
Table 14.1-2.1 - Number (%) of Patients in the Analysis Populations 
Page 14 of 125 
 
 
PROGRAMMING NOTES: 
• 
For the safety population, patients are displayed based on the actually received treatment. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
(All Patients Enrolled) - Dose Escalation 
 
CPX-POM 30 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
mg/m^2 
[D2] mg/m^2 [D3] mg/m^2 
[D4] mg/m^2 [D5] mg/m^2 [D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Safety Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Efficacy Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Percentages are based on the number of enrolled patients. 
The Safety population includes all patients who have received at least one dose of CPX-POM. 
The Efficacy population includes all patients who have received at least one dose of CPX-POM, had RECIST measurable disease at 
baseline and had at least one other post-baseline tumor assessment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 15 of 125 
 
 
PROGRAMMING NOTES: 
• 
For the safety population, patients are displayed based on the actually received treatment. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
Table 14.1-2.2 - Number (%) of Patients in the Analysis Populations 
(All Patients Enrolled) - Expansion 
 
Cisplatin 
ineligible 
Chemotherapy 
eligible 
Overall 
N=X 
N=X 
N=X 
n (%) 
n (%) 
n (%) 
Safety Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Efficacy Population 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
Percentages are based on the number of enrolled patients. 
The Safety population includes all patients who have received at least one dose of CPX-POM. 
The Efficacy population includes all patients who have received at least one dose of CPX-POM and had available tumor tissue at 
baseline and at the time of radical cystectomy. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 4 
Table 14.1-3.1 - Summary of Demographic and Baseline Characteristics 
(Safety Population) - Dose Escalation 
Page 16 of 125 
 
 
CPX-POM 
30 mg/m^2 
N=X 
CPX-POM 
[D2] mg/m^2 
N=X 
CPX-POM 
[D3] mg/m^2 
N=X 
CPX-POM 
[D4] mg/m^2 
N=X 
CPX-POM 
[D5] mg/m^2 
N=X 
CPX-POM 
[D6] mg/m^2 
N=X 
CPX-POM 
[D7] mg/m^2 
N=X 
 
 
Age [a] (years) 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Age group [n (%)] 
< 65 years 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
≥ 65 years 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Sex [n (%)] 
Male 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Female 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Race [n (%)] 
White 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Black or African American 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Asian 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
American Indian or Alaska Native 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Native Hawaiian or 
XX (XX.X) XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other Pacific Islander 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
[a] Age at Screening. 
[b] Body mass index (BMI) (kg/m²) = Weight (kg) / (Height (m))^2. 
[c] The denominator is the number of females in each dose group. 
[d] Body Surface Area (BSA) (m^2) = 0.007184 x Weight (kg)^0.425 x (Height (m))^0.725 (Dubois formula). 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 2 of 4 
Table 14.1-3.1 - Summary of Demographic and Baseline Characteristics 
(Safety Population) - Dose Escalation 
Page 17 of 125 
 
 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Female of child beari
[n (%)] [c] 
Able to bear childr
potential 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Premenarche 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Post Menopausal 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Sterile - of child bearing age 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Country [n (%)] 
XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
XXXXX 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Height (cm) 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
[a] Age at Screening. 
[b] Body mass index (BMI) (kg/m²) = Weight (kg) / (Height (m))**2. 
[c] The denominator is the number of females in each dose group. 
[d] Body Surface Area (BSA) (m^2) = 0.007184 x Weight (kg)^0.425 x (Height (m))^0.725 (Dubois formula). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 18 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 3 of 4 
 
Table 14.1-3.1 - Summary of Demographic and Baseline Characteristics 
(Safety Population) - Dose Escalation 
 
 
CPX-POM 
30 mg/m^2 
N=X 
CPX-POM 
[D2] mg/m^2 
N=X 
CPX-POM 
[D3] mg/m^2 
N=X 
CPX-POM 
[D4] mg/m^2 
N=X 
CPX-POM 
[D5] mg/m^2 
N=X 
CPX-POM 
[D6] mg/m^2 
N=X 
CPX-POM 
[D7] mg/m^2 
N=X 
 
 
Weight (kg) 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
BMI [b] (kg/m^2) 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
BSA [d] (m^2) 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
[a] Age at Screening. 
[b] Body Mass Index (BMI) (kg/m^2) = Weight (kg) / (Height (m))^2. 
[c] The denominator is the number of females in each dose group. 
[d] Body Surface Area (BSA) (m^2) = 0.007184 x Weight (kg)^0.425 x (Height (m))^0.725 (Dubois formula). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 19 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 4 of 4 
 
Table 14.1-3.1 - Summary of Demographic and Baseline Characteristics 
(Safety Population) - Dose Escalation 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
ECOG [n (%)] 
0 (Fully active) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
1 (Unable to perform physically 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
strenuous activity but ambulatory 
and able to carry out work of a 
light or sedentary nature) 
2 (Ambulatory and capable of all 
selfcare but unable to carry out 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
any work activities) 
3 (Capable of only limited 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
selfcare) 
4 (Completely disabled) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
[a] Age at Screening. 
[b] Body Mass Index (BMI) (kg/m^2) = Weight (kg) / (Height (m))^2. 
[c] The denominator is the number of females in each dose group. 
[d] Body Surface Area (BSA) (m^2) = 0.007184 x Weight (kg)^0.425 x (Height (m))^0.725 (Dubois formula). 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 20 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.1-3.2 - Summary of Demographic and Baseline Characteristics 
(Safety Population) - Expansion 
Replicate of Table 14.1-3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 21 of 125 
 
 
PROGRAMMING NOTES: 
• 
Categories are from the protocol deviations criteria form, the table only shows examples. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Table 14.1-4.1 - Important Protocol Deviations 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 [D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Protocol Deviations Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Any Important Protocol Deviations 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Inclusion / Exclusion Criteria 
INCL01 
XX 
<cont.> 
(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Prohibited Medications 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
 
<cont.> 
 
A patient could be counted under more than one category. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Table 14.1-4.2 - Important Protocol Deviations 
(Safety Population) - Expansion 
Replicate of Table 14.1-4.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 22 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 4 
 
Table 14.1-5.1.1 - Disease Characteristics 
(Safety Population) - Dose Escalation 
 
 
 
 
Primary Tumor Site [n (%)] 
CPX-POM 
30 mg/m^2 
N=X 
CPX-POM 
[D2] mg/m^2 
N=X 
CPX-POM 
[D3] mg/m^2 
N=X 
CPX-POM 
[D4] mg/m^2 
N=X 
CPX-POM 
[D5] mg/m^2 
N=X 
CPX-POM 
[D6] mg/m^2 
N=X 
CPX-POM 
[D7] mg/m^2 
N=X 
Bladder Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Breast Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Colon Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Gastric Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Head and Neck Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Liver 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Ovarian 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Prostate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
… 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Time Since 
n 
First Diagnosis of Cancer (months) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Disease 
1 
Stage at Screening Visit Date? [n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Presence 
No 
of Metastases? [n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 23 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 2 of 4 
 
Table 14.1-5.1.1 - Disease Characteristics 
(Safety Population) - Dose Escalation 
 
 
 
 
Extent of Current Metastatic disease 
CPX-POM 
30 mg/m^2 
N=X 
CPX-POM 
[D2] mg/m^2 
N=X 
CPX-POM 
[D3] mg/m^2 
N=X 
CPX-POM 
[D4] mg/m^2 
N=X 
CPX-POM 
[D5] mg/m^2 
N=X 
CPX-POM 
[D6] mg/m^2 
N=X 
CPX-POM 
[D7] mg/m^2 
N=X 
 
Abdomen/Viscera? [n (%)] 
No 
Yes 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
Adrenals? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Bladder? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Bone? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Bone Marrow? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Chest Wall? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
CNS/Brain? 
No 
[n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Kidnet? 
No 
[n (%)] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 24 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 3 of 4 
 
Table 14.1-5.1.1 - Disease Characteristics 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Lungs? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Liver? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Lymp Nodes? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Pancreas? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Peritoneal? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Plura? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Stomach? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Spleen? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other? [n (%)] 
No 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 25 of 125 
 
 
 
 
PROGRAMMING NOTES: 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 26 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 3 of 4 
 
Table 14.1-5.1.2 - Disease Characteristics 
(Safety Population) - Expansion 
 
Cisplatin 
ineligible 
N=X 
Chemotherapy 
eligible 
N=X 
Overall 
N=X 
n (%) 
n (%) 
n (%) 
Dose expansion Arm 
Cisplatin-ineligible patient 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Chemotherapy-eligible patient 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Reason [a] 
Creatinine clearance < 60 mL/min 
XX (XX.X) 
XX (XX.X) 
Heart failure (NYHA class >=III) 
XX (XX.X) 
XX (XX.X) 
Grade >=2 hearing loss 
XX (XX.X) 
XX (XX.X) 
Grade >=2 neuropathy 
XX (XX.X) 
XX (XX.X) 
Other 
XX (XX.X) 
XX (XX.X) 
Screening 
n 
eGFR (mL/min/1.73m2) 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
Minimum 
Median 
Maximum 
XX 
XX.X 
XX 
XX 
XX.X 
XX 
XX 
XX.X 
XX 
 
eGFR = estimated Glomerular Filtration Rate. 
[a] Applicable to Cisplatin ineligible group only . 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 27 of 125 
 
 
PROGRAMMING NOTES: 
• 
The Primary System Organ Classes are presented by alphabetical order and the Preferred Terms are sorted within Primary 
System Organ Classes by alphabetical order. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.1-5.2.1 - Other Medical History 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
[D3] 
CPX-POM 
[D4] 
CPX-POM 
CPX-POM 
[D6] 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
mg/m^2 
mg/m^2 
[D5] mg/m^2 
mg/m^2 
[D7] mg/m^2 
System Organ Class/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Preferred Term 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
At least one other previous 
condition? 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
System Organ Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
System Organ Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
If there was more than one condition reported under the same System Organ Class and Preferred Term, the patient was counted only 
once under that System Organ Class and Preferred Term. If there was more than one condition reported under the same System Organ 
Class, the patient was counted only once under that System Organ Class. 
MedDRA version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 28 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
Add footnote: ‘Events with both start and end dates missing were considered as concomitant.’ 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.1-5.2.2 - Other Medical History 
(Safety Population) - Expansion 
Replicate of Table 14.1-5.2.1 
 
 
 
 
Table 14.1-5.3.1 - Concomitant Diseases 
(Safety Population) - Dose Escalation 
Replicate of Table 14.1-5.2.1 
 
 
 
 
 
Table 14.1-5.3.2 - Concomitant Diseases 
(Safety Population) - Expansion 
Replicate of Table 14.1-5.3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 29 of 125 
 
 
PROGRAMMING NOTES: 
• 
The Therapeutic Classes are presented by alphabetical order and the Preferred Terms are sorted within Therapeutic Classes 
by alphabetical order. 
• 
A medication / therapy can appear within more than one Therapeutic Class. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Table 14.1-6.1.1 - Prior Medications by Therapeutic Class and Preferred Term 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Therapeutic Class/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Preferred Term 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
At least one prior medication? 
XX (XX.X) 
XX (XX.X) 
XX(XX.X) 
XX (XX.X) 
XX(XX.X) 
XX(XX.X) 
XX(XX.X) 
Therapeutic Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Therapeutic Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
A prior medication is a medication whose end date is before the date of first CPX-POM dose. 
If there was more than one prior medication reported under the same Therapeutic Class and Preferred Term, the patient was counted 
only once under that Therapeutic Class and Preferred Term. If there was more than one prior medication reported under the same 
Therapeutic Class, the patient was counted only once under that Therapeutic Class. 
WHO-DRUG version <version number>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 30 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
Update foootnote: replace ‘A prior medication is a medication whose end date is before the date of first CPX-POM dose’ by 
‘A concomitant medication is a medication that started before the date of first dose and stopped on (or is ongoing after) 
the date of first dose OR a medication whose start date is either the same as (or after) the date of first dose’. 
• 
Update ‘At least one prior medication’ by ‘At least one concomitant medication’. 
• 
The Therapeutic Classes are presented by alphabetical order and the Preferred Terms are sorted within Therapeutic Classes 
by alphabetical order. 
• 
A medication / therapy can appear within more than one Therapeutic Class. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
Table 14.1-6.1.2 - Prior Medications by Therapeutic Class and Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.1-6.1.1 
 
 
 
Table 14.1-6.2.1 - Concomitant Medications by Therapeutic Class and Preferred Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.1-6.1.1 
 
 
Table 14.1-6.2.2 - Concomitant Medications by Therapeutic Class and Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.1-6.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 31 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
 
Table 14.1-7.1 - Overall Exposure to Study Drug and Drug Compliance 
(Safety Population) - Dose Escalation 
 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
[D7] 
30 mg/m^2 
N=X 
[D2] mg/m^2 
N=X 
[D3] 
N=X 
mg/m^2 [D4] 
N=X 
mg/m^2 [D5] 
N=X 
mg/m^2 
[D6] 
N=X 
mg/m^2 
mg/m^2 
N=X 
Study Drug Exposure (days) [a] 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Study Drug Exposure (mg) [b] 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
 
[a]  The CPX-POM exposure expressed in days is calculated from the dose administration entered in the database as (last dose 
taken date - first dose taken date + 1) + 16. 
[b]  The CPX-POM exposure expressed in mg is calculated from the dose per m^2 entered in the database as the sum of all (dose 
per m^2 x Body Surface Area), using Body Surface Area calculated at baseline for Cycle 1 and Cycle 2 dose administrations, 
and calculated on Day 1 of every other treatment cycle from Cycle 3 dose administration. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 32 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
 
 
 
 
Table 14.1-7.2 - Overall Exposure to Study Drug and Drug Compliance 
(Safety Population) - Expansion 
Replicate of Table 14.1-7.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 33 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Tables 14.2 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 2 
 
Table 14.2-1.1 - Patients who have had at least one other post-baseline tumor assessment 
(Efficacy Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
At least one other 
tumor assessment 
post-baseline 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Primary Tumor Type [n (%)] 
Bladder Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Breast Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Carcinomatosis 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Colon Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Pancreatic Cancer 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
<etc> 
 
Note: A subject with overall response but no detailed tumor assessments is considered as having tumor assessment in this table. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 34 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 2 
 
 
Table 14.2-2.1 - Summary of Patients Responses 
(Efficacy Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Visit/ 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 
[D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Type of Response 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Cycle 2-Day 1 Visit 
Target Lesion Response [n (%)] 
Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Stable Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Non-Target Lesion Response [n (%)] 
Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Stable Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Overall Response [n (%)] 
Complete Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Partial Response 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Stable Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Progressive Disease 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Not evaluable 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
<repeat for Day 1 visit of each cycle from Cycle 3 to last Cycle number over all patients> 
Percentage was based on the number of patients with non-missing tumor assessment at each visit. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 35 of 125 
 
 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 36 of 125 
 
 
PROGRAMMING NOTES: 
• 
If the median time to event has not been reached, present as “NR (xx.x, xx.x)” [replacing xx.x with ‘-‘ if there is no 
upper or lower confidence limit]. 
• 
Time categories to be updated dependent upon the data. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 2 
Table 14.2-3.2 - 
(Efficacy 
Recurrence-Free Survival (RFS) 
Population) - Expansion 
Cisplatin 
ineligible 
Chemotherapy 
eligible 
Overall 
N=X 
N=X 
N=X 
Included in the analysis 
No. of events (%) 
No. of censored observations (%) 
XX 
XX (XX.X) 
XX (XX.X) 
XX 
XX (XX.X) 
XX (XX.X) 
XX 
XX (XX.X) 
XX (XX.X) 
Recurrence-Free Survival Time (Months) 
Minimum 
[a] 
XX.X 
XX.X 
XX.X 
25% quartile 
XX.X 
XX.X 
XX.X 
Median (95% CI) 
75% quartile 
Maximum 
[b] 
XX.X 
XX.X 
XX.X 
(XX.X; XX.X) 
XX.X 
XX.X 
XX.X 
(XX.X; XX.X) 
XX.X (XX.X; 
XX.X 
XX.X 
XX.X) 
 
KM probability estimate for Recurrence-Free Survival rate (95% CI) [c] 
3 months 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
6 months 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
12 months 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
… 
 
[a] Kaplan-Meier estimates. 
[b] 95% confidence interval (CI) for median recurrence-free survival is calculated using the Brookmeyer and Crowley method. 
[c] Probability estimates are based upon Kaplan-Meier estimates and 95% CI use the log-log transformation. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 37 of 125 
 
 
PROGRAMMING NOTES: 
• 
Replace ‘Recurrence-Free Survival’ by ‘Overall Survival’ in the table and footnotes. 
Table 14.2-4.2 - Overall Survival (OS) 
(Efficacy Population) - Expansion 
Replicate of Table 14.2-3.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 38 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
 
Table 14.2-5.2 - Patients who Undergo Radical Cystectomy 
(Efficacy Population) - Expansion 
 
 
Cisplatin 
ineligible 
N=X 
n (%) 
Chemotherapy 
eligible 
N=X 
n (%) 
Overall 
N=X 
n (%) 
 
 
Number of patients who undergo 
radical cystectomy 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 39 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Tables 14.3 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
 
Table 14.3-1.0 - Dose-Limiting Toxicity (DLT) 
(Safety Population) - Dose Escalation 
 
 
CPX-POM 
30 mg/m^2 
CPX-POM 
[D2] mg/m^2 
CPX-POM 
[D3] mg/m^2 
CPX-POM 
[D4] mg/m^2 
CPX-POM 
[D5] mg/m^2 
CPX-POM 
[D6] mg/m^2 
CPX-POM 
[D7] mg/m^2 
 
 
 
 
at least one DLT 
 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Number of patients with 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
MedDRA version <version number>. 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 40 of 125 
 
 
PROGRAMMING NOTES: 
• 
“Leading to discontinuation” is derived from action taken = permanently discontinued. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
 
Table 14.3-1.1.1 - Overview of Adverse Events 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Number of patie
at least one: 
with 
AE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
TEAE * 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Related TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
TEAE leading to discontinuation 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Related TEAE leading to 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
discontinuation 
Serious TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Serious related TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
* A treatment-emergent adverse events (TEAE) is defined as an adverse event that started on or after the first dose of CPX-POM 
administration. 
MedDRA version <version number>. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 41 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
• 
Replace footnote ‘* A treatment-emergent adverse events (TEAE) is defined as an adverse event that started on or after 
the first dose of CPX-POM administration’ by ‘* A treatment-emergent adverse events (TEAE) is defined as an adverse event 
that started on or after the first dose of CPX-POM administration and before the date of the last CPX-POM dose + 30 days 
or the date of start of a new anti-cancer therapy or the date of radical cystectomy, whichever occurs first.’ 
 
Table 14.3-1.1.2 - Overview of Adverse Events 
(Safety Population) - Expansion 
 
Replicate of Table 14.3-1.1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 42 of 125 
 
 
PROGRAMMING NOTES: 
• 
The System Organ Classes are presented by decreasing frequency (within the total column - all CPX-POM doses groups 
combined) and the Preferred Terms within a System Organ Class are presented by decreasing frequency (within the total 
column - all CPX-POM doses groups combined). 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-1.2.1 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
System Organ Class 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Preferred Term 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Number of patients with 
at least one TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
System Organ Class #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
System Organ Class #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
 
If there was more than one TEAE reported under the same System Organ Class and Preferred Term, the patient was counted only once 
under that System Organ Class and that Preferred Term. If there was more than one TEAE reported under the same System Organ Class, 
the patient was counted only once under that System Organ Class. 
MedDRA version <version number>. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 43 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
Adjust footnote to mention ‘related TEAE’ instead of ‘TEAE’. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
 
Table 14.3-1.2.2 - Number (%) of Patients with Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.2.1 
 
 
 
 
Table 14.3-1.3.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.2.1 
 
 
 
 
Table 14.3-1.3.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 44 of 125 
 
 
PROGRAMMING NOTES: 
• 
Adjust footnote to mention ‘serious TEAE’ instead of ‘TEAE’. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
Adjust footnote to mention ‘serious related TEAE’ instead of ‘TEAE’. 
Table 14.3-1.4.1 - Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.2.1 
 
 
 
 
Table 14.3-1.4.2 - Number (%) of Patients with Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.4.1 
 
 
 
 
Table 14.3-1.5.1 - Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 45 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
“Leading to discontinuation” is derived from Did AE lead to study discontinuation? = Yes. 
• 
Adjust footnote to mention ‘TEAE leading to discontinuation’ instead of ‘TEAE’. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
Table 14.3-1.5.2 - Number (%) of Patients with Serious Related Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.5.1 
 
 
 
 
Table 14.3-1.6.1 - Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by System Organ 
Class and Preferred Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.2.1 
 
 
 
 
Table 14.3-1.6.2 - Number (%) of Patients with Treatment-Emergent Adverse Events Leading to Discontinuation by System Organ 
Class and Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.6.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 46 of 125 
 
 
PROGRAMMING NOTES: 
• 
“Leading to discontinuation” is derived from Did AE lead to study discontinuation? = Yes. 
• 
Adjust footnote to mention ‘related TEAE leading to discontinuation’ instead of ‘TEAE’. 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
Table 14.3-1.7.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events Leading to Discontinuation by System 
Organ Class and Preferred Term 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.2.1 
 
 
 
Table 14.3-1.7.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events Leading to Discontinuation by System 
Organ Class and Preferred Term 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.7.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 47 of 125 
 
 
PROGRAMMING NOTES: 
• 
Display all severities even if there are no patients. 
• 
The System Organ Classes are presented by alphabetically. 
• 
‘CPX-POM All Doses’ will also be displayed. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Table 14.3-1.8.1 - Number (%) of Patients with Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximal Severity 
(Safety Population) - Dose Escalation 
 
Dose group: CPX-POM 30 mg/m^2 (N=X) 
System Organ Class 
Preferred Term 
Any CTC 
grade 
CTC grade 1 CTC grade 2 
CTC grade 3 CTC grade 4 CTC grade 5 
Maximal severity 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Number of patients with any TEAE 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
System Organ Class #1 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<etc> 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
System Organ Class #2 
Preferred Term #1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred Term #2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Preferred 
<etc> 
Term #3 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
XX 
XX 
(XX.X) 
(XX.X) 
 
If there was more than one TEAE reported under the same System Organ Class and Preferred Term, the patient was counted only once 
under the maximal severity for that System Organ Class and Preferred Term. If there was more than one TEAE reported under the 
same System Organ Class, the patient was counted only once under the maximal severity for that System Organ Class. 
MedDRA version <version number>. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 48 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three groups: ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
PROGRAMMING NOTES: 
• 
Adjust footnote to mention ‘related TEAE’ instead of ‘TEAE’. 
PROGRAMMING NOTES: 
• 
Include three groups: ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
 
Table 14.3-1.8.2 - Number (%) of Patients with Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximal Severity 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.8.1 
 
 
 
 
 
Table 14.3-1.9.1 - Number (%) of Patients with Related Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximum Severity 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-1.8 
 
 
 
 
 
Table 14.3-1.9.2 - Number (%) of Patients with Related Treatment-Emergent Adverse Events 
by System Organ Class, Preferred Term and Maximum Severity 
(Safety Population) - Expansion 
Replicate of Table 14.3-1.9.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 49 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.1.1 - Summary of Hematology Laboratory Data 
(Safety Population) - Dose Escalation 
 
Laboratory Parameter: Hemoglobin (unit) 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 
[D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
BAS [a] 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
C1 TRT D4 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Change from BAS 
to C1 TRT D4 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Minimum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Maximum 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
<repeat for Cycle 1 Day 10 visit> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 4 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit> 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 50 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
 
 
 
Table 14.3-2.1.1.2 - Summary of Hematology Laboratory Data 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.1 
 
PROGRAMMING NOTES: 
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count and 
Differential (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils). 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 51 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all doses groups, including ‘CPX-POM All Doses’. 
• 
Repeat for all hematology parameters: Hemoglobin, Hematocrit, Platelet count, RBC count, Reticulocytes, WBC Count and 
Differential (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils). 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.2.1 - Outside of Normal Range - Shift Table for Hematology Laboratory Parameters 
(Safety Population) - Dose Escalation 
 
Dose group: CPX-POM 30 mg/m^2 (N=X) 
 
Baseline [a] value 
Parameter/ 
Visit 
Hemoglobin (unit) 
Value 
at Visit 
Low 
n (%) 
Normal 
n (%) 
High 
n (%) 
Low/High* 
n (%) 
Total 
 
C1 TRT D4 (N**=XX) 
Low 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
High 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Low/High* 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C1 TRT D10 (N**=XX) 
Low 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
High 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Low/High* 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 4 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit> 
<repeat for all doses groups> 
 
Percentage was based on the number of patients present at each visit with non-missing results for the considered parameter. 
* Includes patients with Low or High results. ** Denominator of the percentage. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 52 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.3-2.1.2.2 - Outside of Normal Range - Shift Table for Hematology Laboratory Parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 53 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all gradable hematology parameters. 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.3.1 - On-treatment Hematology Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 [D6] mg/m^2 [D7] mg/m^2 
Parameter/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Worst NCI-CTCAE grade 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Hemoglobin (unit) 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Hematocrit (unit) 
Normal 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 1 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 2 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 3 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Grade 4 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Missing 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<repeat for the other hematology parameters> 
 
A patient with multiple results for a parameter will only be counted once under the maximum NCI-CTCAE grade for this parameter. 
Laboratory ranges are based on NCI-CTCAE version 4.03. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 54 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.3-2.1.3.2 - On-treatment Hematology Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 55 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all doses groups, including ‘CPX-POM All Doses’. 
• 
Repeat for all gradable hematology parameters. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Table 14.3-2.1.4.1 - Shift table of Worst NCI-CTCAE Grade for Hematological parameters 
(Safety Population) - Dose Escalation 
 
Dose group: CPX-POM 30 mg/m^2 (N=X) 
 
Worst NCI-CTCAE grade 
Baseline 
Normal 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Missing 
Total 
Parameter 
grade 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Hematocrit (unit) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 1 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 2 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 3 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 4 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Missing 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Hemoglobin (unit) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 1 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 2 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 3 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Grade 4 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Missing 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<repeat for the other hematology parameters> 
 
A patient with multiple results for a parameter will only be counted under the maximum NCI-CTCAE grade for this parameter. 
Laboratory ranges are based on NCI-CTCAE version 4.03. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 56 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
 
Table 14.3-2.1.4.2 - Shift table of Worst NCI-CTCAE Grade for Hematological parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.4.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 57 of 125 
 
 
PROGRAMMING NOTES: 
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, Magnesium, Phosphate, 
Lipase, Amylase, Corrected Calcium 
PROGRAMMING NOTES: 
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, Magnesium, Phosphate, 
Lipase, Amylase, Corrected Calcium 
PROGRAMMING NOTES: 
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, Magnesium, Phosphate, 
Lipase, Amylase, Corrected Calcium 
 
 
Table 14.3-2.2.1.1 - Summary of Clinical Chemistry Laboratory Data 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.1.1 
 
 
 
Table 14.3-2.2.1.2 - Summary of Clinical Chemistry Laboratory Data 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.2 
 
 
 
 
Table 14.3-2.2.2.1 - Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 58 of 125 
 
 
PROGRAMMING NOTES: 
Clinical Chemistry parameters are: Potassium, Sodium, Chloride, Glucose, BUN, Creatinine, Creatinine clearance, ALP, ALT, AST, 
GGT, Direct bilirubin, Indirect bilirubin, Total bilirubin, Total protein, Albumin, Calcium, Bicarbonate, Magnesium, Phosphate, 
Lipase, Amylase, Corrected Calcium 
PROGRAMMING NOTES: 
Include all gradable Clinical Chemistry parameters 
PROGRAMMING NOTES: 
Include all gradable Clinical Chemistry parameters 
Table 14.3-2.2.2.2 - Outside of Normal Range - Shift Table for Clinical Chemistry Laboratory Parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.2.2 
 
 
 
 
Table 14.3-2.2.3.1 - On-treatment Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.3.1 
 
 
 
Table 14.3-2.2.3.2 - On-treatment Clinical Chemistry Adverse Events: Worst NCI-CTCAE Grade per patient 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.3.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 59 of 125 
 
 
PROGRAMMING NOTES: 
Include all gradable Clinical Chemistry parameters 
PROGRAMMING NOTES: 
Include all gradable Clinical Chemistry parameters 
 
Table 14.3-2.2.4.1 - Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters 
(Safety Population) - Dose Escalation 
 
Replicate of Table 14.3-2.1.4.1 
 
 
 
 
Table 14.3-2.2.4.2 - Shift table of Worst NCI-CTCAE Grade for Clinical Chemistry Laboratory parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.4.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 60 of 125 
 
 
PROGRAMMING NOTES: 
• 
Coagulation parameters are PT and aPTT. 
• 
Only Day 1 visit of each cycle 
PROGRAMMING NOTES: 
• 
Coagulation parameters are PT and aPTT. 
• 
Only Day 1 visit of each cycle 
PROGRAMMING NOTES: 
• 
Coagulation parameters are PT and aPTT. 
• 
Only Day 1 visit of each cycle. 
Table 14.3-2.3.1.1 - Summary of Coagulation Laboratory Data 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.1.1 
 
 
 
Table 14.3-2.3.1.2 - Summary of Coagulation Laboratory Data 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.2 
 
 
 
Table 14.3-2.3.2.1 - Outside of Normal Range - Shift Table for Coagulation Laboratory Parameters 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 61 of 125 
 
 
PROGRAMMING NOTES: 
• 
Coagulation parameters are PT and aPTT. 
• 
Only Day 1 visit of each cycle. 
 
 
Table 14.3-2.3.2.2 - Outside of Normal Range - Shift Table for Coagulation Laboratory Parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.2.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 62 of 125 
 
 
PROGRAMMING NOTES: 
• 
Thyroid Panel parameters are TSH, Free T4 and Free and total T3. 
• 
Only Day 1 visit of each cycle. 
PROGRAMMING NOTES: 
• 
Thyroid Panel parameters are TSH, Free T4 and Free and total T3. 
• 
Only Day 1 visit of each cycle. 
PROGRAMMING NOTES: 
• 
Thyroid Panel parameters are TSH, Free T4 and Free and total T3. 
• 
Only Day 1 visit of each cycle. 
 
Table 14.3-2.4.1.1 - Summary of Thyroid Panel Laboratory Data 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.1.1 
 
 
 
 
Table 14.3-2.4.1.2 - Summary of Thyroid Panel Laboratory Data 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.2 
 
 
 
Table 14.3-2.4.2.1 - Outside of Normal Range - Shift Table for Thyroid Panel Laboratory Parameters 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 63 of 125 
 
 
PROGRAMMING NOTES: 
• 
Thyroid Panel parameters are TSH, Free T4 and Free and total T3. 
• 
Only Day 1 visit of each cycle. 
 
Table 14.3-2.4.2.2 - Outside of Normal Range - Shift Table for Thyroid Panel Laboratory Parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.2.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 64 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 1 
 
 
 
Table 14.3-2.5.1 - Summary of Other Laboratory Data 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Visit/ 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Parameter 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
SCR 
Pregnancy test? 
Negative 
[n (%)] [a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Positive 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
BAS 
Pregnancy test? 
Negative 
[n (%)][a] 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Positive 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
<for Pregnancy test, repeat for Day 1 visit of each cycle> 
 
[a] Denominator for the percentages was the number of females of child bearing potential. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 65 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.3-2.5.2 - Summary of Other Laboratory Data 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.6.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 66 of 125 
 
 
PROGRAMMING NOTES: 
• 
Update “laboratory parameter” by “parameter”. 
• 
Vital signs include pulse rate, blood pressure, respiratory rate, oxygen saturation and temperature. 
• 
On Days 1 and 5, vital signs are measured at pre-dose and at 6-hour intervals post-dose. 
PROGRAMMING NOTES: 
• 
Update “laboratory parameter” by “parameter”. 
• 
Vital signs include pulse rate, blood pressure, respiratory rate, oxygen saturation and temperature. 
• 
On Days 1 and 5, vital signs are measured at pre-dose and at 6-hour intervals post-dose. 
 
Table 14.3-3.1.1 - Summary of Vital Signs 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.1.1 
 
 
 
Table 14.3-3.1.2 - Summary of Vital Signs 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 67 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of 3 
 
 
Table 14.3-3.2.1 - Summary of Abnormal Vital Signs 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Parameter/ 
30 mg/m^2 
[D2] mg/m^2 [D3] mg/m^2 [D4] mg/m^2 
[D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Visit/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Pulse rate (bpm) [b] 
BAS [a] * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
> 150 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[101-150] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 55 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C1 TRT D2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
> 150 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[101-150] bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 55 bpm 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Total number of abnormal results at each visit, used as the denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
[b] Pulse rate: > 150 bpm: Very High values; [101-150] bpm: High values; < 55 bpm: Low values. 
[c] Systolic Blood Pressure: >= 161 mmHg: Very High values; [131-160] mmHg: High values; < 95 mmHg: Low values. 
[d] Diastolic Blood Pressure: >= 101 mmHg: Very High values; [86-100] mmHg: High values; < 50 mmHg: Low values. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 68 of 125 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 2 of 3 
 
 
Table 14.3-3.2.1 - Summary of Abnormal Vital Signs 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Parameter/ 
30 mg/m^2 
[D2] mg/m^2 [D3] mg/m^2 
[D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Visit/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Systolic Blood
BAS [a] * 
(mmHg) [c] 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
>= 161 mmH
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[131-160] mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 95 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C1 TRT D2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
>= 161 mmH
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[131-160] 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 95 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Total number of abnormal results at each visit, used as the denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
[b] Pulse rate: > 150 bpm: Very High values; [101-150] bpm: High values; < 55 bpm: Low values. 
[c] Systolic Blood Pressure: >= 161 mmHg: Very High values; [131-160] mmHg: High values; < 95 mmHg: Low values. 
[d] Diastolic Blood Pressure: >= 101 mmHg: Very High values; [86-100] mmHg: High values; < 50 mmHg: Low values. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 69 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 3 of 3 
 
 
Table 14.3-3.2.1 - Summary of Abnormal Vital Signs 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Parameter/ 
30 mg/m^2 
[D2] mg/m^2 [D3] mg/m^2 [D4] mg/m^2 
[D5] mg/m^2 
[D6] mg/m^2 
[D7] mg/m^2 
Visit/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Diastolic Blood Pressure (mmHg) [d] 
BAS [a] * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
>= 101 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[86-100] mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 50 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C1 TRT D2 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
>= 101 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
[86-100] mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
< 50 mmHg 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
 
<repeat for next Cycle 1 visits> 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit to Day 6 visit> 
<for the last Cycle, repeat for Day 1 visit to Day 6 visit, Day 22 visit and Day 28 follow-up visit> 
 
* Total number of abnormal results at each visit, used as the denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
[b] Pulse rate: > 150 bpm: Very High values; [101-150] bpm: High values; < 55 bpm: Low values. 
[c] Systolic Blood Pressure: >= 161 mmHg: Very High values; [131-160] mmHg: High values; < 95 mmHg: Low values. 
[d] Diastolic Blood Pressure: >= 101 mmHg: Very High values; [86-100] mmHg: High values; < 50 mmHg: Low values. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 70 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
Table 14.3-3.2.2 - Summary of Abnormal Vital Signs 
(Safety Population) - Expansion 
Replicate of Table 14.3-3.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 71 of 125 
 
 
PROGRAMMING NOTES: 
• 
Update “laboratory parameter” by “ECG parameter”. 
• 
ECG parameters include Heart Rate, PR Interval, RR interval, QRS Duration, QT Interval, QTcF Interval. 
PROGRAMMING NOTES: 
• 
Update “laboratory parameter” by “ECG parameter”. 
• 
ECG parameters include Heart Rate, PR Interval, RR interval, QRS Duration, QT Interval, QTcF Interval. 
 
Table 14.3-4.1.1 - Summary of ECG Parameters 
(Safety Population) - Dose Escalation 
Replicate of Table 14.3-2.1.1.1 
 
 
 
Table 14.3-4.1.2 - Summary of ECG Parameters 
(Safety Population) - Expansion 
Replicate of Table 14.3-2.1.1.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 72 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page X of Y 
 
 
Table 14.3-4.2.1 - Summary of Abnormal ECG Intervals 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Parameter/ 
30 mg/m^2 
[D2] mg/m^2 
[D3] mg/m^2 [D4] mg/m^2 
[D5] mg/m^2 [D6] mg/m^2 [D7] mg/m^2 
Visit/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
QTcF interval (msec) 
BAS [a]* 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
> 450 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
> 480 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
> 500 msec (CS) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C1 TRT D5 * 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
> 450 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
> 480 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
> 500 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Change from Baseline 
C1 TRT D5 * 
to 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
> 30 msec 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
> 60 msec (CS) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit> 
<for last cycle, repeat for Day 28 follow-up visit> 
 
* Total number of abnormal results at each visit, used as the denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
CS = Clinically Significant; NCS = Not Clinically Significant. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 73 of 125 
 
 
PROGRAMMING NOTES: 
• 
A last column with the header ‘CPX-POM All Doses’ will also be displayed. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page X of Y 
 
 
Table 14.3-4.2.1 - Summary of Abnormal ECG Intervals 
(Safety Population) - Dose Escalation 
 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
CPX-POM 
Parameter/ 
30 mg/m^2 
[D2] mg/m^2 [D3] mg/m^2 [D4] mg/m^2 [D5] mg/m^2 
[D6] mg/m^2 [D7] mg/m^2 
Visit/ 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
N=X 
Category 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
PR interval 
Percent Change from Baseline to 
C1 TRT D5 * 
≥ 50% increase from baseline if 
baseline < 200 ms 
≥ 25% increase from baseline if 
baseline ≥ 200 ms 
 
QRS duration 
Percent Change from Baseline to 
C1 TRT D5 * 
≥ 50% increase from baseline if 
baseline < 110 ms 
≥ 25% increase from baseline if 
baseline ≥ 110 ms 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit> 
<for last cycle, repeat for Day 28 follow-up visit> 
 
* Total number of abnormal results at each visit, used as the denominator for the percentages. 
[a] Baseline was the last value/result of assessment prior to or on day of first study treatment. 
CS = Clinically Significant; NCS = Not Clinically Significant. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 74 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
 
Table 14.3-4.2.2 - Summary of Abnormal ECG Intervals 
(Safety Population) - Expansion 
Replicate of Table 14.3-4.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 75 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all doses groups, including ‘CPX-POM All Doses’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Table 14.3-4.3.1 - Shift Table for ECG Overall Interpretation 
(Safety Population) - Dose Escalation 
 
Dose group : CPX-POM 30 mg/m^2 (N=X) 
 
Baseline [a] value 
 
Visit 
Value 
at Visit 
 
Normal n (%) 
Abnormal, CS n 
(%) 
Abnormal, 
NCS n (%) 
Total 
C1 TRT D5 (N*=XX) 
Normal 
Abnormal, 
Abnormal, 
Total 
CS 
NCS 
XX 
XX 
XX 
XX 
(XXX.X) 
(XXX.X) 
(XXX.X) 
(XXX.X) 
XX 
XX 
XX 
XX 
(XXX.X) 
(XXX.X) 
(XXX.X) 
(XXX.X) 
XX 
XX 
XX 
XX 
(XXX.X) 
(XXX.X) 
(XXX.X) 
(XXX.X) 
XX 
XX 
XX 
XX 
(XXX.X) 
(XXX.X) 
(XXX.X) 
(XXX.X) 
C2 TRT D1 (N*=XX) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
C2 TRT D5 (N*=XX) 
Normal 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Abnormal, CS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Abnormal, NCS 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
Total 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
XX (XXX.X) 
<for Cycle 2 to last-1 Cycle, repeat for Day 1 visit and Day 5 visit> 
<for the last Cycle, repeat for Day 22 visit and Day 28 follow-up visit> 
<repeat for all doses groups> 
 
Percentage was based on the number of patients present at each visit with non-missing results for the ECG overall interpretation. 
* Denominator of the percentage. 
[a] Baseline was the last value of assessment prior to or on day of first study treatment intake. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 76 of 125 
 
 
PROGRAMMING NOTES: 
• 
Include three columns for ‘Cisplatin ineligible’,‘Chemotherapy eligible’,‘Overall’. 
 
Table 14.3-4.3.1 - Shift Table for ECG Overall Interpretation 
(Safety Population) - Expansion 
Replicate of Table 14.3-4.3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 77 of 125 
 
 
PROGRAMMING NOTES: 
• 
Add legend for group labels accordingly: ‘Cisplatin ineligible’,‘Chemotherapy eligible’. 
• 
X-axis - Label “Recurrence-free survival (months)”, Y-axis - Label “Survival probability (%).” 
• 
Legend: “Median” and 95% CI. 
• 
Flag censored observations with ‘+’ and add legend. 
• 
If the median time to event has not been reached, present as “Median (95% CI) NR (xx.x, xx.x)” [replacing xx.x with ‘- 
‘ if there is no upper or lower confidence limit] and add footnote: NR = Median time not reached. 
Figures 
 
Figure 14.2-4.2 - Recurrence-Free Survival (RFS) 
(Efficacy Population) – Expansion 
 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 78 of 125 
 
 
PROGRAMMING NOTES: 
• 
Replace ‘Recurrence-Free Survival’ by ‘Overall Survival’ in the figure. 
 
Figure 14.2-5.2 - Overall Survival (OS) 
(Efficacy Population) - Expansion 
Replicate of Figure 14.2-4.2 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 79 of 125 
 
 
PROGRAMMING NOTES: 
• 
List all Inclusion / Exclusion criteria as per eCRF. 
• 
Note: Inclusion / Exclusion text displayed in the listing shell is based on the text in Protocol Version 3.0, but all 
Inclusion / Exclusion criteria for each of the protocol version (initial to last) should be listed. 
Listings 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.1-1.1.1 - Preface to Inclusion and Exclusion Criteria - Dose Escalation 
 
 
Protocol 
Version 
Inclusion/ 
Exclusion No. 
Inclusion / Exclusion Text 
 
3.0    INCL01    Patient has histologically- or cytologically- confirmed metastatic or advanced-stage solid malignant 
tumor that is refractory to standard therapy. Patients should only be included if no therapy exists 
or if they have received all standard therapies that would be potentially curative or might provide 
significant benefit. 
INCL02   Patient may have received up to 4 prior lines of cytotoxic chemotherapy or immunotherapy for their 
metastatic disease (e.g., docetaxel + doxorubicin ± cyclophosphamide), and also may have received 
additional prior endocrine therapy, as appropriate (e.g., for breast or prostate cancer), or non- 
myelosuppressive therapy (e.g., bevacizumab, trastuzumab). 
<etc> 
 
EXCL01 
Patient has a history of risk factors for torsade de pointes (e.g., heart failure, hypokalemia, 
family history of long QT syndrome) or requires the use of concomitant medications that prolong the 
QT/QTc interval during study participation. 
EXCL02 
Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or computed 
tomography (CT) scan. 
<etc> 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 80 of 125 
 
 
PROGRAMMING NOTES: 
• 
List all Inclusion / Exclusion criteria as per eCRF. 
• 
Note: as expansion has been added in PA5, all Inclusion / Exclusion criteria for each of the protocol version from PA5 
should be listed. 
• 
Add footnote: 
Expansion has been added to the protocol from version 5.0. 
 
 
 
Listing 16.2.1-1.1.2 - Preface to Inclusion and Exclusion Criteria - Expansion 
Replicate of Listing 16.2.1-1.1.1 
 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 81 of 125 
 
 
PROGRAMMING NOTES: 
• 
List all Inclusion / Exclusion criteria that are failed (i.e. ‘N’ for inclusion and ‘Y’ for exclusion) 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.1-1.2.1 - List of Failed Inclusion and Exclusion Criteria 
(All Patients) - Dose Escalation 
 
 
Center/ CPX-POM 
Protocol 
Patient Dose group 
Version 
Failed Inclusion / Exclusion 
XXXX 
[D3] mg/m^2 
3.0 
INCL01 
EXCL05 
xxxxxxxxxxxxxxxxx, INCL09 xxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxx, EXCL08 xxxxxxxxxxxxxxxxx, EXCl10 xxxxxxxxxxxxxxxxx 
XXXX 
[D5] mg/m^2 
3.0 
INCL02 
EXCL03 
xxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxx, EXCL07 xxxxxxxxxxxxxxxxx 
<to be completed with the other patients having at least one protocol deviation> 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
 
 
 
 
Listing 16.2.1-1.2.2 - List of Failed Inclusion and Exclusion Criteria 
(All Patients) - Expansion 
Replicate of Listing 16.2.1-1.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 82 of 125 
 
 
(XXX) 
(XXX) 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.1-2.1 - Patient Disposition 
(Safety Population) - Dose Escalation 
 
Did the patient 
complete a full 
cycle (including Day 
Date (day) of 
Reason for 
Date 
Center/ 
CPX-POM 
22 assessments) and 
Discontinuation/ 
Discontinuation, 
(day) of 
Date (day) 
Reason 
Patient 
Country 
Dose group 
the Follow Up Visit? 
Completion 
specify 
Last Dose 
of Death 
for Death 
 
XXXX 
XXX 
30 mg/m^2 
Yes 
DDMMMYYYY (XXX) 
DDMMMYYYY 
XXXX 
XXX 
[D2] mg/m^2 Yes 
DDMMMYYYY (XXX) 
DDMMMYYYY 
DDMMMYYYY 
(XXX) 
DDMMMYYYY 
(XXX) 
Adverse Event 
DDMMMYYYY 
(XXX) 
DDMMMYYYY 
(XXX) 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
XXXX 
XXXX 
XXX 
XXX 
[D3] 
[D4] 
mg/m^2 
mg/m^2 
Yes 
Yes 
DDMMMYYYY 
DDMMMYYYY 
(XXX) 
(XXX) 
XXXX 
XXX 
[D4] mg/m^2 No 
DDMMMYYYY (XXX) 
XXXX 
XXX 
[D4] mg/m^2 Yes 
DDMMMYYYY (XXX) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 83 of 125 
 
 
up 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.1-2.2 - Patient Disposition 
(Safety Population) - Expansion 
 
Completed end of 
Treatment Visit (Day 
Date (day) of 
42 or Day 64)/ 
Treatment Visit 
Center/ 
Reason for Treatment 
Completion / 
Date (day) of 
Date (day) of 
Reason for 
Patient 
Country Group 
Discontinuation 
Discontinuation 
Last Dose 
End of Study 
End of Study 
 
XXXX 
 
XXXX 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) DDMMMYYYY (XXX) 
Lost to Follow 
XXX 
Chemotherapy 
eligible 
XXXX 
XXX 
Cisplatin 
ineligible 
XXXX 
XXX 
Chemotherapy 
eligible 
XXXX 
XXX 
Cisplatin 
ineligible 
Yes 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
Yes 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
 
No / Adverse Event 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) DDMMMYYYY (XXX) 
Withdrawn 
Consent 
Yes 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
XXXX 
XXX 
Cisplatin 
Yes 
ineligible 
XXX 
Chemotherapy 
Yes 
eligible 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 84 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.2.1 - Protocol Deviations 
(Safety Population) - Dose Escalation 
 
 
Center/ 
Patient 
CPX-POM 
Dose group 
Category 
Description 
Comment 
Leading to Exclusion 
from Analysis 
Population(s) 
Classification 
 
XXXX 
[D4] mg/m^2 Compliance 
Not treated 
xxxxxxx 
Safety / Efficacy 
<to be completed with the other patients having at least one protocol deviation> 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Listing 16.2.2.2 - Protocol Deviations 
(Safety Population) - Expansion 
Replicate of Listing 16.2.2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 85 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Replace definition of efficacy population in footnote by ‘The Efficacy population consists of all patients who have 
received at least one dose of CPX-POM and had tumor tissue at baseline and at the time of RC.’ 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.3.1 - Analysis Populations 
(Safety Population) - Dose Escalation 
 
 
 
Center/ 
Patient 
Country 
CPX-POM 
Dose group 
Safety Population 
Efficacy Population 
 
XXXX 
XXX 
30 mg/m^2 
Yes 
Yes 
XXXX 
XXX 
[D2] mg/m^2 
Yes 
Yes 
XXXX 
XXX 
[D3] mg/m^2 
Yes 
No 
XXXX 
XXX 
[D4] mg/m^2 
Yes 
Yes 
XXXX 
XXX 
[D4] mg/m^2 
No 
No 
XXXX 
XXX 
[D4] mg/m^2 
Yes 
Yes 
<etc> 
 
The safety population consists of all patients who received at least one dose of CPX-POM. 
The efficacy population consists of all patients who have received at least one dose of CPX-POM, had RECIST measurable disease 
at baseline and had at least one other post-baseline tumor assessment. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Listing 16.2.3.2 - Analysis Populations 
(Safety Population) - Expansion 
Replicate of Listing 16.2.3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 86 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.4-1.1 - Demographic and Baseline Characteristics 
(Safety Population) - Dose Escalation 
Center/ 
CPX-POM 
Age 
Weight 
Height 
BMI 
BSA 
Female of 
Child Bearing 
ECOG 
Patient Country Dose group 
(year) 
Sex 
Race 
(kg) 
(cm) 
(kg/m^2) 
(kgxm) 
Potential? 
[a] 
XXXX 
XXX 
30 mg/m^2 
XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
XXX 
XXXX 
XXX 
[D2] mg/m^2 
XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
Yes 
XXX 
XXXX 
XXX 
[D3] mg/m^2 
XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
No 
XXX 
XXXX 
XXX 
[D4] mg/m^2 
XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
XXX 
XXXX 
XXX 
[D4] mg/m^2 
XX 
Male 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
XXX 
XXXX 
XXX 
[D4] mg/m^2 
XX 
Female 
XXXXX 
XXX.X 
XXX 
XX.X 
XX.X 
No 
XXX 
<etc> 
 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. Age was calculated from date of birth and date 
of screening. BMI (kg/m²)= Weight (kg)/Height (m)^2. BSA (kgxm) = 0.007184 x Weight (kg)^0.425 x (Height (cm))^0.725 (Dubois 
formula). 
[a] 0 = Fully active. Able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous 
activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light house work and office work; 2 
= Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking 
hours; 3 = Capable of only limited selfcare. Confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. 
Cannot carry on any selfcare. Totally confined to bed or chair. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 87 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.4-1.2 - Demographic and Baseline Characteristics 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 88 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.4-2.1 - Pregnancy Test Results 
(Safety Population) - Dose Escalation 
 
 
Center/ 
Patient 
CPX-POM 
Dose group 
Visit 
Parameter 
Assessment 
Performed? 
Assessment 
Date 
Study 
Day 
Result 
XXXX 
30 mg/m^2 
SCR 
Pregnancy Test 
Yes 
DDMMMYYYY 
XX 
Negative 
BAS 
Pregnancy Test 
Yes 
DDMMMYYYY 
XX 
Positive 
<repeat 
<cont.> 
for Day 1 of next cycles if relevant> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
Only females are included in this listing. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Listing 16.2.4-2.2 - Pregnancy Test Results 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 89 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Listing 16.2.4-3.1 - Cancer History 
(Safety Population) - Dose Escalation 
 
Center/ 
Patient 
CPX-POM 
Dose group 
Primary 
Type 
Tumor 
Initial Histological 
or Cytological 
Diagnosis 
Date (Day) 
Disease 
Stage at 
Screening 
Presence of 
Metastases? 
Location 
XXXX 
30 mg/m^2 
XXXXX 
DDMMMYYYY (XXX) 
Grade X 
No 
XXXX 
[D2] mg/m^2 XXXXX 
DDMMMYYYY (XXX) 
Grade X 
No 
XXXX 
[D3] mg/m^2 XXXXX 
DDMMMYYYY (XXX) 
Grade X 
Yes 
Adrenals/ Bone 
XXXX 
[D4] mg/m^2 XXXXX 
- --- YYYY 
Grade X 
No 
XXXX 
[D4] mg/m^2 Other, XXXXX 
DDMMMYYYY (XXX) 
Grade X 
Yes 
Liver/ Other, XXXXX 
XXXX 
[D4] mg/m^2 XXXXX 
- --- YYYY 
Grade X 
Yes 
Lungs 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 90 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
Listing 16.2.4-4.1 - Prior Cancer Therapies 
(Safety Population) - Dose Escalation 
 
 
Center/ 
Patient 
CPX-POM 
Dose group 
Therapy 
Type 
Therapy 
Name 
Line of 
Therapy 
Treatment 
Setting 
Treatment 
Intent 
Start Date (Day)/ 
End Date (Day) 
Best 
Response 
Reason for 
discontinuation 
XXXX 
30 mg/m^2 
XXXXX 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX)/ 
DDMMMYYYY(XX) 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 XXXXX 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX)/ 
DDMMMYYYY(XX) 
XXXXX 
XXXXX 
XXXX 
[D3] mg/m^2 Radiation, 
XXXXX 
X 
XXXXX 
XXXXX 
DDMMMYYYY(XX)/ 
XXXXX 
XXXXX 
XXXXX 
DDMMMYYYY(XX) 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 91 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Listing 16.2.4-5.1 - Medical History and Concomitant Disease 
(Safety Population) - Dose Escalation 
 
CPX-POM Dose Group: 30 mg/m^2 
 
 
System Organ Class/ 
 
Any medication/non- 
drug therapies 
currently being 
Center/ 
Patient 
Preferred Term/ 
Verbatim 
Start Date (Day)  End Date (Day) 
taken for this 
condition? 
 
 
XXXX 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
DDMMMYYYY (XXX) 
DDMMMYYYY (XXX) 
No 
 
XXXX 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
--MMMYYYY 
Ongoing 
Yes 
<cont.> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
MedDRA <version no.> 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 92 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Listing 16.2.4-5.2 - Medical History and Concomitant Disease 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-5.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 93 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.4-6.1 - Cardiac Function 
(Safety Population) - Dose Escalation 
 
Echocardiogra 
Left 
ventricula 
Center/P 
CPX-POM 
m or MUGA 
Scan 
Method of 
Date of 
r ejection 
fraction 
Overall 
Interpretatio 
If Clinically 
Significant, 
atient 
Dose group 
Visit 
performed? 
Assessment 
Assessment (%) 
n 
specify 
XXXX 
30 mg/m^2 
C1 TRT D1 
Yes 
Echocardiogra 
m 
DDMMMYYYY 
XX 
XXXXX 
XXXX 
XXXX 
[D2] mg/m^2 
[D3] mg/m^2 
C1 TRT D1 
C1 TRT D1 
Yes 
Yes 
MUGA 
Echocardiogra 
m 
DDMMMYYYY 
DDMMMYYYY 
XX 
XX 
Abnormal CS 
XXXXX 
XXXXX 
<etc> 
 
NCS: Not Clinically Significant; CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
 
 
Listing 16.2.4-6.2 - Cardiac Function 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-6.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 94 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
Listing 16.2.4-7.1 - Ophthalmologic Exam 
(Safety Population) - Dose Escalation 
 
 
 
Center/ 
Patient 
 
CPX-POM 
Dose group 
Visit 
Ophthalmology 
Assessments 
performed? 
Assessment 
performed by a 
qualified 
Ophthalmologist? 
Use of 
Corrective 
Lenses? 
 
Date of 
Assessment 
 
Overall 
Interpretation 
 
If Abnormal CS, 
specify 
XXXX 
30 mg/m^2 
C1 TRT D1 
Yes 
Yes 
Yes 
DDMMMYYYY 
XXXXX 
XXXX 
[D2] mg/m^2  C1 TRT D1 
Yes 
No 
No 
DDMMMYYYY 
Abnormal CS 
XXXXX 
XXXX 
[D3] mg/m^2  C1 TRT D1 
Yes 
Yes 
No 
DDMMMYYYY 
XXXXX 
<etc> 
NCS: Not Clinically Significant; CS: Clinically Significant. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file 
name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 95 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
• 
Use abbreviations or codes to present data if not enough space (and add appropriate abbreviations / codes in footnotes). 
 
Listing 16.2.4-8.1.1 - Prior and Concomitant Medications 
CPX-POM Dose Group: 30 mg/m^2 
(Safety Population) - Dose Escalation 
Center/ 
Therapeutic Class 
Preferred Term 
Start Date (Day)/ 
Dose (unit)/ 
Frequency/ 
Prophylaxis?/ 
Patient 
Category 
Verbatim 
End Date (Day) 
Route 
Reason 
XXXX 
Prior 
Conc. 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
DDMMMYYYY (-180)/ 
DDMMMYYYY (XXX) 
--MMMYYYY/ 
Ongoing 
XXXXXXXX (XXX)/ 
Once/ 
Inhalation 
Other, XXXX/ 
bid/ 
Cutaneous 
Yes/ XXXXXXXXXXXX 
No/ XXXXXX 
XXXX 
Prior 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
--MMMYYYY/ 
DDMMMYYYY (XXX) 
200 mg/ 
tid/ 
Other, XXXXX 
Yes/ 
XXXXXXXXXXXXXXXXX 
X 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
Prior = any medication whose end date is before the date of first dose. 
Conc. = concomitant = any medication that started before the date of first dose and stopped on (or is ongoing after) the date of 
first dose OR any medication whose start date is either the same as (or after) the date of first dose. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 96 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.4-8.1.2 - Prior and Concomitant Medications 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-8.1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 97 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.4-8.2.2 - Chemotherapy 
(Safety Population) - Expansion 
 
 
 
Center/ 
Patient 
Name of 
Medication 
Start Date (Day)/ 
End Date (Day) 
Dose (unit)/ 
Route 
 
 
XXXX 
Gemcitabine 
DDMMMYYYY (XXX)/ 
DDMMMYYYY (XXX) 
Cisplatin 
--MMMYYYY/ 
Ongoing 
XXXXXXXX (XXX)/ 
XXXXXXXX 
XXXXXXXX (XXX)/ 
XXXXXXXX 
 
XXXX 
XXXXXXXX 
--MMMYYYY/ 
DDMMMYYYY (XXX) 
XXXXXXXX (XXX)/ 
XXXXXXXX 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
Only patients from Chemotherapy eligible group are included in this listing. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 98 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE --- 
Page 1 of X 
 
 
Listing 16.2.4-9.1 - Surgeries and Procedures 
(Safety Population) - Dose Escalation 
 
CPX-POM Dose Group: 30 mg/m^2 
 
System Organ Class/ 
Center/ 
Patient 
Preferred Term/ 
Verbatim 
Start Date (Day) 
 
 
XXXX 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
DDMMMYYYY (XXX) 
 
XXXX 
XXXXXX/ 
XXXXX/ 
XXXXXXXXXXX 
--MMMYYYY 
<cont.> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
MedDRA <version no.> 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 99 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Listing 16.2.4-9.2 - Surgeries and Procedures 
(Safety Population) - Expansion 
Replicate of Listing 16.2.4-9.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 100 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.5-1.1 - Treatment Administration 
(Safety Population) - Dose Escalation 
CPX-POM Dose 
Amount per 
Total Infusion 
Was Total 
Volume Infused?/ 
Administration 
Center/ 
CPX-POM 
Dose 
Protocol?/ If 
no, Reason for 
Bag Volume of 
Saline and CPX- 
If no, actual 
Volume Infused 
Date (Day) 
Infusion Start 
Arm Used 
Infusion 
Patient 
Visit 
group 
Adjustment? 
POM (ml) 
(ml)? 
Time- End Time 
for IV 
Interrupted? 
XXXXXXXX 
BAS 
30 mg/m^2 
Yes 
XXX 
Yes 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
C1 TRT 
D2 
30 mg/m^2 
Yes 
XXX 
Yes 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
C1 TRT 
D3 
30 mg/m^2 
Yes 
XXX 
Yes 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
C1 TRT 
D4 
30 mg/m^2 
Yes 
XXX 
Yes 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
 
C1 TRT 
D5 
30 mg/m^2 
No/ 
Adverse event 
XXX 
No/ 
XXX 
DDMMMYYYY (XX) 
HH:MM-HH:MM 
Right 
Yes [a] 
 
<repeat for Days 1,2,3,4 and 5 of next cycles if relevant> 
 
IV: Intravenous. 
[a] See further details regarding infusion interruption in Listing 16.2.5-2.1. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 101 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
• 
In footnote [a], replace ‘Listing 16.2.5-2.1’ by ‘Listing 16.2.5-2.2’. 
 
Listing 16.2.5-1.2 - Treatment Administration 
(Safety Population) - Expansion 
Replicate of Listing 16.2.5-1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 102 of 125 
 
 
reaction 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
• 
Include only patients with infusion interruption. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.5-2.1 - Infusion Interruption 
(Safety Population)- Dose Escalation 
 
 
 
Reason for 
Administration Date 
Time 
Reason 
Center/ 
CPX-POM 
Infusion 
(Day) Time Infusion Infusion 
Infusion 
for Not 
Infusion Site 
Patient 
Visit 
Dose group 
Interrupted? 
Interrupted 
Restarted? 
Restarted 
Restarting? 
Reaction? 
 
XXXXXXXX  C1 TRT D5 30 mg/m^2 
Infusion 
DDMMMYYYY (XX) 
HH:MM 
No 
Other, XXXXX 
Yes 
 
XXXXXXXX  C2 TRT D2 30 mg/m^2 
Other, XXXXX 
DDMMMYYYY (XX) 
HH:MM 
Yes 
HH:MM 
No 
<cont> 
 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Listing 16.2.5-2.2 - Infusion Interruption 
(All Patients Enrolled) - Expansion 
Replicate of Listing 16.2.5-2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 103 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.5-3.1 - Drug Exposure 
(Safety Population) - Dose Escalation 
 
Center/ 
Patient 
CPX-POM Dose 
group 
Date of 
first dose administration 
Visit of 
last dose 
administration 
Date of 
last dose 
administration 
Exposure 
(days) 
Exposure 
(mg) 
XXXX 
30 mg/m^2 
DDMMMYYYY 
C1 TRT D5 
DDMMMYYYY 
XX 
XX 
XXXX 
[D2] mg/m^2 
DDMMMYYYY 
C2 TRT D5 
DDMMMYYYY 
XX 
XX 
<cont.> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. 
The CPX-POM exposure expressed in days is defined as: (last dose taken date - first dose taken date +1) + 16 days. 
The CPX-POM exposure expressed in mg is defined as: sum of all (dose per m^2 x Body Surface Area), using Body Surface Area 
calculated at baseline for Cycle 1 and Cycle 2 dose administrations, and calculated on Day 1 of every other treatment cycle 
from Cycle 3 dose administration. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
Listing 16.2.5-3.2 - Drug Exposure 
(Safety Population) - Expansion 
Replicate of Listing 16.2.5-3.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 104 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
 
Listing 16.2.6-1.1 - RECIST Target Lesions 
(Efficacy Population) - Dose Escalation 
 
Center/ 
Patient 
CPX-POM 
Dose group 
Visit/ 
Target Lesions 
Identified at 
Screening Visit? 
Date of 
Scans 
review 
Lesion 
Number 
Organ 
Site 
Specific 
Location 
within the 
Organ Site 
Lymph 
Node 
Type 
Method 
Lesion 
Diameter 
(mm) 
Split or 
coalesced? 
XXXX 
30 mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
T02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C2 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
DDMMMYYYY 
T02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C2 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C3 TRT D1 / Yes 
DDMMMYYYY 
T01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
<etc> 
 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 105 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Listing 16.2.6-2.1 - RECIST Non-Target Lesions 
(Efficacy Population) - Dose Escalation 
 
 
Center/ 
Patient 
CPX-POM 
Dose 
group 
Visit/ 
Non-Target Lesions 
Identified at Screening 
Visit? 
Date of Scans review 
Lesion 
Number 
Organ 
Site 
Specific 
Location 
within the 
Organ Site 
Lymph 
Node 
Type 
Method 
XXXX 
30 mg/m^2 
C1 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
NT02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] 
mg/m^2 
C1 
C2 
TRT 
TRT 
D1 
D1 
/ 
/ 
Yes 
Yes 
DDMMMYYYY 
DDMMMYYYY 
NT01 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
NT02 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
NT03 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] 
mg/m^2 
C1 
C2 
TRT 
TRT 
D1 
D1 
/ 
/ 
Yes 
Yes 
DDMMMYYYY 
DDMMMYYYY 
NT01 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C3 TRT D1 / Yes 
DDMMMYYYY 
NT01 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
<etc> 
 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 106 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.6-3.1 - RECIST response 
(Efficacy Population) - Dose Escalation 
Center/ CPX-POM 
Sum of 
Target Lesion 
Non-Target Lesion 
Unequivocal Overall 
Patient Dose group 
Visit 
diameters (mm) 
Response 
Response 
new lesions Response 
XXXX 
30 mg/m^2 
C1 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 C1 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C2 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
XXXX 
[D2] mg/m^2 C1 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C2 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
C3 TRT D1 
DDMMMYYYY 
XXXXX 
XXXXX 
XXXXX 
XXXXX 
<etc> 
 
CR = Complete response; PR = Partial response; SD = Stable disease; PD = Progressive disease; NE = Not evaluable. 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 107 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing CPX-POM dose. 
 
Listing 16.2.6-4.1 - Tumor Marker 
(Efficacy Population) - Dose Escalation 
Center/ CPX-POM 
Tumor marker 
assessment 
Date of 
Type of 
If other, 
Patient Dose group 
Visit 
performed? 
assessment 
sample 
Tumor marker 
specify 
Result 
Unit 
XXXX 
30 mg/m^2 
C1 TRT D1 
Yes 
DDMMMYYYY 
XXXXX 
XXXXX 
XX.X 
XXX 
XXXXX 
XXXXX 
XX.X 
XXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 
Yes 
DDMMMYYYY 
XXXXX 
XXXXX 
XX.X 
XXX 
C2 TRT D1 
Yes 
DDMMMYYYY 
XXXXX 
XXXXX 
XX.X 
XXX 
XXXX 
[D2] mg/m^2 
C1 TRT D1 
Yes 
DDMMMYYYY 
XXXXX 
Other 
XXXXX 
XX.X 
XXX 
C2 TRT D1 
No 
C3 TRT D1 
Yes 
DDMMMYYYY 
XXXXX 
XXXXX 
XX.X 
XXX 
<etc> 
 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 108 of 125 
 
 
 
Listing 16.2.6-5.2 - Evaluable TURBT Results 
(Efficacy Population) - Expansion 
 
TURBT 
performed 
Tumor tissue 
sample 
Tumor 
tissue 
Highest 
Pathological 
within 8 
obtained 
sample 
Viable 
confirmation 
Archived 
weeks prior 
Initial 
from a 
obtained 
Tumor 
of Muscularis 
tumor 
Center/ 
to cycle 1 
or repeat 
Date of 
referring 
from 
content in 
Propria 
tissue from 
Patient Group 
Day 1? 
TURBT 
procedure 
institution? 
TURBT? 
TURBT (%) 
Invasion? 
TURBT used? 
XXXX 
Cisplatin 
ineligible 
Yes 
Initial 
DDMMMYYYY 
Yes 
Yes 
XX 
Yes 
Yes 
XXXX 
Chemotherapy 
eligible 
Yes 
Repeat 
DDMMMYYYY 
Yes 
No 
Yes 
Yes 
XXXX 
Cisplatin 
ineligible 
No 
 
 
 
<etc> 
 
TURBT = Transurethral resection of bladder tumour. 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 109 of 125 
 
 
 
Listing 16.2.6-6.2 - Radical Cystectomy 
(Efficacy Population) - Expansion 
 
 
Center/ 
Patient Group 
Formalin-fixed, paraffin- 
embedded bladder tumor tissue 
obtained at time of RC 
Date of procedure 
Tumor tissue sample 
obtained from cystectomy 
used? 
Highest Viable Tumor 
content from 
cystectomy (%) 
Cisplatin 
ineligible 
Yes 
DDMMMYYYY 
Yes 
XX 
XXXX 
Chemotherapy 
eligible 
Yes 
DDMMMYYYY 
No 
XXXX 
Cisplatin 
ineligible 
Yes 
 
 
 
<etc> 
 
RC = Radical cystectomy. 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
XXXX 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 110 of 125 
 
 
 
Listing 16.2.6-7.2 - Determination of Recurrence and Survival 
(Efficacy Population) - Expansion 
 
 
 
 
 
Center/ 
Patient Group 
Attend any 
follow-up 
visits 
(includes 
phone 
calls)? 
 
 
 
If no, 
reason 
 
 
 
Date of 
Death 
 
 
 
Cause of 
Death 
 
 
Physician 
Decision, 
specify 
 
 
 
Other, 
specify 
 
 
Date of 
study 
completion 
 
 
Date of last 
contact with 
patient 
Cisplatin 
ineligible 
No 
Death 
DDMMMYYYY 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
XXXX 
Chemotherapy 
eligible 
Yes 
DDMMMYYYY 
DDMMMYYYY 
 
XXXX 
Cisplatin 
ineligible 
No 
Physician 
Decision 
XXXXXX 
DDMMMYYYY 
DDMMMYYYY 
 
XXXX 
Cisplatin 
No 
ineligible 
 
DDMMMYYYY 
DDMMMYYYY 
 
 
 
<etc> 
 
Dates are displayed as DDMMMYYYY, -- represents an unknown date component. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
XXXX 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 111 of 125 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.6-8.2 - Recurrence-Free Survival and Overall Survival 
(Efficacy Population) - Expansion 
 
 
 
 
Center/ 
Patient Group 
Date of 
first CPX- 
POM 
Infusion 
(Day) 
 
 
Date of 
Recurrence 
(Day) 
 
 
Date of 
Death 
(Day) 
 
Start Date of 
First Further 
Anti-cancer 
Therapy (Day) 
 
Date of 
Last 
Contact 
(Day) 
 
 
 
RFS 
(month) 
 
 
Censoring 
/ Event 
for RFS 
 
 
 
OS 
(month) 
 
 
Censoring/ 
Event for 
OS 
Cisplatin 
ineligible 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
XX.X 
(XX) 
Event 
XX.X 
Event 
 
XXXX 
Chemotherapy 
eligible 
 
 
XXXX 
Cisplatin 
ineligible 
 
XXXX 
Cisplatin 
ineligible 
DDMMMYYYY 
(XX) 
 
 
DDMMMYYYY 
(XX) 
 
DDMMMYYYY 
(XX) 
 
DDMMMYYYY 
(XX) 
 
 
DDMMMYYYY 
(XX) 
 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
(XX) 
 
 
DDMMMYYYY 
(XX) 
 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
(XX) 
DDMMMYYYY 
(XX) 
 
 
DDMMMYYYY 
(XX) 
 
DDMMMYYYY 
(XX) 
 
XX.X 
Censoring 
XX.X 
Event 
 
 
XX.X 
Event 
XX.X 
Event 
XX.X 
Censoring 
XX.X 
Censoring 
 
 
 
<etc> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
RFS = Recurrence Free Survival, OS = Overall Survival. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
XXXX 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 112 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where DLT= Yes. 
 
 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.7-1.1 - Dose-Limiting Toxicity 
CPX-POM Dose Group: 30 mg/m^2 
(Safety Population) - Dose Escalation 
Center/ 
System Organ Class/ 
Preferred Term/ 
Start Date (Day)/ 
Action Taken/ 
Medication or 
Outcome/ 
Grade/ 
Patient 
Verbatim 
End Date (Day) 
Therapies Taken? 
Relationship 
SAE? 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
DDMMMYYYY (XXX) 
None/ 
No 
XXXXXXXX/ 
Grade 1/ 
Not related 
No 
XXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
Ongoing 
Dose Adjusted/ 
Yes 
Resolved/ 
Grade 3/ 
Definitely related 
Yes 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
DDMMMYYYY (XXX)/ 
--MMMYYYY 
XXXXXXXX/ 
XXXXXX/ 
XXXXXXX 
No 
<cont.> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown date 
component. 
MedDRA version <version #>. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 113 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where SAE = Yes. 
• 
Remove column ‘SAE’. 
 
Listing 16.2.7-2.1 - Adverse Events 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.7-1.1 
 
 
 
Listing 16.2.7-2.2 - Adverse Events 
(Safety Population) - Expansion 
Replicate of Listing 16.2.7-2.1 
 
 
 
 
 
Listing 16.2.7-3.1 - Serious Adverse Events 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.7-1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 114 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where action taken = Drug Withdrawn. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.7-3.2 - Serious Adverse Events 
(Safety Population) - Expansion 
Replicate of Listing 16.2.7-3.1 
 
 
 
 
 
Listing 16.2.7-4.1 - Adverse Events Leading to Discontinuation 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.7-1.1 
 
 
 
 
 
Listing 16.2.7-4.2 - Adverse Events Leading to Discontinuation 
(Safety Population) - Expansion 
Replicate of Listing 16.2.7-4.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 115 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
• 
Select all AEs where outcome = Fatal 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
 
Listing 16.2.7-5.1 - Adverse Events Leading to Death 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.7-1.1 
 
 
 
 
 
Listing 16.2.7-5.2 - Adverse Events Leading to Death 
(Safety Population) - Expansion 
Replicate of Listing 16.2.7-5.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 116 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
 
Listing 16.2.8-1.1 - Patients Laboratory Profile: Hematology 
(Safety Population) - Dose Escalation 
 
CPX-POM Dose Group: 30 mg/m^2 
Center/ 
Patient Visit 
 Assessment  
Date 
Time 
Study 
Day 
Parameter 
(Unit) 
Normal 
Range 
Result 
CTCAE 
grade 
Change 
from 
Baseline 
CS? 
XXXX 
BAS 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
Grade 1 
C1 TRT D1 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX L/H 
Grade 2 
XXXX 
C1 TRT D4 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX L/H 
Grade 2 
XXXX 
C1 TRT D10 DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX L/H 
Grade 3 
XXXX 
CS 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit and Day 4 visit if relevant> 
<for the last cycle, repeat also for Day 22 visit and Day 28 visit> 
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. 
Baseline was the last non-missing assessment prior or on the first dose date. 
SI units and results presented. L/H = low/high value based upon normal ranges. 
R = repeat/unscheduled assessments. CS = Clinically Significant; NCS = Not Clinically Significant; ND = Not Done. 
Laboratory ranges are based on NCI-CTCAE version 4.03. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 117 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing order. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.8-1.2 - Patients Laboratory Profile: Hematology 
(Safety Population) - Expansion 
Replicate of Listing 16.2.8-1.1 
 
 
 
 
 
Listing 16.2.8-2.1 - Patients Laboratory Profile: Clinical Chemistry 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.8-1.1 
 
 
 
 
 
 
Listing 16.2.8-2.2 - Patients Laboratory Profile: Clinical Chemistry 
(Safety Population) - Expansion 
Replicate of Listing 16.2.8-2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 118 of 125 
 
 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing order. 
• 
Only Day 1 of each cycle. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
PROGRAMMING NOTES: 
• 
Listing to be sorted by increasing order. 
• 
Only Day 1 of each cycle. 
• 
Remove CTCAE column and footnote. 
 
Listing 16.2.8-3.1 - Patients Laboratory Profile: Coagulation 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.8-1.1 
 
 
 
 
Listing 16.2.8-3.2 - Patients Laboratory Profile: Coagulation 
(Safety Population) - Expansion 
Replicate of Listing 16.2.8-3.1 
 
 
 
 
 
 
Listing 16.2.8-4.1 - Patients Laboratory Profile: Thyroid Panel 
(Safety Population) - Dose Escalation 
Replicate of Listing 16.2.8-1.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 119 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.8-4.2 - Patients Laboratory Profile: Thyroid Panel 
(Safety Population) - Expansion 
Replicate of Listing 16.2.8-4.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 120 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for the other CPX-POM doses by increasing order. 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
Listing 16.2.8-5.1 - Patients Laboratory Profile: Urinalysis 
CPX-POM Dose Group: 30 mg/m^2 
(Safety Population) - Dose Escalation 
Center/ 
Patient Visit 
 Assessment  
Date 
Time 
Study 
Day 
Parameter 
Normal 
(Unit) 
Range 
Result 
CS? 
XXXX 
BAS 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
C1 TRT D1 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
C1 TRT D4 
DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
C1 TRT D10 DDMMMYYYY HH:MM XXX 
XXXXXXXX (XXXX) 
XXXXXX 
XX 
CS 
 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit and Day 4 visit if relevant> 
<for the last cycle, repeat also for Day 22 visit and Day 28 visit> 
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY, -- represents an unknown 
date component. 
Baseline was the last non-missing assessment prior or on the first dose date. 
R = repeat/unscheduled assessments. CS = Clinically Significant; NCS = Not Clinically Significant; ND = Not Done. 
 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 
 
 
 
Listing 16.2.8-5.2 - Patients Laboratory Profile: Urinalysis 
(Safety Population) - Expansion 
Replicate of Listing 16.2.8-5.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
Page 121 of 125 
 
 
 
Listing 16.2.9-1.1 - Vital Signs 
(Safety Population) - Dose Escalation 
 
 CPX-POM Dose Group: 30 mg/m^2 
 
 
Center/ 
Patient 
Visit 
 Assessment  
Date 
Time 
Study 
Day 
Timepoint 
Parameter (unit) 
Result 
Change from Baseline 
XXXX 
BAS 
DDMMMYYYY HH:MM 
XXX 
Pulse Rate (bpm) 
XXX L 
Respiratory Rate (bpm) 
XXX 
Systolic BP (mmHg) 
XXX 
Diastolic BP (mmHg) 
XXX 
Oxygen Saturation (%) 
Body Weight (kg) 
Temperature (C) 
XXX 
XXX.X 
XX.X 
 
C1 TRT D1 
DDMMMYYYY HH:MM 
XXX 
6 hours 
Post Dose 
Pulse Rate (bpm) 
XXX H 
XX 
Respiratory Rate (bpm) 
XXX 
XX 
Systolic BP (mmHg) 
Diastolic BP (mmHg) 
Oxygen Saturation (mmHg) 
XXX 
XXX 
XXX 
VH 
XX 
XX 
XX 
Body Weight (kg) 
XXX.X 
X.X 
Temperature (C) 
XX.X 
X.X 
 
<repeat for Day 3, Day 4, Day 5, Day 6 and Day 10 visits of Cycle 1> 
<for Cycle 2 to last-1 cycle, repeat from Day 1 to Day 6 visits if relevant> 
<for the last cycle, repeat also for Day 22 visit and Day 28 follow-up visit> 
 
Study Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. Baseline was the last 
non-missing assessment prior or on the first dose. 
L = Low; H = High; VH = Very High; BP = Blood Pressure; bpm = beats per minute; ND = Not Done. 
Pulse Rate: L: <55 bpm; H: 101-150 bpm; VH: >150 bpm. 
Systolic BP: L: <95 mmHg; H: 131-160 mmHg; VH: >=161 mmHg. 
Diastolic BP: L: <50 mmHg; H: 86-100 mmHg; VH: >=101 mmHg. 
R = repeated/ unscheduled assessment. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file name.rtf) 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 122 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
 
 
 
 
 
Listing 16.2.9-1.2 - Vital Signs 
(Safety Population) - Expansion 
Replicate of Listing 16.2.9-1.1 
 
PROGRAMMING NOTES: 
• 
Include all parameters: blood pressure, respiratory rate, pulse, oxygen saturation, temperature, BSA, BMI and height. 
• 
Repeat for all doses groups 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 123 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all dose groups. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.9-2.1 - ECG Results 
CPX-POM Dose Group: 30 mg/m^2 
(Safety Population) - Dose Escalation 
Center/ 
Patient 
Visit 
Assessment Date 
(Day) 
Parameter (unit) 
Result 
Change from baseline 
XXXX 
BAS 
DDMMMYYYY (XXX) 
Heart Rate (bpm) 
XXX 
XX 
PR interval (msec) 
XXX 
XX 
RR interval (msec) 
XXX 
XX 
QRS duration (msec) 
XXX 
XX 
QT interval (msec) 
XXX 
XX 
QTcF interval (msec) 
XXX 
XX 
Overall Interpretation 
Normal 
C1 TRT D5 DDMMMYYYY (XXX) 
Heart Rate (bpm) 
XXX ++ 
XX * 
PR interval (msec) 
XXX 
XX 
RR interval (msec) 
XXX 
XX 
QRS duration (msec) 
XXX 
XX 
QT interval (msec) 
XXX 
XX 
QTcF interval (msec) 
XXX + 
XX 
Overall Interpretation 
Abnormal, CS 
<for Cycle 2 to last-1 cycle, repeat for Day 1 visit if relevant> 
<for the last cycle, repeat also for Day 28 follow-up visit> 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. Baseline was the last non- 
missing assessment prior or on the first dose date. 
QTcF: +: >450 msec; ++: > 480 msec; +++: >500 msec; *: > 30 msec above baseline; **: > 60 msec above baseline. 
R = repeated/ unscheduled assessment. CS = Clinically significant; NCS = Not Clinically Significant. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file 
name.rtf) 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 124 of 125 
 
 
PROGRAMMING NOTES: 
• 
Change label from ‘CPX-POM Dose group’ to ‘Group’ and populate with ‘Cisplatin ineligible’/‘Chemotherapy eligible’. 
 
 
 
Listing 16.2.9-2.2 - ECG Results 
(Safety Population) - Expansion 
Replicate of Listing 16.2.9-2.1 
 


Sponsor: CicloMed 
Protocol: CPX-POM-001 
Statistical Analysis Plan (TFL shells): 
Version 2.0 / 03Nov2021 
Page 125 of 125 
 
 
PROGRAMMING NOTES: 
• 
Repeat for all dose groups. 
Protocol: CPX-POM-001 
Extract date: DDMMMYYYY 
--- DELIVERY TYPE ---- 
Page 1 of X 
 
Listing 16.2.9-3.1 - Digital Holter Monitoring 
(Safety Population) - Dose Escalation 
 
CPX-POM Dose Group: 30 mg/m^2 
 
Center/ 
  Assessment Start     Assessment End   Study 
Any Alert 
Alert Flag 
Patient 
Visit 
Date 
Time 
Date 
Time 
Day 
Flags? 
Timepoint 
Type 
Specify 
XXXX 
BAS 
DDMMMYYYY HH:MM 
DDMMMYYYY HH:MM 
xx 
Yes 
Pre-dose 
0.25 
> 60 ms 
increase from 
baseline 
Other 
(specify) 
xxxxx 
… 
 
 
Day was from the date of first dose of CPX-POM administration. Dates are displayed as DDMMMYYYY. Baseline was the last non- 
missing assessment prior or on the first dose date. 
Program: (Program name.sas) (run on: DDMMMYYYY HH:MM) 
Filename: (Specify file 
name.rtf) 
 


 
 
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