Clinical trial NCT03101358
Conditions: Cutaneous Metastasis
Keywords: cutaneous metastases cutaneous metastasis skin metastases skin metastasis
Sponsor: NanOlogy, LLC
Start date: 2018-01-31; Completion date: 2020-04-29
Enrollment: 23 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This study evaluates a topical nanoparticle paclitaxel ointment (SOR007) for the treatment of cutaneous metastases from non-melanoma cancer in adults. Three concentrations of SOR007 will be evaluated in dose-rising cohorts of three. An expanded cohort will treat additional subjects at the maximum tolerated dose.

Detailed description:
This is a Phase 1/2, open-label, dose-rising study evaluating the safety, tolerability and preliminary efficacy of three concentrations of SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (0.15%, 1.0%, and 2.0%) applied to non-melanoma cutaneous metastases. A treatment area of 50 cm2 will be selected by the Investigator. Using a gloved hand, subjects will apply one Finger Tip Unit (FTU) of SOR007 to the 50 cm2 treatment area twice daily at approximately the same time each day for 28 days, with the option of extending treatment an additional 28 days to total 56 days for subjects in the dose expansion phase. At each visit (Days 1, 8, 15, 29, and 43 for 28 treatment days; Days 8, 15, 29, 57, and 70 for 56 treatment days), at least two global and two close-up color photographs of the treatment area will be taken (with a ruler for scale). The photographs will be analyzed with ImageJ. Eligible lesions will be determined at baseline by the RECIST definition of measurable tumors (≥ 10mm in its longest diameter). The study will include a dose escalation phase and a dose expansion phase.

In the dose escalation phase, formal safety reviews will be conducted after the last subject in each cohort of three subjects completes 15 days of treatment. The next dose level will enroll upon a finding of safety and tolerability. The top dose or the maximum tolerated dose (if DLT occurs) will be taken into the dose expansion phase and additional subjects will be enrolled to reach a maximum of 16 subjects at that dose.

Arms: arm 1: 0.15% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days arm 2: 1.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days arm 3: 2.0% SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment applied topically twice daily for 28 days or up to 56 days
Interventions: intervention 1: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment
Intervention descriptions: intervention 1: One (1) Finger Tip Unit (FTU), or approximately 0.5 g, of SOR007 ointment will be applied topically to a 50 cm2 treatment area.

Protocol documents:
Prot_000.pdf: 
Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of Topical SOR007 for Cutaneous Metastases 
Version: 7.0 
SOR007-2017-01 
 
US Biotest, Inc. 
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Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy 
Study of Topical SOR007 for Cutaneous Metastases 
 
Protocol Identifying Number:  
SOR007-2017-01 
 
Principal Investigator:  
Julie Eileen Lang, MD, FACS.  
University of Southern California 
1510 San Pablo Street, Suite 412 
Los Angeles, CA 90033 
 
IND Sponsor:  
 
 
 
NanOlogy, LLC 
231 Bonetti Drive, Suite 240 
San Luis Obispo, CA 93401-7310 
 
Version Number:   
 
 
7.0 
 
Date:  
 
 
 
 
28 December 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table of Contents 
LIST OF ABBREVIATIONS ....................................................................................................................................... 5 
SPONSOR SIGNATURE PAGE ............................................................................................................................... 7 
STATEMENT OF COMPLIANCE ............................................................................................................................. 8 
PROTOCOL SUMMARY ........................................................................................................................................... 9 
SCHEMATIC OF STUDY DESIGN ........................................................................................................................ 12 
1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................... 13 
1.1 
Background Information .................................................................................................................... 13 
1.2 
Rationale ............................................................................................................................................. 15 
1.3 
Potential Risks and Benefits ............................................................................................................ 16 
1.3.1 
Known Potential Risks ................................................................................................... 16 
1.3.2 
Known Potential Benefits .............................................................................................. 16 
2 
OBJECTIVES AND PURPOSE .................................................................................................................. 17 
3 
STUDY DESIGN AND ENDPOINTS ......................................................................................................... 17 
3.1 
Description of the Study Design ...................................................................................................... 17 
3.2 
Primary Endpoint ............................................................................................................................... 18 
3.3 
Secondary Endpoints ........................................................................................................................ 18 
3.4 
Exploratory Endpoints ....................................................................................................................... 19 
4 
STUDY ENROLLMENT AND WITHDRAWAL ......................................................................................... 19 
4.1 
Participant Inclusion Criteria ............................................................................................................ 19 
4.2 
Participant Exclusion Criteria ........................................................................................................... 20 
4.3 
Strategies for Recruitment and Retention ...................................................................................... 20 
4.4 
Participant Withdrawal or termination ............................................................................................. 21 
4.4.1 
Reasons for Withdrawal or Termination ..................................................................... 21 
4.4.2 
Handling of Participant Withdrawals or Termination ................................................. 21 
4.5 
Premature Termination or Suspension of Study ........................................................................... 22 
5 
STUDY DRUG .............................................................................................................................................. 22 
5.1 
Study Drug(s) Description ................................................................................................................ 22 
5.1.1 
Acquisition ....................................................................................................................... 22 
5.1.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 23 
5.1.3 
Product Storage and Stability ....................................................................................... 23 
5.1.4 
Preparation ...................................................................................................................... 23 
5.1.5 
Dosing and Administration ............................................................................................ 23 
5.1.6 
Route of Administration ................................................................................................. 24 
5.1.7 
Dosing and Dose Escalation ........................................................................................ 24 
5.1.8 
Dose Adjustments/Modifications/Delays .................................................................... 24 
5.1.9 
Duration of Treatment ................................................................................................... 24 
5.1.10 
Dosing Compliance ........................................................................................................ 24 
5.2 
Study Drug Accountability Procedures ........................................................................................... 25 
6 
STUDY PROCEDURES AND SCHEDULE .............................................................................................. 25 
6.1 
Study Procedures/Evaluations ......................................................................................................... 25 
6.1.1 
Study Specific Procedures ............................................................................................ 25 
6.1.2 
Standard of Care Study Procedures ........................................................................... 26 
6.2 
Treatment Area Selection ................................................................................................................. 27 
6.3 
Photographic Documentation........................................................................................................... 27 
6.4 
Laboratory Procedures/Evaluations ................................................................................................ 27 
6.4.1 
Clinical Laboratory Evaluations .................................................................................... 27 


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6.4.2 
Other Assays or Procedures ........................................................................................ 28 
6.5 
Study Schedule .................................................................................................................................. 28 
6.5.1 
Screening ........................................................................................................................ 28 
6.5.2 
Enrollment/Baseline ....................................................................................................... 29 
6.5.3 
Treatment ........................................................................................................................ 30 
6.5.4 
Follow up and End-of-Study Evaluations: Group A................................................... 33 
6.5.5 
Follow up and End-of-Study Evaluations: Group B................................................... 33 
6.5.6 
Early Termination Visit .................................................................................................. 34 
6.5.7 
UNSCHEDULED VISIT ................................................................................................. 34 
6.5.8 
Schedule of Events Table 1: Treatment Group A: 28 Days ..................................... 35 
6.5.9 
Schedule of Events Table 2: Treatment Group B: 56 Days ..................................... 37 
6.6 
Concomitant Medications, Treatments, and Procedures ............................................................. 39 
6.6.1 
Precautionary Medications, Treatments, and Procedures ....................................... 39 
6.6.2 
Prohibited Medications, Treatments, and Procedures ............................................. 39 
6.6.3 
Prophylactic Medications, Treatments, and Procedures .......................................... 39 
7 
ASSESSMENT OF SAFETY ...................................................................................................................... 40 
7.1 
Specification of Safety Parameters ................................................................................................. 40 
7.1.1 
Definition of Adverse Events (AE) and Adverse Drug Reaction (ADR) ................. 40 
7.1.2 
Definition of Serious Adverse Events (SAE) .............................................................. 40 
7.2 
Classification of an Adverse Event ................................................................................................. 41 
7.2.1 
Severity of Event ............................................................................................................ 41 
7.2.2 
Relationship to Study Agent ......................................................................................... 41 
7.2.3 
Expectedness ................................................................................................................. 42 
7.3 
Time Period and Frequency for Event Assessment and Follow-Up .......................................... 43 
7.4 
Reporting Procedures ....................................................................................................................... 43 
7.4.1 
Adverse Event Reporting .............................................................................................. 43 
7.4.2 
Serious Adverse Event Reporting ............................................................................... 44 
7.4.3 
Events of Special Interest ............................................................................................. 45 
7.4.4 
Reporting of Pregnancy ................................................................................................ 45 
7.5 
Study Halting Rules ........................................................................................................................... 45 
7.6 
Dose Escalation and Dose Limiting Toxicity .................................................................................. 46 
7.7 
Safety Oversight ................................................................................................................................ 48 
8 
CLINICAL MONITORING ............................................................................................................................ 48 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 49 
9.1 
Statistical and Analytical Plans ........................................................................................................ 49 
9.2 
Statistical Hypotheses ....................................................................................................................... 49 
9.3 
Analysis Datasets .............................................................................................................................. 49 
9.3.1 
Missing Data ................................................................................................................... 49 
9.4 
Description of Statistical Methods ................................................................................................... 49 
9.4.1 
General Approach .......................................................................................................... 49 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 49 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 49 
9.4.4 
Safety Analyses .............................................................................................................. 50 
9.4.5 
Adherence and Retention Analyses ............................................................................ 51 
9.4.6 
Baseline Descriptive Statistics ..................................................................................... 51 
9.4.7 
Planned Interim Analyses ............................................................................................. 51 


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9.4.8 
Multiple Comparison/Multiplicity................................................................................... 52 
9.4.9 
Tabulation of Individual Response Data ..................................................................... 52 
9.4.10 
Concomitant Medication................................................................................................ 52 
9.5 
Safety Monitoring Committee (SMC) .............................................................................................. 52 
9.6 
Sample Size ....................................................................................................................................... 52 
9.7 
Measures to Minimize Bias .............................................................................................................. 53 
9.7.1 
Enrollment/ Randomization/ Masking Procedures .................................................... 53 
9.7.2 
Evaluation of Success of Blinding ............................................................................... 53 
9.7.3 
Breaking the Study Blind/Participant Code ................................................................ 53 
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................... 53 
11 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................................. 54 
12 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 55 
12.1 
Ethical Standard ................................................................................................................................. 55 
12.2 
Institutional Review Board ................................................................................................................ 55 
12.3 
Informed Consent Process ............................................................................................................... 55 
12.3.1 
Consent and Other Informational Documents Provided to Participants ................ 55 
12.3.2 
Consent Procedures and Documentation .................................................................. 56 
12.4 
Study Subject and Data Confidentiality .......................................................................................... 57 
12.4.1 
Research Use of Stored Human Samples, Specimens or Data ............................. 57 
12.5 
Future Use of Stored Specimens .................................................................................................... 58 
13 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 58 
13.1 
Data Collection and Management Responsibilities ...................................................................... 58 
13.2 
Study Records Retention .................................................................................................................. 59 
13.3 
Protocol Deviations............................................................................................................................ 59 
13.4 
Publication and Data Sharing Policy ............................................................................................... 60 
14 
STUDY ADMINISTRATION ........................................................................................................................ 60 
14.1 
Study Leadership ............................................................................................................................... 60 
15 
CONFLICT OF INTEREST POLICY .......................................................................................................... 60 
16 
LIABILITY AND INSURANCE .................................................................................................................... 61 
17 
LITERATURE REFERENCES.................................................................................................................... 61 
 
 
 


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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
ALP 
alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate Aminotransferase 
BID 
‘Bis in Die’ or Twice per Day 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CNS 
Central Nervous System 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic Data Capture System 
eCRF 
Electronic Case Report Form 
FDA 
The U.S. Food and Drug Administration 
FTU 
Finger Tip Unit 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transferase 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
ICMJE 
International Committee of Medical Journal Editors 
IND 
Investigational New Drug Application 
IP 
Intraperitoneal 
IRB 
Institutional Review Board 
IV 
Intravenous 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
NDA 
New Drug Application 
NIH 
National Institutes of Health 
NRS-11 
Numeric Rating Scale 
NSCLC 
Non-Small Cell Lung Cancer 
PCA 
Precipitation with Compressed Antisolvents 
PK 
Pharmacokinetics 
PI 
Principal Investigator 
RBC 
Red Blood Cell 
RECIST 
Response Evaluation Criteria in Solid Tumours 


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SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SDLC 
Systems Development Life Cycle 
SMC 
Safety Monitoring Committee 
SOC 
Standard of Care 
TEAE 
Treatment-emergent Adverse Event 
USC 
University of Southern California 
USP/NF 
United States Pharmacopeia/National Formulary 
WBC 
White Blood Cell 
 
 




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STATEMENT OF COMPLIANCE 
I have read the attached protocol (SOR007-2017-01) Phase 1/2 Dose-Rising, Safety, Tolerability, 
and Efficacy Study of Topical SOR007 for Cutaneous Metastases, Version 7.0 dated 28 December 
2018 and agree to comply with the contents of this document. 
I agree to comply with applicable FDA regulations and guidelines set forth in 21 CFR Parts 11, 
50, 54, 56, and 312. 
This document is a confidential communication of US Biotest, Inc. The recipient agrees that no 
unpublished information contained herein will be published or disclosed without prior written 
permission of US Biotest, Inc. However, this document may be disclosed to appropriate 
institutional review boards, ethics review committees, or authorized representatives of the 
Investigator or of boards of health under the condition that they are requested to respect the 
confidentiality of the document. 
The signature of the Principal Investigator below constitutes his/her agreement. 
 
 
__________________________________________ 
__________________________ 
Signature of Principal Investigator 
 
 
 
Date 
 
 
__________________________________________ 
Printed Name of Principal Investigator 
 
 


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PROTOCOL SUMMARY 
Protocol #: 
SOR007-2017-01 
Title: 
Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of Topical 
SOR007 for Cutaneous Metastases. 
Summary: 
This is a Phase 1/2, open-label, dose-rising study evaluating the safety, 
tolerability and preliminary efficacy of three concentrations of SOR007 
(Uncoated Nanoparticle Paclitaxel) Ointment (0.15%, 1.0%, and 2.0%) 
applied topically twice daily for 28 days to non-melanoma cutaneous 
metastases, with the option of extending treatment an additional 28 days 
to total 56 days.  
Subjects will be screened and eligibility confirmed up to 14 days prior to 
treatment with SOR007. A treatment area of 50 cm2 containing at least one 
eligible lesion will be selected by the Investigator at baseline by the 
RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its 
longest diameter). Using a gloved hand, subjects will apply one Finger Tip 
Unit (FTU) of SOR007 to the 50 cm2 treatment area twice daily at 
approximately the same time each day for 28 to up to 56 days. Subjects 
will attend the clinic on Day 1 (Visit 2) for dose application training and 
observation of the first treatment application, returning 24 hours later for 
pharmacokinetic sample collection. Additional visits will be on Days 8, 
15, 29, and 43 for 28 treatment days, or on Days 8, 15, 29, 57 and 70 for 
56 treatment days. The final visit will be completed by phone or in the 
clinic (per Investigator determination), > 30 days after the last study drug 
dose to review adverse events. At each visit, at least two global and two 
close-up color photographs of the treatment area will be taken (with a ruler 
for scale) by the Investigator. The photographs will be uploaded from each 
visit to a secure, password protected Citrix ShareFile or site restricted-
access file, within 2 days of the visit. The Sponsor will then analyze lesion 
size using ImageJ. 
The study will include a dose escalation phase and a dose expansion phase.  
Dose Escalation Phase: 
During the dose escalation phase, the study will follow a standard 3+3 
dose-ascending design, with the first cohort of three subjects commencing 
treatment with 0.15% SOR007. A Safety Monitoring Committee (SMC) 
will review all available data after the last subject in each cohort of three 
subjects completes 15 days of treatment to determine whether dose 
escalation may continue. If a single dose limiting toxicity (DLT) is 


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identified in one of three subjects in the cohort, a further three subjects will 
be enrolled at the same dose level. If one or more DLT occur in the three 
additional subjects enrolled in the cohort, dose escalation will stop and the 
prior dose level will be regarded as the Maximum Tolerated Dose (MTD) 
and taken forward into the dose expansion phase. If no further DLT are 
identified, dose escalation will continue, until either a DLT is identified at 
a higher dose or the top dose of 2.0% SOR007 is reached. 
Dose Expansion Phase: 
In the dose expansion phase, additional subjects will be enrolled to reach 
a maximum of 16 total subjects at the MTD from the dose escalation phase. 
Subjects in the dose expansion phase will attend the clinic on the same 
visit days and receive the same evaluations as the dose escalation phase 
above. The option of 28 (Group A) or 56 (Group B) days of treatment will 
be per investigatior decision, dependent on subject disease progression, 
additional systemic chemotherapy or other metastatic treatment 
requirements. 
Objectives: 
 
Primary Objective: 
• To determine preliminary safety and tolerability of topical 
SOR007. 
Secondary Objectives: 
• To determine preliminary efficacy of topical SOR007;  
• To study potential reduction in pain at the treatment area; 
• To describe the pharmacokinetics of topical SOR007 Ointment 
applied to metastatic lesions. 
Endpoint 
Primary Outcome Measures: 
Safety and tolerability, as demonstrated by adverse events, changes in 
laboratory assessments, physical examination findings, and vital signs. 
Secondary Outcome Measures: 
Efficacy will be determined by the difference in the total area of eligible 
lesion(s) in the treatment area between baseline and Day 43 or 70 using a 
calibrated grid measurement system (ImageJ freeware) provided by the 
National Institutes of Health (NIH). Eligible lesions will be determined at 
baseline by the RECIST (Vn 1.1) definition of measurable tumors (≥ 
10mm in its longest diameter) (Eisenhauer 2009). 


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Objective Clinical Response (Complete Clinical Response (CR) + Partial 
Response (PR)) is defined as the percentage of patients who achieve 
complete clinical response or partial response 14 days after last treatment. 
Best overall response is defined as the best response recorded from the 
start of study treatment until the end of treatment.  
Reduction in pain at the treatment area will be measured by the Numeric 
Rating Scale (NRS-11) from baseline to Day 43 or 70. 
Systemic Exposure as determined by: Tmax, Cmax, AUC 
Pharmacokinetics 
(PK) 
Blood samples will be collected to analyze pharmacokinetic activity. 
Samples will be collected at 24 hours (+/- 2 hours) after the first study 
drug application.  
28 Days of Treatment: At Visits 3 and 4 (prior to the first daily 
application) and at Visits 5 and 6 (at any time during the visit). 
56 Days of Treatment: At Visits 3, 4 and 5 (prior to the first daily 
application) and at Visits 6 and 7 (at any time during the visit).  
Population: 
A minimum of three up to a maximum of 28 male and female subjects, ≥ 
18 years of age, with non-melanoma cutaneous metastases. 
Phase: 
1/2 
Number of Sites: 
Up to four 
Description of 
Study Agent: 
SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (SOR007) at 
concentrations of 0.15%, 1.0%, and 2.0%.  
Study Duration: 
The study duration is estimated to take 15 months, from start of enrollment 
to the last subject’s last visit. 
Participant 
Duration: 
Individual subject participation is estimated to be 75 or 102 days, including 
the screening period. 
 
 
 


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SCHEMATIC OF STUDY DESIGN 
Figure 1. Dose Escalation Algorithm – Flow Chart 
 


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1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE  
1.1 
Background Information  
The Sponsor, NanOlogy, LLC, has transferred responsibility for all obligations set forth in 21 
CFR Part 312 to US Biotest, Inc., with regard to IND 135896; in accordance with 21 CFR Part 
312, US Biotest, Inc., shall be considered the sponsor with regard to all activities related to the 
IND. 
Name and Description of Study Agent. 
Investigational drug product SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment (SOR007) is 
being developed for the topical treatment of cutaneous metastases. SOR007 consists of Uncoated 
Nanoparticle Paclitaxel suspended in an ointment vehicle. All excipients are compendial grade 
(USP/NF) and approved for topical route of administration at concentrations equal to or less than 
the Maximum Potency detailed in the FDA Inactive Ingredients Database. 
SOR007 is also being investigated under IND 126915 for the treatment of moderate to severe 
plaque psoriasis and actinic keratosis (Sponsor: DFB Soria, LLC). NanoPac® (sterile 
nanoparticulate paclitaxel) Powder for Suspension (“NanoPac”) contains the same nanoparticulate 
paclitaxel as SOR007, although the nanoparticulate paclitaxel in NanoPac is sterile (Sponsor: 
NanOlogy, LLC). NanoPac is being developed for the treatment of peritoneal malignancies under 
IND 073529, the treatment of pancreatic neoplasms under IND 132692, and the treatment of 
adenocarcinoma of the prostate under IND 132694.  
Non-clinical Summary 
Key findings of nonclinical studies with nanoparticulate paclitaxel include:  
• In vitro dermal penetration studies using human cadaver skin and the Franz diffusion cell 
system were conducted with prototype gel and ointment formulations of Uncoated 
Nanoparticle Paclitaxel to evaluate the rate and extent of in vitro dermal and transdermal 
delivery of paclitaxel. In the first study, three 1% Uncoated Nanoparticle Paclitaxel gels 
(designated as DowF1 through DowF3) and four 1% Uncoated Nanoparticle Paclitaxel 
ointments (designated as DowF4 through DowF7) were evaluated. In the second study, one 
0.5% (designated as DowF8), four 1% (designated as DowF10 through DowF13), and one 
2% (designated as DowF9) Uncoated Nanoparticle Paclitaxel ointments were tested, along 
with a second lot of 1% Uncoated Nanoparticle Paclitaxel ointment (designated DowF6 
formulation). There was negligible transdermal flux of paclitaxel in the first or second 
study. In the first study, DowF6 (1% SOR007 Ointment) demonstrated the highest total 
epidermal/dermal delivery (2.2% of the applied dose). In the second study, DowF8 (0.5% 
SOR007 Ointment) delivered 4.5% of the applied dose to the epidermis and dermis. 
 


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• Paclitaxel toxicokinetics were determined on Days 1 and 28 following once-daily topical 
administration of 0% (0 mg/kg/day) 0.3% (4.9 mg/kg/day), 1% (16.5 mg/kg/day) or 3% 
(49.9 mg/kg/day) SOR007 to the dorsum of 6 Göttingen minipigs/sex/group. Sex 
differences in paclitaxel mean Cmax and AUC0-24 values were generally less than 2-fold; 
therefore, results and discussions were based on combined-sex data. Exposure to paclitaxel 
increased with increasing SOR007 dose; however, the increases in mean Cmax and AUC0-
24 values were less than dose proportional. There were no observed adverse effects at the 
highest dose, 49.9 mg/kg/day, with an associated combined-sex Cmax of 12.5 ng/mL and an 
AUC (0-24) of 149 ng•hr/mL. Significant paclitaxel accumulation was noted following 
repeated-once daily topical application for 28 days. 
• A single-dose, GLP intraperitoneal (IP) toxicity study in the rat, conducted under IND 
073529, compared nanoparticulate paclitaxel dosed to the maximum tolerated dose (MTD) 
versus Taxol® dosed to the MTD. Results of this study indicated that the toxicity 
associated with IP administration of nanoparticulate paclitaxel is less than that associated 
with IP Taxol administration. 
• Subcutaneous administration of a single dose (20 mg/kg) of nanoparticulate paclitaxel in 
a non-GLP study in male rats resulted in no evidence of ulceration, irritation or other 
drug-related toxicity. 
Clinical Summary 
SOR007 has not been administered to humans for topical treatment of cutaneous metastases. A 
Phase 1 clinical trial of SOR007 for the indication of moderate to severe plaque psoriasis was 
completed under IND 126915 (Protocol SOR007-2016-01). Thirteen subjects with chronic plaque 
type psoriasis received occlusive application of six topical formulations:  SOR007 at 0.15%, 0.3%, 
1.0%, and 2.0%, vehicle, and an active comparator approximately daily for up to 10 treatments 
over a 12-day period.  Approximately 200 µL of each formulation was be applied on each dosing 
day. The total body surface area exposed to SOR007 was 4.52 cm2, or 0.03% total body surface 
area of a 1.6 m2 human. The daily dose was approximately 5.7 mg per day, for a total of 
approximately 57 mg of Uncoated Nanoparticle Paclitaxel per subject. Calculated on a mg/kg or 
mg/m2 basis, the paclitaxel applied topically over the 12-day study would be approximately 0.1 
mg/kg (3.8 mg/m2) per day, or 1.0 mg/kg (38 mg/m2) total exposure for a 60-kg subject. The 
primary endpoint was the change from baseline in psoriatic skin thickness (assessed by 
measurement of the thickness of the echolucent band (ELB) of the psoriatic infiltrate using 22 
MHz sonography). Clinical assessment, photo documentation, and PK analysis were also 
performed.  No treatment related AEs were reported by the subjects who had up to 10 daily topical 
applications of SOR007. There were no reports of local skin reactions seen under the hydrocolloid 
dressing during the 12-day study period. 
Twelve subjects completed the trial and were available for PK analysis. Blood was drawn on Day 
11 prior to dosing and then again at 1, 4, 8 and 24 hours after dosing. Following topical application 


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of ~5.7 mg daily dose (57 mg cumulative dose) of SOR007, Day 11 plasma paclitaxel 
concentrations over the 24-hr sampling interval were below the limit of quantitation (LLOQ of 10 
pg/mL) for 59 of the 60 samples tested.  Paclitaxel was quantifiable only in the 1-hour PK sample 
from a single subject, and this level (17.7 pg/mL) was near the lower limit of quantitation.  Thus, 
paclitaxel systemic exposure was negligible in psoriatic patients concomitantly receiving 200 µL 
each of the 0.15, 0.3, 1, and 2% SOR007 ointment formulations. 
1.2 
Rationale  
Cutaneous metastases occur in up to 10% of cancer patients (excluding melanoma) (Spratt 2014; 
Alcaraz 2014). Cutaneous metastases can cause considerable morbidity, leading to infection, 
bleeding, disfigurement and pain. The negative impacts to quality of life (QOL) for this population 
with advanced disease can be devastating (Spratt 2014). 
Despite the prevalence and impact of cutaneous metastases, a standard of care remains elusive. 
Treatment is complicated by underlying disease, poor patient performance, previous radiation 
therapy and short duration of overall survival. These factors make surgery and radiation unfeasible 
in most patients (Sideras 2008; Campana 2016; Cabula 2015). Systemic chemotherapy has 
negligible impact on most cutaneous metastases (Fernandez-Anton Martinez 2013; Spratt 2014). 
Additional therapies for cutaneous metastases include electrochemotherapy (ECT), photodynamic 
therapy (PDT), intralesional therapy (ILT), and topical therapy (TT). In a meta-analysis of 47 
prospective studies of 4,313 cutaneous metastases, the objective response rate to the therapies 
(including radiotherapy) was 60.2% (Spratt 2014). ECT demonstrated the best response rate 
(complete response rate 47.5%); however, ECT is an inpatient procedure requiring general 
anesthesia and often results in notable pain and dermatologic toxicity (inflammation, 
hyperpigmentation, and ulceration) (Cabula 2015). The less invasive alternatives, such as 
intralesional therapy and topical therapy demonstrate reduced efficacy in comparison to ECT. 
When effective reduction of cutaneous metastases cannot be achieved, as is often the case, 
healthcare providers must fall back on palliative wound care remedies (Fernandez-Anton Martinez 
2013). There is therefore a significant unmet need for an effective, less invasive alternative therapy 
for cutaneous metastases in patients already struggling with significant morbidity from the 
symptoms of and treatments for advanced primary cancer. 
Paclitaxel, formulated as Taxol or Abraxane, is approved by FDA for several cancers known to 
cause skin metastases, including ovarian cancer, breast cancer, non-small cell lung cancer, and 
pancreatic cancer (Taxol Package Insert, Abraxane Package Insert). Paclitaxel has also been used 
off-label with some effect in numerous other cancers, including bladder cancer, cervical cancer, 
endometrial cancer, esophageal cancer, squamous cell carcinoma of the head and neck, prostate 
cancer, gastric cancer, and testicular cancer, among others (DeVita 2001). This, in conjunction 
with paclitaxel’s cytotoxic mechanism of action, provides the basis for the investigation of 
nanoparticulate paclitaxel (formulated as SOR007) for the topical treatment of cutaneous 
metastases. Based on nonclinical studies of SOR007, it is believed that the nanoparticles will 
achieve a depot effect, providing a continuous dose of paclitaxel to the diseased skin over time 


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with limited systemic exposure. It is also anticipated that topical treatment of cutaneous metastases 
with SOR007 will be well tolerated, allowing for repeat administration if necessary. 
1.3 
Potential Risks and Benefits  
1.3.1 
Known Potential Risks  
There are currently no known risks associated with SOR007 applied topically to cutaneous 
metastases. 
Intravenous administration of paclitaxel can lead to AE. Systemic exposure to paclitaxel by 
injection, ingestion or inhalation was associated with following AE: 
• Bone marrow suppression; 
• Hypersensitivity reaction; 
• Hypotension; 
• Peripheral neuropathy; 
• Myalgia/Arthralgia; 
• Infection; 
• Mucositis; 
• Nausea/Vomiting; 
• Diarrhea; 
• Neurotoxicity; 
• Alopecia; 
• Renal impairment; 
• Hepatic impairment; 
• Hypospermatogenesis; 
• Injection site reaction. 
Most AE associated with paclitaxel are temporary and will resolve in time. However, time to 
resolution of specific AE is unknown and can vary widely depending on concomitant medications, 
therapies, and medical condition. 
Nonclinical studies have shown that paclitaxel can cause fetal harm when administered during 
pregnancy. There are no adequate and well-controlled clinical studies in pregnant women. If 
paclitaxel is used during pregnancy, or if a patient becomes pregnant while receiving paclitaxel, 
the patient should be apprised of the potential hazard to the fetus.  
1.3.2 
Known Potential Benefits  
There are currently no known benefits for SOR007 applied topically to cutaneous metastases. 


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2 
OBJECTIVES AND PURPOSE 
The primary objective of this study is to evaluate the safety and tolerability of topical SOR007 
ointment applied to cutaneous metastatic lesions. The secondary objectives are to obtain 
preliminary information on the efficacy of topical SOR007 ointment applied to the cutaneous 
metastatic lesions, reduction in pain and to describe the pharmacokinetics of topical SOR007 
Ointment. 
3 
STUDY DESIGN AND ENDPOINTS 
3.1 
Description of the Study Design 
This is a Phase 1/2, open-label, dose-rising study evaluating the safety, tolerability, and 
preliminary efficacy of three concentrations of SOR007 (0.15%, 1.0%, and 2.0%) applied topically 
to non-melanoma cutaneous metastases.  
Subjects will be screened and eligibility confirmed up to 14 days prior to treatment with SOR007.  
Safety Reviews 
Regular safety reviews will be conducted by the Medical Monitor on an ongoing monthly basis 
throughout the dose escalation and dose expansion portions of the study. Safety data to be reviewed 
will include, but will not be limited to, medical history, physical examinations, disease status, vital 
signs, concomitant medications, adverse events, and laboratory results. The CTCAE (version 4.0) 
criteria will be used to classify the severity of adverse events and determine dose limiting toxicity. 
The study will include a dose escalation phase and a dose expansion phase.  
Dose Escalation Phase: 
During the dose escalation phase, the study will follow a standard 3+3 dose-ascending design, with 
the first cohort commencing treatment on Day 1 with 0.15% SOR007 (see Figure 1). Dose 
escalation of SOR007 will be determined by the Safety Monitoring Committee (SMC) per the 
charter, which will be in place prior to the first subject entering the study. The SMC will review 
all available data after the last subject in each cohort of three subjects completes 15 days of 
treatment to determine whether dose escalation may continue.  
If a single dose limiting toxicity (DLT) is identified in one of three subjects in the cohort, a 
further three subjects will be enrolled at the same dose level. If one or more DLT occur in the 
three additional subjects enrolled in the cohort, dose escalation will stop and the prior dose level 
will be regarded as the Maximum Tolerated Dose (MTD) and taken forward into the dose 
expansion phase. If no further DLT are identified, dose escalation will continue, until either a 
DLT is identified at a higher dose or the top dose of 2% is reached.  


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Dose Expansion Phase: 
In the dose expansion phase, additional subjects will be enrolled to reach a maximum of 16 subjects 
at the dose level determined to be the MTD (or the top dose, 2.0% SOR007) in the dose escalation 
phase. The option of 28 or 56 days of treatment will be per investigatior decision, dependent on 
subject disease progression, additional systemic chemotherapy or other metastatic treatment 
requirements. 
3.2 
Primary Endpoint 
Safety and tolerability, as demonstrated by adverse events, changes in laboratory assessments, 
physical examination findings, and vital signs. 
3.3 
Secondary Endpoints 
• For the purposes of the following secondary endpoints for efficacy, eligible lesion 
measurements and analysis of photographs will be conducted by the sponsor using ImageJ. 
Eligible lesion identification will be performed by the Investigator at the clinical site at 
screening and confirmed at baseline for eligibility determination only, by the RECIST 
(version 1.1) definition of measurable tumors (≥ 10mm in its longest diameter) (Eisenhauer 
2009).  
o Objective tumor response, defined as the difference in the sum of eligible tumor 
diameter(s) within the treatment area between baseline and Day 43 or 70 (i.e. 14 
days after the last dose in the dose escalation and expansion phases depending on 
dose regimen). Tumor surface area and response will be assessed at all visits. 
Change in surface area will be assessed using a calibrated grid measurement system 
(ImageJ freeware) provided by the NIH. Photographs will be uploaded to a secure 
Citrix ShareFile or site restricted-access file, by a designated site staff member 
within 2 days of each visit. The Sponsor will measure and analyze the lesions using 
ImageJ as they are received. 
o Objective Clinical Response is defined as subjects with Complete Clinical 
Response (CR) + Partial Response (PR), further defined as the percentage of 
patients who achieve complete clinical response or partial response 14 days after 
the last treatment with SOR007, measured as change in the sum of the longest 
diameter(s) of eligible target lesion(s) within the treatment area 14 days after last 
treatment. The response to treatment is then evaluated as a function of post-
treatment total diameter divided by pre-treatment total diameter.  
o Best overall response is defined as the best response recorded from the start of study 
treatment until the end of the study (i.e. 28 Treatment days at Visit 6/Day 43 or 56 
Treatment days at Visit 7, Day 70).  
o Complete clinical response (CR) is defined as absence of any detectable residual 
disease in eligible lesion(s) within the treatment area; partial response (PR) as at 
least a 30% decrease in the sum of the diameters of the eligible lesion(s) within the 


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treatment area compared to baseline (Visit 2); and progressive disease (PD) as at 
least a 20% increase in the sum of diameters of eligible lesion(s) within the 
treatment area, taking as reference the smallest sum on study. In addition, the sum 
must also demonstrate an absolute increase of at least 5 mm. Stable disease (SD) is 
defined as the sum of eligible lesion diameter(s) between that defined as PR or PD. 
o The appearance of new non-target lesions during participation in this study does 
NOT constitute progressive disease. 
• Pain at the treatment area will be measured by the Numeric Rating Scale (NRS-11). Change 
in pain will be analyzed from baseline to Day 43 or 70. 
• To describe the pharmacokinetics of topical SOR007 Ointment applied to metastatic 
lesions. 
3.4 
Exploratory Endpoints 
Appearance of new lesions within the treatment area. 
4 
STUDY ENROLLMENT AND WITHDRAWAL 
4.1 
Participant Inclusion Criteria 
1. Signed informed consent; 
2. Male and female patients ≥ 18 years of age; 
3. Malignancies resulting in cutaneous metastasis originating from: breast, lung, head and 
neck, pancreatic, urinary bladder, prostate, testicular, ovarian, uterine, cervical, gastric, 
adrenal, thyroid, parathyroid cancers, or other solid tumors; 
4. Cutaneous metastases diagnosis confirmed prior to consent by preferred institutional 
methodology which may include, but is not limited to: biopsy; conventional radiography; 
imaging techniques to include bone scan (scintigraphy), computed tomography (CT), 
fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT), magnetic resonance 
imaging (MRI), F-fluoromisonidazole-(F-FMISO) PET/CT, fluorothymidine-(FLT) 
PET/CT, fluoroestradiol-(FES) PET/CT, and PET/MRI; 
5. ECOG Grade 0 – 2, with minimum life expectancy of at least 3 months;  
6. At least one baseline eligible lesion. Per RECIST criteria (version 1.1), an eligible lesion 
at baseline is considered measurable when ≥ 10mm diameter in the longest diameter; 
7. Willing to refrain from using lotions, creams, etc. during the treatment period to the 
treatment area;  
8. Subjects with adequate organ and bone marrow function as defined below: 
o ANC ≥ 1,500/µl 
o Hemoglobin ≥ 9.5 grams/dL 
o Platelets ≥ 75,000/µl 
o  AST (aspartate transaminase or SGOT)/ALT (alanine aminotransferase or SGPT) 
≤ 3.0 x ULN and total bilirubin ≤ 2.0 x ULN with no evidence of cholestasis  


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o Creatinine ≤ 1.5x ULN; 
9. Last dose of any systemic non-taxane cytotoxic chemotherapy completed at least one day 
prior to Day 1. Last dose of any systemic taxane cytotoxic chemotherapy completed at least  
4 weeks prior to Day 1; 
10. Willing to use appropriate birth control for patients of child-bearing potential; 
11. Abstinence from all manner of physical contact near the treatment area during and up to 2 
weeks after the treatment phase. 
4.2 
Participant Exclusion Criteria 
1. Open or ulcerated wound(s) extending through the dermis within the treatment area; 
2. Colorectal, hepatocellular, gallbladder, cholangiocarcinoma, neuroendocrine, melanomas, 
hematological and central nervous system (CNS) malignancies; 
3. Active viral hepatitis A, B, or C or preexisting or acute liver disease;  
4. Systemic treatment or localized treatment to target area with the following within the 4 
weeks prior to the first treatment visit: radiotherapy, intralesional therapy; laser therapy 
surgery (other than biopsy) local hyperthermia, levulinic acid, 5-fluorouracil, high potency 
corticosteroids (including systemic steroids), retinoids, diclofenac, hyaluronic acid, 
imiquimod; 
5. Elective surgery for treatment of the cutaneous metastases during the study and up to 4 
weeks after the treatment period. Cutaneous metastases are required to remain in-situ and 
measurable for up to 2 weeks after last treatment to achieve study objectives; 
6. Known allergic reactions, irritations or sensitivity to the active ingredients or other 
components of SOR007; 
7. Symptoms of a clinically significant illness that may place the subject at risk by trial 
participation or influence the outcome of the trial in the four weeks before first treatment 
and during the trial; 
8. Participation in the treatment phase of another clinical trial within the four weeks prior to 
treatment in this clinical trial; 
9. Investigator’s opinion of subject’s probable noncompliance or inability to understand the 
trial and/or give adequate informed consent; 
10. Evidence of current chronic alcohol or drug abuse; 
11. Pregnancy and/or lactating. 
4.3 
Strategies for Recruitment and Retention 
Sufficient subjects will be screened to allow for a minimum of three subjects up to a maximum of 
28 subjects to be enrolled in the trial. It is not anticipated that any advertising will be required for 
recruiting to the study. Subjects will be recruited and screened for eligibility and will proceed to 
treatment in cohorts of three. A low ECOG grade is required to maximize the probability that 
subjects will participate for the full duration of the study. 
Total study duration is estimated at about 15 months. 


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4.4 
Participant Withdrawal or termination 
4.4.1 
Reasons for Withdrawal or Termination 
Subjects are free to withdraw from participation in the study at any time upon request. Any reason 
for withdrawal and/or early termination will be documented in the source notes and in the 
Electronic Data Capture system (EDC).  
Other than the potential for local toxicity reactions, there is no reason currently anticipated that 
would cause the Investigator to terminate a subject’s participation in the study once treatment has 
been initiated. It is very important that any events occurring be captured and followed for the safety 
of the subject.  
Subjects may be non-compliant with the study protocol in a way that much of the data is not 
captured which would usually require withdrawal for non-compliance. For the purposes of this 
study, subjects should not be withdrawn in this situation.  
Clinical AE, laboratory abnormalities, or other medical conditions/situations may occur which 
would usually require cessation of study treatment. In these instances, it is very important that all 
of these events be captured, followed, and documented, and therefore a subject should not be 
withdrawn but rather followed up to study completion. 
Should the Investigator feel it to be in the best interest of the subject to be withdrawn from the 
study, the Investigator will immediately contact the Medical Monitor to discuss the reasons for 
withdrawal. 
4.4.2 
Handling of Participant Withdrawals or Termination 
The sponsor should be notified immediately when a subject is removed or withdrawn from the 
study after treatment with investigational agent. Every attempt should be made to capture as much 
information following treatment as possible.   
In the event a subject is withdrawn they would undergo final study visit evaluations (Visit 6 End-
of-Study evaluations) which include but are not limited to vital signs, AE collection and 
concomitant medication updates.   
Subjects that refuse or fail to appear for clinic visits following SOR007 treatment and fail to 
respond to or cooperate with reasonable and diligent attempts at contact should not be discontinued 
from the study but be considered lost-to-follow-up. Reasonable and diligent contact attempts 
should be documented appropriately to include dates and phone call details. Emails and registered 
mail correspondence should be filed in the subject’s medical record to document due diligence. 
If a subject repeatedly misses study visits or remains non-compliant following SOR007 treatment, 
and where the majority of data is not available, the option to replace that subject in the cohort 
exists, however the data that is collected from the non-compliant subject may still be used in the 
evaluations in this study. 


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4.5 
Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated by the site or sponsor for 
sufficient reasonable cause. Written notification, documenting the reason for the study suspension 
or termination, will be provided by the suspending or terminating party to sponsor. If the study is 
prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the 
reasons for the termination or suspension. 
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants; 
• Insufficient compliance with protocol requirements; 
• Data that are not sufficiently complete and/or evaluable; 
• Determination of futility 
o During the dose escalation phase, the majority of the lesions in the 50 cm2 
treatment area of study subjects who receive the maximum tolerated dose of 
SOR007 are found to increase in size at the end of the 28 or 56 days of treatment 
period. If the study is considered futile, it will be terminated and the dose 
expansion phase will not proceed. 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed 
and satisfy the sponsor, IRB, and/or FDA. 
5 
STUDY DRUG 
5.1 
Study Drug(s) Description 
5.1.1 
Acquisition 
The drug substance, paclitaxel, USP, is supplied by Phyton Biotech, LLC, Delta, BC, Canada. 
Bulk paclitaxel is converted to nanoparticles using a PCA technique, which employs supercritical 
carbon dioxide and acetone to generate paclitaxel nanoparticles within a well- characterized 
particle size distribution. The study drug, SOR007, will be manufactured by Dow Development 
Laboratories (DDL) and provided for use in this study as an ointment.  
The study drug will not be shipped to the study site until all Regulatory Documentation has been 
provided by the site and the site is ready for study Initiation, at which time the study drug will be 
released for shipment. Shipment will be via courier, temperature controlled 68˚ to 77˚F (20˚ to 
25˚C) and will occur prior to and in conjunction with the Site Initiation visit. Study drug will be 
shipped to the site Pharmacy where it will be stored according to the conditions required (see 
5.1.3). 


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5.1.2 
Formulation, Appearance, Packaging, and Labeling 
The study drug, SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment, is formulated with 
nanoparticulate paclitaxel at levels ranging from 0.15% to 2% suspended in an a sealed 15g 
laminate tube and will be labeled to include the following: 
Subject #: __________________ 
Date Opened ______ / ______ / ______ 
Study Number: SOR007 - __________________________________ 
Product Name: SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment X%, 15 g   
Store at 20-25°C (68-77°F)  
Keep out of the reach of children.  
Caution: New Drug – Limited by Federal (or United States) Law to investigational use. 
DFB Soria, LLC, US Biotest, 231 Bonetti Drive, Suite 240, San Luis Obispo, CA 93401 
5.1.3 
Product Storage and Stability 
Stability studies show that SOR007 ointment is stable when stored at controlled room temperature 
(25 °C/60% relative humidity) for up to 6 months and accelerated conditions (40 °C/75% relative 
humidity) for up to 6 months. 
Prior to administration at the hospital/clinic, the SOR007 ointment tubes will be stored at the 
Pharmacy, temperature controlled at 20˚ to 25˚C (68˚ to 77˚F); excursions permitted between 15-
30°C (59-86°F). 
5.1.4 
Preparation 
SOR007 will be supplied as finished drug product in small tubes. 
5.1.5 
Dosing and Administration 
Application of SOR007 will occur twice daily, at approximately the same times each day (morning 
and evening), for 28 or 56 days. Using a gloved hand, subjects will self-apply one Finger Tip Unit 
(FTU) of SOR007 to the entire 50 cm2 treatment area previously outlined by the delegated study 
staff in permanent marker. Note: There may be multiple lesions in the 50 cm2 marker-outlined 
area. 
A FTU is defined as the amount of ointment expressed from a tube with a 5 mm diameter nozzle, 
applied from the distal skin-crease to the tip of the index finger of an adult. The "distal skin-crease" 
is the skin crease over the joint nearest the end of the finger. One FTU will cover approximately 
50cm2, the entire treatment area.  One FTU = 0.5 g, which will amount to approximately 1 g/day 
or 7 g/week of ointment.  
Prior to administration of SOR007, the treatment area should be gently cleansed. Apart from drug 
application and area cleansing, all physical touching of the treatment area, including application 
of oils, creams and harsh soaps, is to be strictly avoided. Subjects will be provided with an 
instruction card as a guide for application and will receive application training by study staff at 
Visits 2, 3, 4 and 5, as needed. 


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5.1.6 
Route of Administration 
Topical. 
5.1.7 
Dosing and Dose Escalation  
This study will be conducted in two phases: a dose escalation phase structured with a standard 3+3 
dose-ascending design (Figure 1) and a dose expansion phase enrolling sufficient subjects to reach 
a maximum of 16 total subjects total at the maximum tolerated dose (MTD) or highest dose of 
SOR007 (0.15%, 1.0% or 2.0%) as determined in the dose escalation phase (see Section 7.6).  
Safety reviews for decisions on dose escalation will be conducted after the last subject in each 
cohort of three subjects completes 15 days of treatment. Guidance on the criteria to be used in the 
determination of the benefit/risk balance for dose escalation can be found in Section 7.5 Study 
Halting Rules. 
5.1.8 
Dose Adjustments/Modifications/Delays 
None.   
5.1.9 
Duration of Treatment 
Twice-daily dosing will begin on Day 1 and continue up to Day 28 or 56 if no DLT are observed. 
If all lesions within the treatment area resolve at any point during treatment, the Investigator may 
determine that it is in the best interest of the subject to cease treatment with SOR007.  
28 Treatment Days 
If treatment with SOR007 ceases at any point prior to Day 28 treatment subjects should complete 
Visit 6 - End of Study procedures and the Visit 7 safety assessment study evaluations (See 6.5.4).  
56 Treatment Days 
If treatment with SOR007 ceases at any point prior to Day 56 treatment subjects should complete 
Visit 7 - End of Study procedures and the Visit 8 safety assessment study evaluations (See 6.5.4).  
Due to the nature of both the disease and of paclitaxel, it is possible that the epithelial/dermal 
covering over the treated target cutaneous metastatic lesion will break down after initiation of 
treatment with SOR007. SOR007 may, in this scenario, continue to be applied to the treatment 
area. If new ulceration occurs, this is considered a DLT. Following review of the study data, the 
Medical Monitor will provide written documentation confirming all treatment cessations for each 
applicable subject.   
5.1.10 
Dosing Compliance 
Subject compliance will be tracked by visual inspection of the returned SOR007 ointment tubes 
and weighing of the returned SOR007 ointment tubes. At the baseline visit, the sealed, unused 
SOR007 ointment tube will be weighed in the site pharmacy when given to the subject to obtain 


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the full tube baseline weight. Each dispensed SOR007 ointment tube will be weighed again by 
the pharmacy when returned by the subject. This step (weighing of tubes) may also be conducted 
by the clinic personnel per institution policy. Scales and calibration weights may be provided to 
sites where there is no access to a ‘weighing scale’. The subjects will be trained to self-dose 
(application) by delegated study staff. The subjects will apply the first dose to the ‘marker-
outlined area’ under study staff supervision. Subjects will be instructed on how to care for the 
treatment area (cleansing), what to avoid (creams, lotions, harsh soaps), SOR007 storage and 
requirements to bring SOR007 ointment tubes to each subsequent visit (Visits 3, 4, 5 or 6, if 
applicable), at which point all returned tubes will be visually inspected and weighed in the 
pharmacy. The subjects will be provided new SOR007 ointment tube(s) at Visits 2, 3, 4 or  5, if 
applicable. Subjects may use any SOR007 ointment tube(s) until it is empty, before starting a 
new SOR007 ointment tube. Subjects will also be provided an instruction card at the study start 
and a diary at each clinic visit as a dosing reminder and to document all SOR007 self-dosing 
details, adverse events and concomitant medications taken. For subjects that have difficulty 
applying the study drug or requiring assistance, a care-giver or spouse may be trained in study 
drug application, if allowed by the institution and/or IRB. 
5.2 
Study Drug Accountability Procedures 
The Investigator or designee will maintain adequate records showing the receipt, dispensing, 
return, or other disposition of the study drug, including the date, quantity, batch or code number 
(if applicable), and identification of subjects (number, initials (as allowed by local confidentiality 
requirements)) who received study medication. 
Accountability will be conducted on the individual tubes. 
Used tubes will be retained in the Pharmacy for accountability purposes and will not be disposed 
of until sponsor accountability monitoring is completed. Used tubes will be retained in the clinic 
until the site receives sponsor directives for used/unused study drug tube return to the sponsor or 
delegate. 
Under no circumstances will the Investigator supply clinical material to other Investigators or 
clinicians or allow the supplies to be used other than as directed by this protocol without prior 
written permission from the sponsor. 
6 
STUDY PROCEDURES AND SCHEDULE 
6.1 
Study Procedures/Evaluations 
6.1.1 
Study Specific Procedures  
The following procedures and evaluations will be performed as part of this study: 
• Review and documentation of demographics, significant past and current medical history, 
including allergies; 


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• Review and documentation of concomitant prescription and non-prescription medications; 
• Review and documentation of diagnosis of cutaneous metastases of non-melanoma origin 
and previous treatments including surgical and chemotherapeutic records;  
• A pregnancy test at screening for female subjects; 
• A comprehensive physical examination at screening only; at all subsequent visits, the 
investigator will perform a physical examination only if deemed necessary, otherwise no 
physical examination needed per protocol; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature); 
• Body weight and height (at screening only); 
• Pain at the treatment area will be assessed with the Numeric Rating Scale (NRS-11) at 
screening Visit 1 and at each study visit. 
• Measurement of lesions with calipers;  
• Photography of the treatment area (Section 6.3)  
• SOR007 to be applied topically to the treatment area by gloved hand twice daily for 28 or 
56 days; 
• Blood samples for routine hematology and serum chemistry at every visit;  
• PK blood collection at 24 hours after the first application (Day 1/Visit 2 plus 24 hours), 
and Visits 3, 4, 5 and 6 and 7, if applicable.  
• Urine dipstick at screening and last subject visit; and  
• Subject diary to be completed daily. 
• Every effort should be made to schedule the subject clinic visits early in the morning to 
ensure the ‘morning’ and ‘evening’ application routines are adhered to and conducted at 
approximately the same time every day.   
6.1.2 
Standard of Care Study Procedures  
Standard of care treatment at the Investigator’s institution is not part of this study. Medical care 
during this study is at the discretion of the Investigator. At the time of the first study drug dose, 
the subject should not be scheduled for systemic chemotherapy. If, after the first study drug dose 
application, due to progression of disease or at the Investigator’s discretion, the need arises for 
chemotherapeutic intervention, such treatment will be initiated at any time during the conduct of 
the study (See 6.6). All treatments and medications must be recorded in the subject’s record. 
Surgical excision may only be scheduled at least 4 weeks after last treatment with SOR007 in order 
to achieve the objectives of this study. If the Investigator determines that it is in the subject’s best 
interest to receive surgical excision or other prohibited treatment sooner than four weeks after last 


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treatment with SOR007, the subject will be permitted to receive such treatment in accordance with 
Section 6.6.2. 
6.2 
Treatment Area Selection 
At baseline (Visit 2), the Investigator will identify a treatment area of 50 cm2 containing at least 
one eligible lesion. Per RECIST criteria (version 1.1), an eligible lesion is considered measurable 
when ≥ 10mm diameter in the longest diameter. 
The Investigator will outline the treatment area in permanent marker. All lesions within the 
treatment area will be measured by caliper at baseline to confirm eligibility and will be documented 
in the source. There may be multiple lesions present, in addition to the target lesion, in the 50 cm2 
outlined area. All lesions in the treatment area will be measured and tracked as described in this 
protocol (Section 3.3). 
6.3 
Photographic Documentation 
The sponsor will provide detailed procedures for Photographs in the Procedure Manual.  
Photographic documentation using a standard focal length digital camera of the treatment areas 
will be performed at baseline (Day 1/Visit 2) and at each subsequent study visit (Days 8, 15, 29, 
and  57, and 70, if applicable) or early withdrawal from the study, as applicable. The photographs 
will be taken under standardized conditions. Cameras and associated equipment will be provided 
to all Investigators, if needed. At least two global photos will be taken to reference the treatment 
area’s location on the subject’s body and at least two close-up photos of the treatment area will be 
taken. In every close-up photo, the required photographic documentation of the treatment area will 
include a centimeter ruler to reference scale and a label with the subject number, calendar date and 
study visit number. No non-study specific information will be included in the label. Study staff 
will be instructed to upload the subject photographs to a secure, password protected Citrix 
ShareFile or site restricted-access file, that will be accessible only by the site, the Medical Monitor, 
and the Sponsor. The Sponsor will analyze the images and measure the lesions using the Image J 
JAVA image processing program as photographs are uploaded by the Investigator. 
6.4 
Laboratory Procedures/Evaluations 
6.4.1 
Clinical Laboratory Evaluations  
Clinical laboratory assessments will be conducted at the local CLIA certified laboratory routinely 
used by the Investigator. 
The following laboratory tests will be performed at the Screening visit and Visits 2-6, and 7, if 
applicable: 
• Routine complete total blood count including red blood cells (RBC), white blood cells 
(WBC), hemoglobin, hematocrit, platelets, mean corpuscular hemoglobin (MCH), mean 
corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and 


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complete differential to include absolute and relative counts for all hematological 
parameters measured; 
• 
Serum Chemistry, including albumin, total bilirubin, liver function tests (AST, ALT, GGT, 
ALP), blood urea nitrogen (BUN), creatinine, sodium, potassium, calcium, chloride, 
magnesium, and total protein;  
• 
Urinalysis (dipstick), including specific gravity, pH, RBC, WBC, protein, and glucose will 
be performed at screening and Visit 7 for each subject.  
6.4.2 
Other Assays or Procedures  
Blood samples will be collected to analyze pharmacokinetic (PK) activity for all subjects. Samples 
will be collected at 24 hours after the first application (Day 1/Visit 2 plus 24 hours), Visits 3, 4 
and 5 (prior to the first daily application); Visits 6 and 7 (at any time during the visit).  
6.5 
Study Schedule 
6.5.1 
Screening 
Visit 1 (Days -13 to Day 0)  
The following screening procedures and assessments must be completed, documented and 
reviewed by the Investigator, within 14 days prior to the first topical SOR007 ointment 
administration. Institution standard of care laboratory and clinical assessments will be allowed if 
obtained prior to consent only if performed within the screening timeperiod or 14 days prior to 
Day 1: 
• Written informed consent including comprehensive discussion of the study schedule, 
procedures and subject protocol requirements; 
• Review of previous medical records, demographics, allergies, significant past medical 
history; 
• Review and documentation of concomitant prescription and non-prescription medications; 
• Review and documentation of diagnosis of cutaneous metastases of non-melanoma origin 
and previous treatments including surgical and chemotherapeutic records;  
• A comprehensive physical examination;  
• Vital signs (blood pressure, heart rate, respiration rate), temperature, body weight and 
height;  
• ECOG performance status; 
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11); 


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• Lesions will be measured with calipers. The target lesion will be determined at baseline by 
the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest 
diameter); 
• Blood samples for routine hematology and serum chemistry, as per Section 6.4.1;  
• Urinalysis by dipstick; 
• Pregnancy test for female subjects; 
• Review of inclusion and exclusion criteria and determination of eligibility. 
6.5.2 
Enrollment/Baseline 
Visit 2 (Day 1) 
The following procedures and assessments must be completed, documented and reviewed by the 
Investigator prior to the intended topical SOR007 ointment application: 
• Medical history updates to include any events occurring since Visit 1, up to the first study 
treatment application; 
• Review and documentation of current concomitant prescription and non-prescription 
medications; 
• A problem-oriented physical examination, only if determined necessary by Investigator; 
• Vital signs measurement (blood pressure, heart rate, respiration rate, temperature); 
• Lesions will be measured with calipers. The target lesion will be confirmed at baseline by 
the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest 
diameter). All other lesion(s) in the treatment area will also be measured.  
• Routine hematology, serum chemistry and urinalysis. 
• Review of inclusion and exclusion criteria and determination of eligibility up to just prior 
to the first study treatment application, to confirm proceeding to treatment. After these 
assessments have been completed, the subject will receive topical application of SOR007.  
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11) to be 
assessed prior to treatment area cleansing or drug application; 
• The 50 cm2 treatment area containing at least one eligible lesion will be selected by the 
Investigator, washed with warm soapy water and outlined with a permanent marker; 
• Each lesion within the treatment area will be documented in the source and tracked for the 
duration of the study for changes in size and appearance; 
• Photography of the treatment area and eligible lesion(s), incorporating a ruler for size 
evaluation; 


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• 
For this first application, the Investigator will demonstrate proper application technique as 
described in Section 5.1.5.  
The subject will be supplied with the appropriate number of tubes of SOR007 for treatment 
application (until Visit 3) and a subject diary for daily completion. The subject will be instructed 
to self-apply SOR007 twice daily and to bring with them the SOR007 ointment tube to Visit 3 
(Day 8). 
 
PK Collection 24 Hours (+/- 2 hrs) 
The subject will return to the clinic for PK sample collection at 24 hours (+/- 2 hours) after the 
Visit 2/Day 1 first SOR007 ointment application. 
6.5.3 
Treatment  
Visit 3 (Day 8 ± 1 Day) 
• Subject will return used SOR007 ointment tube for dosing compliance (Section 5.1.10) 
and study drug accountability (Section 5.2) purposes; 
• Review and documentation of concomitant prescription and non-prescription 
medications; 
• A problem-oriented physical examination only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate and temperature);  
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11) prior to 
treatment area cleansing or drug application; 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
evaluation; 
• Blood sample collection for routine hematology and serum chemistry, as per Section 6.4.1; 
• Day 8 PK sample collection prior to study drug application; 
• Application of SOR007; 
• Adverse events review; 
• Subject will be supplied with the appropriate number of tubes of SOR007 for treatment 
application until the next visit; 
• Subject diary from Visit 2 will be reviewed to confirm it is adequately completed. The 
subject will be questioned regarding discrepancies, missing entries and errors. Any 
discrepancy will be documented in the subject source documents by a delegated staff; and 
• A new diary to be provided to the subject for daily completion. 


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Visit 4 (Day 15 ± 1 Day) 
• Subject will return SOR007 ointment tube for dosing compliance (Section 5.1.10) and 
study drug accountability (Section 5.2) purposes; 
• Review and documentation of concomitant prescription and non-prescription medications; 
• A problem-oriented physical examination only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature);  
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11) prior to 
treatment area cleansing or drug application; 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
evaluation; 
• Blood sample collection for routine hematology and serum chemistry, as per Section 6.4.1; 
• Day 15 PK sample collection prior to study drug application; 
• Application of SOR007; 
• Adverse events review; 
• Subject will be supplied with the appropriate number of tubes of SOR007 for treatment 
until the next visit; 
• Subject diary from Visit 3 will be reviewed to confirm it is adequately completed. The 
subject will be questioned regarding discrepancies, missing entries and errors. Any 
discrepancy will be documented in the subject source documents by a delegated staff; and 
• A new Visit 4 diary to be provided to the subject for daily completion. 
Visit 5 (Day 29 + 2 Days) 
• Subject will self-apply the last dose of SOR007 the evening prior to the visit; 
• Day 29 PK sample collection at any time during the visit;  
• Blood samples will be collected for routine hematology and serum chemistry, as per 
Section 6.4.1; 
• Review and documentation of concomitant prescription and non-prescription medications; 
• A problem-oriented physical examination; only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature);  
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11); 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
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• Subject will return SOR007 ointment tube for dosing compliance (Section 5.1.10) and 
study drug accountability (Section 5.2) purposes; 
• Adverse events review;  
• Subject diary from Visit 4 will be reviewed to confirm it is adequately completed. The 
subject will be questioned regarding discrepancies, missing entries and errors. Any 
discrepancy will be documented in the subject source documents by a delegated staff. 
• A new Visit 5 diary to be provided to the subject for daily completion. 
This visit will constitute the End-of-Treatment visit for Group A subjects. All subjects will be 
required to complete a 30-day safety follow-up period (including Visits 6 and 7 for Group A and 
Visits 7 and 8 for Group B in the dose expansion phase). 
Subjects in the dose expansion phase continuing to an additional 28 days of treatment (or 56 
treatment days) will proceed to Treatment B Visit 5 procedures: 
• Application of SOR007; 
• Adverse events review; 
• Subject will be supplied with the appropriate number of tubes of SOR007 for treatment 
until the next visit.  
Group B Visit 6 (Day 57 + 2 Days) 
• Subject will self-apply the last dose of SOR007 the evening prior to the visit; 
• Day 57 PK sample collection;  
• Blood samples will be collected for routine hematology and serum chemistry, as per 
Section 6.4.1; 
• Review and documentation of concomitant prescription and non-prescription medications; 
• A problem-oriented physical examination; only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature);  
• Pain assessment of the treatment area with the Numeric Rating Scale (NRS-11); 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
evaluation; 
• Subject will return SOR007 ointment tube for dosing compliance (Section 5.1.10) and 
study drug accountability (Section 5.2) purposes; 
• Adverse events review;  


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• Subject diary from Visit 5 will be reviewed to confirm it is adequately completed. The 
subject will be questioned regarding discrepancies, missing entries and errors. Any 
discrepancy will be documented in the subject source documents by a delegated staff. 
• A new Visit 6 diary to be provided to the subject for daily completion. 
This visit will constitute the End-of-Treatment visit for Group B subjects. All subjects will be 
required to complete a 30-day safety follow-up period (including Visits 7 and 8). 
6.5.4 
Follow up and End-of-Study Evaluations: Group A  
Visit 6 (Day 43 ± 2 Days) End-of-Study Evaluations 
• Day 43 PK sample collection at any time during the visit;  
• Review and documentation of concomitant prescription and non-prescription medications; 
• Problem-oriented physical examination only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature);  
• Pain assessment of the treatment area; 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
evaluation; 
• Blood samples will be taken for routine hematology and serum chemistry; 
• Urinalysis by dipstick;  
• Adverse events review; 
• Subject diary from Visit 5 will be collected and reviewed to confirm it is adequately 
completed. The subject will be questioned regarding discrepancies, missing entries and 
errors. Any discrepancy will be documented in the subject source documents by a delegated 
staff.   
Visit 7 (Day 59 + 2 Days) - Final Visit 
Thirty days following the last study drug application all subjects must complete a final visit. The 
visit may be conducted at the Investigator’s discretion as a clinic/office visit or by phone. During 
this visit the site will follow up on any existing adverse events and record any new adverse 
events. If the visit is conducted in the clinic/office, a physical exam may be conducted, only if 
deemed necessary by the Investigator. If the visit is conducted by phone, all phone call details 
must be recorded in the subject source. 
6.5.5 
Follow up and End-of-Study Evaluations: Group B  
Visit 7 (Day 70 ± 2 Days) End-of-Study Evaluations 
• Day 70 PK sample collection;  


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• Review and documentation of concomitant prescription and non-prescription medications; 
• Problem-oriented physical examination only if determined necessary by Investigator; 
• Vital signs (blood pressure, heart rate, respiration rate, temperature);  
• Pain assessment of the treatment area; 
• Photography of the treatment area and eligible lesions, incorporating a ruler for size 
evaluation; 
• Blood samples will be taken for routine hematology and serum chemistry; 
• Urinalysis by dipstick;  
• Adverse events review; 
• Subject diary from Visit 6 will be collected and reviewed to confirm it is adequately 
completed. The subject will be questioned regarding discrepancies, missing entries and 
errors. Any discrepancy will be documented in the subject source documents by a delegated 
staff.   
Visit 8 (Day 86 + 2 Days) - Final Visit 
Thirty days following the last study drug application all subjects must complete a final visit. The 
visit may be conducted at the Investigator’s discretion as a clinic/office visit or by phone. During 
this visit the site will follow up on any existing adverse events and record any new adverse 
events. If the visit is conducted in the clinic/office, a physical exam may be conducted, only if 
deemed necessary by the Investigator. If the visit is conducted by phone, all phone call details 
must be recorded in the subject source. 
6.5.6 
Early Termination Visit 
In the event a subject, from either group is withdrawn they would, at minimum, undergo the End-
of-Study (Visit 6 or 7) evaluations. If a subject is withdrawn at a routine study visit, all evaluations 
that would have been done at that study visit should be completed as well as all End-of-Study 
evaluations. If a subject received any study drug application, an additional safety assessment must 
be completed thirty days (+ 2 days) following the last study drug application (see 6.5.4/Visit 7 or 
6.5.5/Visit 8). 
6.5.7 
UNSCHEDULED VISIT 
Any unscheduled visits will be documented in the subject source notes/clinic or hospital chart and 
any assessments and/or evaluations performed will be noted and reviewed. The subject will 
undergo any other evaluations determined necessary by the Investigator to ensure the subject’s 
well-being. If the Investigator deems it necessary to perform additional evaluations outside the 
scope of this study, this information will be documented in the subject source documents and 
collected for study purposes. 


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6.5.8 
Schedule of Events Table 1: Treatment Group A: 28 Days 
Timepoint/Study Visit 
Screening  
( < 14 days) 
Baseline 
Treatment 
Follow up 
Visit 1 
(Days -13 to Day 0) 
Day 1 / 
Visit 2 
Day 8 / Visit 3 
(+/- 1 d) 
Day 15 / Visit 4 
(+/- 1 d) 
Day 29 / Visit 5 
(+ 2 d) 
Day 43 / Visit 6 
(+/- 2 d) 
Day 59 / 
Visit 7 (+ 2 d) 
Informed Consent 
X 
 
 
 
 
 
 
History and Demographics1 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X2 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
 
Vital Signs4 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
Hematology and Chemistry 
X 
 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
 
Pharmacokinetic (PK) Assay5 
 
X 
X 
X 
X 
X 
 
Pain Assessment  
X 
X 
X 
X 
X 
X 
 
Tumor Measurements6 
X 
X 
 
 
 
 
 
Tumor Assessment7 
 
 
X 
X 
X 
X 
 
Photography 
 
X 
X 
X 
X 
X 
 
Distribute SOR007 Tube(s) 
 
X 
X 
X 
 
 
 
Collect SOR007 Tube(s) 
 
 
X 
X 
X 
 
 
SOR007 Application Training7 
 
X 
X 
X 
 
 
 
SOR007 Application7 
 
X 
X 
X 
 
 
 
Adverse Events8 
X 
X 
X 
X 
X 
X 
X10 


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Concomitant Therapy 
X 
X 
X  
X 
X  
X 
 
Diary Distribution9 
 
X 
X 
X 
X 
 
 
Diary Collection 
 
 
X 
X 
X 
X 
 
1  
History includes all medical and surgical events prior to SOR007 treatment application. 
2  
Final determination of study eligibility to be confirmed prior to first study drug application. 
3  
A comprehensive physical examination to be completed at the screening visit only; problem-oriented physical exam to be completed at all other visits, 
as needed. 
4  
Vital signs include: blood pressure, heart rate, respiration rate and temperature. 
5.  
PK samples will be collected 24 hours (+/- 2 hours) post the first study drug application; at Visits 3 and 4 (prior to the first daily application); at Visit 5 
and Visit 6 (at any time during the visit).  
6  
Cutaneous metastatic lesions will be measured with calipers at Screening to determine eligibility and at Baseline to document the ‘starting dimensions’ 
if different from screening. Eligible lesions will be determined by the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest 
diameter).  
7 
Lesions identified at Baseline, will be observed, tracked and documented for changes on a Lesion tracking log by the investigator at each visit. 
8 SOR007 will be administered by topical application to metastatic lesions by the Subject following training by the Investigator or delegated study staff. 
Assigned SOR007 cohort dose will be applied daily on Day 1 to Day 28.  
9 
All adverse events and treatment emergent adverse event (TEAE) determination will start immediately following initiation of study treatment. 
10  
Subject Diary to be completed daily as an ointment dose application self-reminder and to record all ointment dose applications, record AEs and CMs. 
11 
The final safety assessment to be performed 30 days (+ 2 days) after last study drug dose application. The decision to conduct the visit in clinic or by 
phone is at the investigator discretion. 
 


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6.5.9 
Schedule of Events Table 2: Treatment Group B: 56 Days 
Timepoint/Study Visit 
Screening  
( < 14 days) 
Baseline 
Treatment 
Follow up 
Visit 1 
(Days -13 - 0) 
Day 1 / 
Visit 2 
Day 8 /  Visit 3 
(+/- 1 d) 
Day 15 / Visit 4 
(+/- 1 d) 
Day 29 / Visit 5 
(+/- 2 d) 
Day 57 / Visit 6 
(+/- 2 d) 
Day 70 / Visit 7 
(+/- 2 d) 
Day 86 / Visit 8  
(+ 2 d) 
Informed Consent 
X 
 
 
 
 
 
 
 
History and Demographics1 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X2 
 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signs4 
X 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
 
Hematology and Chemistry 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
Pharmacokinetic (PK) 
Assay 
 
X5 
X 
X 
X 
X 
X 
 
Pain Assessment  
X 
X 
X 
X 
X 
X 
X 
 
Tumor Measurements6 
X 
X 
 
 
 
 
 
 
Tumor Assessment7 
 
 
X 
X 
X 
X 
X 
 
Photography 
 
X 
X 
X 
X 
X 
X 
 
Distribute SOR007 Tube(s) 
 
X 
X 
X 
X 
 
 
 
Collect SOR007 Tube(s) 
 
 
X 
X 
X 
X 
 
 
SOR007 Application 
Training8 
 
X 
X 
X 
X 
 
 
 
SOR007 Application8 
 
X 
X 
X 
X 
 
 
 
Adverse Events9 
X 
X 
X 
X 
X 
X 
X 
X11 


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Concomitant Therapy 
X 
X 
X  
X 
X  
X  
X 
 
Diary Distribution10 
 
X 
X 
X 
X 
X 
 
 
Diary Collection 
 
 
X 
X 
X 
X 
X 
 
 
1  
History includes all medical and surgical events prior to SOR007 treatment application. 
2  
Final determination of study eligibility to be confirmed prior to first study drug application. 
3  
A comprehensive physical examination to be completed at the screening visit; problem-oriented physical exam to be completed at all other visits as 
needed; 
4  
Vital signs include: blood pressure, heart rate, respiration rate and temperature. 
5.  
PK samples will be collected 24 hours (+/- 2 hours) post the first study drug application; at Visits 3, 4 and 5 (prior to the first daily application, at Visits 
6 and 7 at any time during the visit.  
6  
Cutaneous metastatic lesions will be measured with calipers at Screening to determine eligibility and at Baseline to document the ‘starting dimensions’ 
if different from screening. Eligible lesions will be determined by the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest 
diameter).  
7 
Lesions identified at Baseline, will be observed, tracked and documented for changes on a Lesion tracking log by the investigator at each visit. 
8  
SOR007 will be administered by topical application to metastatic lesions by the Subject following training by the Investigator or delegated study staff. 
Assigned SOR007 cohort dose will be applied daily on Day 1 to Day 56.  
9 
All adverse events and treatment emergent adverse event (TEAE) determination will start immediately following initiation of study treatment. 
10  
Subject Diary to be completed daily as an ointment dose application self-reminder and to record all ointment dose applications, record AEs and CMs. 
11 
The final safety assessment to be performed 30 days (+ 2 days) after last study drug dose application. The decision to conduct the visit in clinic or by 
phone is at the investigator discretion. 


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6.6 
Concomitant Medications, Treatments, and Procedures  
Any medication ongoing at the time of the first study drug application will be collected and 
recorded for study purposes. These will be considered baseline medications. Any new 
medication started after the first study drug application, or medication changed from baseline 
will be collected and recorded on the electronic case report forms (eCRF). Following Visit 2/Day 
1, if disease progression requires chemotherapy treatment, any treatment can be administered at 
the discretion of the Investigator. If a taxane treatment is indicated, the subject will be withdrawn 
from the study (See 6.1.2, 6.5.5).  
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications and/or treatments to be reported in the 
eCRF are concomitant prescription medications, over-the-counter medications, and non-
prescription medications. 
6.6.1 
Precautionary Medications, Treatments, and Procedures 
No precautionary medications, treatments, or procedures are included in this protocol; they may, 
however, be administered at the discretion of the Investigator or the subject’s primary care provider 
or oncologist unless a prohibited medication (See 6.6.2); all medications will be recorded.  
6.6.2 
Prohibited Medications, Treatments, and Procedures  
Systemic treatment or treatment to the target area with radiotherapy, intralesional therapy; laser 
therapy surgery other than biopsy, local hyperthermia, levulinic acid, 5-fluorouracil, high 
potency corticosteroids (including systemic steroids), retinoids, diclofenac, hyaluronic acid, 
imiquimod within the 4 weeks prior to the screening visit are prohibited. Subjects should not be 
scheduled to receive any systemic taxane cytotoxic chemotherapy, or topical or direct lesional 
therapy (e.g. intralesional injections, laser, hyperthermia, and steroids to within 2 inches (5 cm) 
of the 50 cm2 treatment area) within 2 weeks prior to the first study drug application or during 
the study. Following Visit 2/Day 1, if disease progression requires taxane chemotherapy 
treatment, the subject will be removed from the study (i.e.: study drug treatments to be 
discontinued). All early termination assessments (Visit 6 or 7) as well as the 30 days post last 
study drug dose application contact will be required to be completed. 
If the Investigator determines that any prohibited medications or procedures are required in the 
best interests of the subject, the subject will receive the treatment or procedure. When this 
occurs, discussion with the Medical Monitor is required, the subject is to discontinue further 
treatment with SOR007, and complete Visit 6 or 7 and 30 days post last study drug dose 
application call or visit, per protocol.  
6.6.3 
Prophylactic Medications, Treatments, and Procedures  
No specific prophylactic medications are required for this study. While prophylaxis is commonly 
administered to subjects receiving intravenous paclitaxel, clinically significant systemic exposure 


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is not expected with topical administration of SOR007 under the conditions of this study. Routine 
prophylaxes may be instituted if signs and symptoms suggest the need, provided these are not 
prohibited medications, treatments or procedures (see Section 6.6.2).  
 
7 
ASSESSMENT OF SAFETY 
7.1 
Specification of Safety Parameters 
Safety assessments being conducted in this study include: 
• Laboratory assessments; 
• Adverse events and TEAE, collected at all study visits from the time of initial dosing; 
• Changes in concomitant medications and; 
• Findings from physical examinations. 
Safety will be reviewed by the Medical Monitor in an ongoing manner via the EDC system, and 
details will be confirmed at routine on-site monitoring visits. 
7.1.1 
Definition of Adverse Events (AE) and Adverse Drug Reaction (ADR) 
An AE is any untoward medical occurrence (whether or not considered to have a causal 
relationship to the study drug) in a study subject administered the study drug. Therefore, an AE 
can be any unfavorable and unintended sign (including a clinically significant laboratory finding), 
symptom, or disease temporally associated with the use of an study drug, whether or not related to 
the study drug. For the purposes of this protocol, all AE occurring during the study are considered 
treatment-emergent AE (TEAE) associated with the use of the product), whether or not the AE is 
determined to be product related. 
According to the FDA Guidance for Industry Adverse Reactions Section of Labeling for Human 
Prescription Drug and Biological Products — Content and Format (January 2006), an adverse 
reaction is an undesirable effect, reasonably associated with the use of a drug, that may occur as 
part of the pharmacological action of the drug or may be unpredictable in its occurrence. This 
definition does not include all adverse events observed during use of a drug, only those for which 
there is some basis to believe there is a causal relationship between the drug and the occurrence of 
the adverse event. Adverse reactions may include signs and symptoms, changes in laboratory 
parameters, and changes in other measures of critical body function, such as vital signs and ECG. 
7.1.2 
Definition of Serious Adverse Events (SAE) 
All AE must be evaluated as potential serious adverse events (SAE). An SAE is any untoward 
medical occurrence that at any dose: 
• Results in death; 


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• Is life-threatening (i.e., the subject was at immediate risk of death from the AE as it 
occurred). This does not include an event that, had it occurred in a more severe form or 
was allowed to continue, might have caused death; 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity; 
• Is a congenital anomaly/birth defect (in the child of a subject who was exposed to the study 
drug); or 
• Is a medically important event or reaction: 
 
Events that do not result in death or hospitalization but may, based on appropriate medical 
judgment, jeopardize the subject or require intervention to prevent one of the outcomes in the 
definition of SAE listed above, should also be considered SAE. 
7.2 
Classification of an Adverse Event 
7.2.1 
Severity of Event 
The Investigator will assess the severity of AE according to the criteria below: 
• Mild: The AE is transient and does not interfere significantly with the subject’s normal 
functioning level. The AE resolves spontaneously or may require minimal therapeutic 
intervention. 
• Moderate: The AE produces limited functional impairment and may require therapeutic 
intervention. The AE produces no sequelae. 
• Severe: The AE results in significant impairment of function and may lead to temporary 
inability to resume the subject’s normal life pattern. The AE produces sequelae which 
require prolonged therapeutic intervention. 
• Life Threatening: The AE results in life-threatening consequences, urgent intervention is 
indicated, urgent operative intervention is indicated or the patient is at risk of death at the 
time of the event if immediate intervention is not undertaken.  
• Fatal: The AE results in death. 
 
Further, toxicities will be evaluated according to the current NCI CTCAE (version 4.0) criteria. 
7.2.2 
Relationship to Study Agent 
The following five-point scale will be used by the Investigator to rate the relationship of the AE to 
the study product: 
 
• Definitely related: A clinical event (including laboratory test abnormality) occurring in a 
plausible time relationship to drug administration, and which cannot be explained by 
concurrent disease or other drugs or chemicals. The response to withdrawal of the drug 


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(de-challenge) should be clinically plausible. The event must be definitively associated 
pharmacologically, using a satisfactory re-challenge procedure, if necessary. 
• Probably related: A clinical event (including laboratory test abnormality) with a 
reasonable time sequence to administration of the drug, unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and which follows a clinically reasonable 
response on withdrawal (de-challenge). Re-challenge information is not required to fulfill 
this definition. 
• Possibly related: A clinical event (including laboratory test abnormality) with a reasonable 
time sequence to administration of the drug, but which could also be explained by 
concurrent disease or other drugs or chemicals. Information on drug withdrawal may be 
lacking or unclear. 
• Unlikely to be related: A clinical event (including laboratory test abnormality) whose 
temporal relationship to drug administration makes a causal relationship improbable (e.g., 
the event did not occur within a reasonable time after administration of the trial medication) 
and in which other drugs or chemicals or underlying disease provides plausible 
explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• Not related: An event for which sufficient information exists to conclude that the etiology 
of the event is unrelated to the study drug. An alternative definitive etiology should be 
documented by the Investigator. 
 
Causality will be assessed as follows: 
The Investigators will assign causality at their respective sites during the study. The SMC 
will review the assigned causality for all AE and SAE prior to database lock. This 
assignment will be included in the study database and final study report. As noted in the 
FDA Guidance for Industry Adverse Reactions Section of Labeling for Human 
Prescription Drug and Biological Products — Content and Format, decisions on whether 
there is some basis to believe there is a causal relationship will be based on factors such as: 
(1) the frequency of reporting, (2) whether the adverse event rate for the drug exceeds the 
placebo rate, (3) the extent of dose-response, (4) the extent to which the adverse event is 
consistent with the pharmacology of the drug, (5) the timing of the event relative to the 
time of drug exposure, (6) existence of challenge and de-challenge experience, and (7) 
whether the adverse event is known to be caused by related drugs. 
7.2.3 
Expectedness  
Expected adverse reactions are AE that are common and known to occur for the study agent being 
studied. Expectedness refers to the awareness of AE previously observed, not on the basis of what 
might be anticipated from the properties of the study agent. 
An AE or suspected adverse reaction is considered "unexpected" if it is not listed in the 
Investigator’s Brochure (IB) or is not listed at the specificity or severity that has been observed; 
or is not consistent with the risk information described in the general investigational plan or 


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elsewhere in the protocol, as amended. "Unexpected," as used in this definition, also refers to AE 
or suspected adverse reactions that are mentioned in the IB as occurring with the class of drugs or 
as anticipated from the pharmacological properties of the drug, but are not specifically mentioned 
as occurring with the particular drug under investigation. 
The Medical Monitor and sponsor’s Medical Director will be responsible for determining whether 
an AE is expected or unexpected.  
7.3 
Time Period and Frequency for Event Assessment and Follow-Up 
The Investigator will record all reportable events with start dates occurring any time after first 
study drug dose application until 30 days after the last study drug application for AE or, in the case 
of an SAE, at least 30 days after onset, whichever is later. At each study visit, the investigator will 
inquire about the occurrence of AE/SAE since the last visit. Events will be followed for outcome 
until resolution or stabilization. 
7.4 
Reporting Procedures 
7.4.1 
Adverse Event Reporting  
AE will be captured from first study drug dose application until 30 days after the last treatment 
application. The occurrence of an AE or SAE may come to the attention of study personnel during 
study visits and interviews of a study participant presenting for medical care, or upon review by a 
study monitor. All AE including local and systemic reactions not meeting the criteria for SAE will 
be captured on the appropriate eCRF. If the subject reports several signs or symptoms, which 
represent a single syndrome or diagnosis, the latter should be recorded in the eCRF.  
Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to 
make a diagnosis), and time of resolution/stabilization of the event. All AE occurring while on 
study must be documented appropriately regardless of relationship. All AE will be followed to 
adequate resolution. 
Any medical condition that is present at the time that the participant is screened until just prior to 
the first study drug application will be considered as baseline medical history condition and not 
reported as an AE. However, if the study participant’s condition deteriorates at any time during 
the study, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AE characterized as intermittent require 
documentation of onset and duration of each episode. 
Clinically significant laboratory abnormalities will be recorded as adverse events. Clinically 
significant laboratory abnormalities are those that are changed compared to baseline and require 
intervention, whether or not they are associated with signs or symptoms. 


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7.4.2 
Serious Adverse Event Reporting  
The study clinician will complete a SAE Form within the following timelines: 
• All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the SAE Form and submitted to the Sponsor within 24 hours of site awareness.  
• Other SAE regardless of relationship, will be submitted to the Sponsor within 72 hours of 
site awareness. 
All SAE will be followed until satisfactory resolution or until the site investigator deems the event 
to be chronic or stable. Other supporting documentation of the event should be provided as soon 
as possible. The Sponsor will be responsible for notifying FDA of any unexpected fatal or life-
threatening suspected adverse reaction as soon as possible but in no case, later than 7 calendar 
days after the sponsor's initial receipt of the information. 
All SAE, including death, due to any cause which occurs during this study between the period of 
dose administration and last study visit, whether or not expected and regardless of relationship to 
study drug, must be reported to the Medical Monitor immediately upon discovery of the event, 
using the SAE reporting form, scanned and sent by email. Additionally, the SAE report form may 
also be submitted to the sponsor by fax. SAE reports should be sent to: 
Dr. Tony Verco 
 
 
 
 
Rose Marie Cavanna-Mast 
Medical Monitor 
 
 
 
 
Director, Clinical Trials  
Email: tony.verco@usbiotest.com  
 
 
Email: rosemarie.cavanna@usbiotest.com  
Phone: 805-235-9193  
 
 
 
Phone: 281-685-6092 
Fax: 805-980-4897  
 
 
 
 
Fax: 805-980-4897 
 
24-hour Emergency Contacts: 
Gere diZerega, MD 
or 
Tony Verco, MD 
 
 
 
 
 
Medical Director 
 
Medical Monitor 
 
 
 
 
 
805-630-2800  
 
805-235-9193 
 
The sponsor will advise the Investigator regarding the nature of any further information or 
documentation that is required. The Investigator should provide the following documentation at 
the time of SAE reporting if available: 
• SAE Report Form; 
• Concomitant and support medication pages; 
• Relevant diagnostic reports; 
• Relevant laboratory reports; 
• Admission Notes; 
• Hospital discharge summary (when available). 


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7.4.3 
Events of Special Interest  
Events of Special Interest will be defined and reported to the authorities by the sponsor as signs of 
local effect and toxicity e.g. odor, purulence, new ulceration at the treatment site, and bleeding. 
Adverse events of special interest usually attributed to paclitaxel include infusion reactions, vital 
signs, and bone marrow depression. Additionally, systemic toxicity due to paclitaxel exposure 
such as reduction in neutrophils (absolute and relative) and thrombocytopenia will be monitored 
by the sponsor. Due to the low total dose administered, very low surface area of cutaneous 
metastases surface exposed relative to body weight and size, and expected absorption rate of 
SOR007, it is unlikely that detectable and clinically relevant systemic levels of SOR007 will occur. 
7.4.4 
Reporting of Pregnancy  
A female subject is considered to be of childbearing potential unless she has had a hysterectomy, 
is at least one year postmenopausal or has undergone tubal ligation. Male patients whose 
vasectomy has been confirmed by negative semen analysis at least 3 months after the vasectomy 
are exempt from using contraceptives. For the purposes of this study, male or female subjects must 
use at least one medically approved and highly effective birth control method (low failure rate (i.e. 
< 1% per year when used consistently and correctly) to include hormonal methods, barrier 
methods, IUD or abstinence. Any contraceptive method or justification for lack of method must 
be recorded in the subject source. 
If any subject becomes pregnant during the study, the subject must be followed up until birth or 
termination of pregnancy. The pregnancy is to be immediately reported to US Biotest on the 
Pregnancy Report form. The anticipated date of birth or termination of the pregnancy should be 
provided at the time of the initial report. The outcome of the pregnancy should be reported to US 
Biotest as soon as it is known on the Pregnancy Report form. If the pregnancy ends for any reason 
before the anticipated date initially reported the Investigator must notify US Biotest the following 
working day. 
If the outcome of the pregnancy meets any criteria for classification as a SAE (including stillbirth, 
neonatal death, spontaneous abortion, or congenital anomaly - including that in an aborted fetus) 
the Investigator must follow the procedures outlined in protocol Section 7.4.2. for reporting SAE. 
Any neonatal death occurring ≤ 30 days after birth will be reported as a SAE. 
7.5 
Study Halting Rules  
This study is a Phase 1/2 dose escalation study, and dose escalation will be determined following 
review of all safety and tolerability data of a cohort by the Medical Monitor in conjunction with 
the SMC.  
The Sponsor is responsible for notifying the FDA of any temporary halts to the study or when a 
study is terminated; the Investigator will be required to notify the IRB accordingly.  


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The severity of toxicity will be classified according to CTCAE criteria (version 4.0). Any 
adverse event that is considered related or possibly related to SOR007 is potentially a DLT. The 
definition of a DLT will be made by consensus by the SMC.  
Dose escalation of SOR007 will be halted when ≥ 2 grade 3 AEs (CTCAE version 4.0), occur in 
any single cohort/dose level and are determined to be “probably related” to SOR007 (See Figure 
2). Further enrollment will be temporarily halted until the safety review has been conducted.  The 
Medical Monitor, in conjunction with the SMC will determine next steps per the Safety Monitoring 
Plan. The final decision for dose escalation and/or premature study drug discontinuation is the 
responsibility of the Medical Monitor.  
7.6 
Dose Escalation and Dose Limiting Toxicity 
During the dose escalation phase, the study will follow a standard 3+3 dose-ascending design, with 
the first cohort of three subjects commencing treatment with 0.15% SOR007. The SMC will 
review all available data on a monthly basis and after the last subject in each cohort of three 
subjects completes 15 days of treatment to determine whether dose escalation may continue, per 
the Safety Monitoring Plan. If no DLTs are identified in any of the first 3 subjects in a cohort, dose 
escalation may proceed. If a single dose limiting toxicity (DLT) is identified in one of three 
subjects in the cohort, a further three subjects will be enrolled at the same dose level. If one or 
more DLT occur in the three additional subjects enrolled in the cohort, dose escalation will stop 
and the prior dose level will be regarded as the Maximum Tolerated Dose (MTD) and taken 
forward into the dose expansion phase. If no further DLTs are identified, dose escalation will 
continue, until either a DLT is identified at a higher dose or the top dose of 2.0% SOR007 is 
reached. During the dose expansion phase the SMC will review all available data on a monthly 
basis until the study is complete. 
If it is determined that a DLT has been reached, the prior dose level will be defined as the highest 
dose with an acceptable safety and tolerability level.   
Figure 2. Dose Escalation and Study Stop Algorithm – Step-by-Step Procedure 
Step 
Regimen 
Outcome 
Outcome 2 
Next Step 
1 
(n=3) 
0.15% BID 
2 DLT 
STOP STUDY 
1 DLT – add 3 subjects 
If 1 further DLT 
STOP STUDY 
If no DLT 
Go to Step 2 (1% BID) 
0 DLT 
Go to Step 2 (1% BID) 
2 
(n=3) 
1% BID 
2 DLT 
Go to Step 4 (0.15% BID) 
1 DLT – add 3 subjects 
If 1 further DLT 
Go to Step 4 (0.15% BID) 
If no DLT 
Go to Step 3 (2% BID) 
0 DLT 
Go to Step 3 (2% BID) 
3 
(n=3) 
2% BID 
2 DLT 
Go to Step 5 (1% BID) 
1 DLT – add 3 subjects 
If 1 further DLT 
Go to Step 5 (1% BID) 
If no DLT 
Go to Step 6 (2% BID) 
0 DLT 
Go to Step 6 (2% BID) 


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Step 
Regimen 
Outcome 
Outcome 2 
Next Step 
4 
0.15% BID 
≥ 3 DLT 
STOP STUDY 
5 
1% BID 
≥ 3 DLT 
STOP STUDY 
6 
2% BID 
≥ 3 DLT 
STOP STUDY 
Dose Limiting Toxicity will be defined as:  
Non-Hematologic: 
• > Grade 3 non-hematological toxicity, excluding nausea, vomiting, diarrhea; 
• > Grade 3  nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/ 
antidiarrheal therapy >72 hours; 
• Any toxicity which in the judgment of the Medical Monitor, Principal Investigator and 
Sponsor Medical Director is considered a DLT; 
• Hypersensitivity reactions to SOR007 that cannot be controlled with standard treatment; 
• New ulceration within the treatment area; 
• ALT or AST >3x ULN and total bilirubin > 2x ULN. 
• Any death not clearly due to the underlying disease or extraneous cause. 
Hematologic: 
• > Grade 3 anemia and/or neutropenia; 
• Neutropenic fever; 
• Thrombocytopenia of any Grade if associated with clinically significant bleeding 
(clinically significant as determined by the Investigator, or results in a transfusion of red 
blood cells.),  
•  Grade 4 thrombocytopenia without bleeding. 
Study Halt Rules: 
• New ulceration within the treatment area occurring in ≥ 2 of 6 subjects in each dose 
escalating cohort, or ≥ 3 of 9 subjects in the dose expansion cohort.  
• Any Grade 4 dermal toxicity 
• ≥ 3 Grade 3 AE occurring in the cohort of 9 subjects, and which are determined to be 
“probably related” to SOR007 (in the dose expansion phase only). 
Dose Expansion Phase: 
In the dose expansion phase, additional subjects will be enrolled to reach a maximum of 16 total 
subjects at the dose level determined to be the MTD in the dose escalation phase. Subjects in the 
dose expansion phase will attend the clinic on the same visit days and receive the same evaluations 
as the dose escalation phase above. 


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7.7 
Safety Oversight 
Safety will be overseen by the SMC, in conjunction with the Medical Monitor. In the event the 
Medical Monitor has any concerns or identifies any safety trends emerging during ongoing reviews 
it will be brought to the immediate attention of the Sponsor Medical Director and the Principal 
Investigator for further discussion and action as required. 
All subject study data will be captured in an EDC system, allowing real-time access to ongoing 
safety and tolerability data. The SMC and the Medical Monitor will review all data for each subject 
entered to the database on a regular basis (in both dose escalation and dose expansion), and upon 
completion of the Day 15 visit of the last subject in a cohort and prior to dose escalation 
proceeding, the Medical Monitor will review the cohort data, and a report will be generated 
outlining any safety concerns from the data available for review in the EDC. This report will be 
shared with the Sponsor Medical Director and Principal Investigator and will take place prior to 
proceeding with dose escalation. 
8 
CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and 
with applicable regulatory requirement(s). 
US Biotest monitors, or monitors designated by US Biotest, will conduct scheduled site visits to 
the investigational centers for the purposes of monitoring the study. The Investigator agrees to 
allow these monitors, and other authorized sponsor personnel or designees, access to the subject’s 
medical records, Investigator Site File (ISF), eCRF, and any other source documents as needed to 
assure the conduct of the study is within compliance. In addition, the FDA or other government 
agencies may request an inspection following notification to the site. In such an event, the 
Investigator agrees to notify the sponsor immediately of the request, and will allow sponsor and 
inspectors to review records. 
US Biotest will conduct a Site Initiation Visit to provide the Investigator and their staff with a 
comprehensive overview of the protocol and study procedures and to review mutual obligations 
and requirements of regulatory authorities prior to any subjects being consented. The Investigator 
Site File (ISF) or regulatory file containing essential and non-essential documentation will be kept 
at the site for reference and inspection. 
Routine monitoring visits will be conducted by the sponsor to assure compliance with the study 
protocol, to review and verify all study documentation is properly maintained to include, but not 
limited to: the subject’s source documents, the eCRF, clinical supplies, all investigational product 
receipt, accountability, storage and disposition records are maintained and to assess the continued 
suitability of the investigational site.  


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Upon completion of the study, the monitor will make a final close out visit to the site to assess 
final conduct of the study, complete a final regulatory review and inventory all clinical drug and 
non-drug supplies for disposition or return to US Biotest or designee. 
9 
STATISTICAL CONSIDERATIONS  
9.1 
Statistical and Analytical Plans 
A formal Statistical Analysis Plan (SAP) will be prepared for this trial, and the SAP will be signed 
off prior to study database lock. 
9.2 
Statistical Hypotheses 
No formal statistical inference (i.e. “p-values”) will be applied.  The results of this trial will be 
based on descriptive statistics only. 
9.3 
Analysis Datasets 
In this safety and tolerability trial, all subjects who are enrolled and receive at least one dose of 
study drug will be included in the descriptive analysis. 
9.3.1 
Missing Data 
Data will be presented as observed and no missing data imputation will be performed.   
9.4 
Description of Statistical Methods 
9.4.1 
General Approach 
The focus of the trial will be on the safety and tolerability of the dose escalated treatments.  The 
general approach will be to highlight any trends that cause concern for the reviewing medical 
monitoring team (i.e. dose limiting toxicities (DLT)). 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) 
Not applicable. The primary objective is to evaluate the safety and tolerability as demonstrated by 
TEAE, changes in laboratory assessments, physical examination findings and vital signs. 
9.4.3 
Analysis of the Secondary Endpoint(s) 
Secondary endpoints will be summarized descriptively.  These will include supportive information 
to provide context for the dose(s) chosen to move forward for future study.   
 
• Objective tumor response, defined as the difference in the sum of the tumor diameter/s 
between baseline and Visit 6; i.e. 14 days after the last dose in the dose escalation and 
expansion phases depending on dose regimen. Tumor surface area and response will be 


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assessed at all visits. Change in surface area will be assessed using ImageJ freeware 
provided by the NIH.  
• Objective Clinical Response is defined as subjects with Complete Clinical Response (CR) 
+ Partial Response (PR), further defined as the percentage of subjects who achieve 
complete clinical response or partial response 14 days after the last treatment with SOR007, 
measured as change in the sum of the longest diameter/s of the target lesion/s 14 days after 
last treatment. The response to treatment is then evaluated as a function of post-treatment 
total diameter divided by pretreatment total diameter.  
• Best overall response is defined as the best response recorded from the start of study 
treatment until the end of the study i.e. Visit 6/Day 43 or Visit 7/Day 70.  
• The definition of eligible cutaneous tumors is based on the (version 1.1) definition of 
measurable tumors (superficial and ≥ 10mm in its longest diameter). Complete clinical 
response (CR) is defined as absence of any detectable residual disease in the target lesion/s; 
partial response (PR) as at least a 30% decrease in the sum of the diameters of the target 
lesion/s compared to baseline (Visit 2); and progressive disease (PD) as at least a 20% 
increase in the sum of diameters of target lesion/s, taking as reference the smallest sum on 
study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. 
Stable disease (SD) is defined as the sum of target lesion diameters between that defined 
as PR or PD. 
• The appearance of new non-target lesions during participation in this study does NOT 
constitute progressive disease. 
• Change in pain (NRS-11) score from baseline to any post-baseline time point that the pain 
scale captures.  
• The concentration of paclitaxel in the systemic circulation post-topical application, will 
be measured by pharmacokinetic (PK) sampling for Group A Subjects on Days 1 (24 
hours post-application), 8, 15, 29 and 43 or for Group B Subjects Days 1 (24 hours post-
application), 8, 15, 29, 57 and 70. If some concentration data is above the detectable limit 
and can be reported numerically, this data will be tabulated and graphed for individuals 
and by dose group.  
9.4.4 
Safety Analyses 
9.4.4.1 
Adverse Events 
Adverse events (AE) recorded during the trial will capture medically relevant changes found 
during the physical exam, and medically relevant changes in vital signs and laboratory analytes 
found during the course of the trial.  In addition, spontaneously reported or observed events will 
be recorded 
Events reported at or after the application of SOR007 will be considered Treatment Emergent 
Adverse Events (TEAE).  All reported events will be listed by subject number and assigned 
treatment, investigator term, MedDRA coded term, date/study day (from initial treatment) for 


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onset and cessation, severity (using the NCIC severity grading), relationship to study medication 
and but only the TEAE will be tabulated.  
Safety analysis for dose escalation will be based on the review of the data from the first 15 days 
of treatment, when a decision is made to proceed to increase the dose or not.  
Adverse event reports will be coded using the most recent version of MedDRA, signed off by the 
Medical Monitor and presented by System Organ Class (SOC) and preferred term.  All AE and 
abnormal laboratory variables will be assessed according to the NCI-CTCAE (version 4.0) grading 
system. The number of subjects and number of events reported will be presented in frequency 
tables (overall, by intensity, by relationship and by outcome) for each dose cohort.  Adverse events 
of special interest (e.g., AE leading to study drug discontinuation, SAE, DLT, deaths) will be 
presented separately.   
9.4.4.2 
Laboratory Analytes 
Quantitative laboratory data will be summarized as mean values and change from baseline scores 
(change = baseline-visit) presented by dose level for each sampling time point.  For tests with 
normal ranges provided, the clinical status and its change from baseline (Normal/High 
Abnormal/Low Abnormal) will be summarized using shift tables for each dose group.  Analytes 
of particular interest (e.g., hematological tests) may be graphed by subject with the dose indicated; 
these special analytes will be confirmed in the SAP. 
9.4.4.3 
Vital Signs 
Vital signs (systolic and diastolic blood pressure, heart rate, respiration rate and temperature) will 
be tabulated and mean raw values and changes from baseline scores (change = baseline-visit) 
where baseline is the last measurement prior to the study drug application, for each treatment 
group. 
9.4.5 
Adherence and Retention Analyses 
All subjects who enter the trial will be accounted for and any reasons for early termination noted 
– including disease progression and AE. 
9.4.6 
Baseline Descriptive Statistics 
Complete demographic and baseline data will be tabulated.  The medical history, which will be 
coded in MedDRA, will be presented.  The disease history data, with a focus on the previous 
treatment and current staging, will be presented in by-subject listing.  Categorical results will be 
summarized. 
9.4.7 
Planned Interim Analyses  
9.4.7.1 
Safety Review 
See Section 7.6. 


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9.4.7.2 
Efficacy Review 
Not applicable. 
9.4.7.3 
Additional Sub-Group Analyses 
Not applicable. 
9.4.8 
Multiple Comparison/Multiplicity 
Not applicable, as no inferential analyses will be employed. 
9.4.9 
Tabulation of Individual Response Data 
All data collected in the eCRF will at a minimum be listed; listings will support the tabulated 
data/outcomes. 
9.4.10 
Concomitant Medication 
All medication taken during the trial will be, at a minimum, listed with the start and stop dates.  
For this small clinical trial, the medications will not be coded using the WHO Drug Dictionary. 
Although no interaction studies have been conducted using SOR007, paclitaxel is metabolized by 
cytochrome P450 isozymes CYP2C8 and CYP3A4 (Taxol Package Insert). Thus, there is a 
potential for drug interactions with concomitantly administered substrates (e.g., repaglinide and 
rosiglitazone), inhibitors (e.g., gemfibrozil), and inducers (e.g., rifampin) of CYP2C8. There is 
also the potential for paclitaxel to interact pharmacokinetically with CYP3A4 substrates (e.g., 
midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), 
inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, 
nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and 
carbamazepine). 
9.5 
Safety Monitoring Committee (SMC) 
The Safety Monitoring Committee (SMC) will draft and agree to a Charter which outlines the 
criteria to be applied to the subjects in the trial as well as the final choice of dose groups to be 
studied further, prior to the first subject being enrolled in the trial. The trial statistician will work 
with the SMC to produce specific data driven reports to support their decision making. 
Subject safety will be the primary driver in all decision making. 
9.6 
Sample Size 
As there are no formal inferential statistical analyses planned, the sample size estimates below 
are provided for informational purposes only to help with decision-making around the cohort 
size and the rarity of events that could be detected. 


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Defining the primary endpoint explicitly requires understanding the primary purpose of the 
study. If, as in this case, the primary purpose of the study is dose-finding, then the incidence of 
DLT would be an appropriate endpoint. When choosing events that will qualify as DLT, it’s 
important to consider the rarity of events given the small number of subjects. For example, if a 
particular adverse event is known to occur in only 5% of subjects, there is a 26.5% chance it will 
appear in a particular cohort of 6 subjects, and a 60.3% chance it will occur during the study of 
22 subjects. If the event only occurs in 1% of patients, there is only a 6% chance it will appear in 
a given 6-subject cohort, and a 16.5% chance it will be observed in the entire study. So rarity is a 
factor that should be considered when deciding which adverse reactions to include as part of the 
endpoint. Estimates were obtained using the “confidence interval for probability of observing a 
rare event” calculation in nQuery 6.01. 
The rationale to expand the final cohort in the Dose Expansion Phase to 16 subjects, from either 
3 or 6 subjects, was based on the “reasonable gain” in detection rate that each additional subject 
would provide in this early phase exploratory trial. The calculations were performed using 
nQuery Advisor 6.01 “confidence interval for probability of observing a rare event”. With 16 
subjects the probability of detecting the 0.1 event rate is 71.8% as well as some probability of 
detecting much rarer events (11.4% probability of detecting an event with a base rate of 0.01, 
and 46% probability of detecting an event with a 0.5 base rate).    
9.7 
Measures to Minimize Bias 
9.7.1 
Enrollment/ Randomization/ Masking Procedures 
Not applicable. 
9.7.2 
Evaluation of Success of Blinding  
Not applicable. 
9.7.3 
Breaking the Study Blind/Participant Code 
Not applicable. 
10 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
confidentiality of participants. Each site will permit authorized representatives of the Sponsor and 
Regulatory Agencies to examine (and when permitted by applicable law, to copy) clinical records 
for the purposes of quality assurance reviews, audits, and evaluation of the study safety, progress, 
and data validity.  
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 


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An eCRF is required and must be completed for each consenting and enrolled subject by qualified 
and authorized study site personnel.  
Subjects who fail the Screening assessments will have demographics and reason for screen fail 
collected.   
Subjects meeting all inclusion/exclusion criteria will have all data entered in an eCRF. All data in 
the eCRF must reflect the corresponding source document. Any corrections to entries made on the 
eCRF must be documented in a valid audit trail. Only data required by the protocol for the purposes 
of the study should be collected within the EDC. 
The Investigator must maintain adequate and accurate source documents on which the eCRF for 
each subject are based. They will be separate and distinct from the eCRF. These records should 
include detailed notes on: 
• The medical history prior to the subject’s involvement in the study; 
• Date of informed consent; 
• The basic identifying information that links the subject’s medical record with the eCRF; 
• The results of all diagnostic tests performed, diagnoses made, therapy provided, and any 
other data on the condition of the subject; 
• The medical condition during the subject’s involvement in the study; 
• All AE; 
• The subject’s exposure to the study medication; 
• The subject’s exposure to any concomitant therapy; 
• All relevant observations and data on the condition of the subject throughout the trial; 
• Justification for all entries in the subject’s eCRF.  
11 
QUALITY ASSURANCE AND QUALITY CONTROL 
Data required by the protocol will be collected and entered into a validated data management 
system that is compliant with all regulatory requirements. The eCRF is an electronic document 
designed to record all of the protocol-required information to be reported to the Sponsor on each 
study subject. 
Data recording must follow the instructions described in the eCRF Completion Guidelines. The PI 
has ultimate responsibility for the collection and reporting of all clinical data entered on the eCRF. 
The PI, as identified on Form FDA 1572, must electronically sign the completed eCRF for each 
participating subject to attest to their accuracy, authenticity, and completeness. 
The EDC application being used in this study is OpenClinica, an open source application which 
has been installed and validated by McDougall Scientific Ltd., following SOPs based on the 


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Systems Development Life Cycle (SDLC) methodology. All personnel using the system will be 
trained and the training documented. All changes to the database are recorded in an audit trail. The 
database will be locked when all open queries have been addressed, all agreed to data is marked 
as source verified, and the PI has signed off on the eCRF contents.  
All software applications used in the collection of data will be properly validated following 
standard computer system validation methods compliant with all regulatory requirements 
12 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
12.1 
Ethical Standard  
The study will be conducted in accordance with the ethical principles of the Declaration of 
Helsinki. The Sponsor and Investigator will comply with their responsibilities as defined in 21 
CFR 312.50-312.70. 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
the Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 
CFR Part 56, and/or the ICH E6. 
12.2 
Institutional Review Board  
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval, in accordance with local legal requirements. It 
is the responsibility of the Investigator to assure that all aspects of the IRB review are conducted 
in accordance with current regulations. US Biotest and the Investigator must inform each other in 
writing that all ethical and legal requirements have been met before the first subject is enrolled in 
the study. Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled. Any amendment to the protocol will require review and approval by the 
IRB before the changes are implemented at the study site. All changes to the consent form will be 
IRB approved; a determination will be made by the IRB regarding whether previously consented 
participants need to be re-consented. 
12.3 
Informed Consent Process  
12.3.1 
Consent and Other Informational Documents Provided to Participants 
Subjects being considered for participation in this study will be provided an Informed Consent 
Form (ICF) to read and sign before being permitted to participate. The ICF will describe the study 
agent and any prior findings from previous studies, it will describe the study procedures including 
the timing of study clinic visits and their responsibilities to adhere to those timelines, any risks 
which may be associated with the study agent or the procedures being carried out in the study, and 
all other items required under 21 CFR part 50.25.  


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Subjects will be required to provide signed consent prior to any study-related procedures being 
carried out. The Investigator is required to document the process for obtaining informed consent 
in the source notes and according to institutional consenting requirements. 
12.3.2 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the patient’s agreeing to participate in the 
study and continues throughout the study subject’s participation. Extensive discussion of risks and 
possible benefits of participation will be provided to the patients and their families. Consent forms 
will be IRB-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the patient and answer any questions that may arise. 
All patients will receive a verbal explanation in terms suited to their comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research subjects. 
Patients will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The patients should have the opportunity to discuss the study with their surrogates 
or think about it prior to agreeing to participate. The subjects may withdraw consent at any time 
throughout the course of the trial. A copy of the informed consent document will be given to the 
subjects for their records. The rights and welfare of the subjects will be protected by emphasizing 
to them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study. 
The Investigator will obtain informed consent from each subject enrolled in the study, in 
accordance with the U.S. Food and Drug Administration (FDA) regulations 21 CFR 50.20 - 50.27 
and the laws and regulations of the state in which the investigation is being conducted. The IRB 
must approve ICF to be used by the Investigator. The Investigator will provide the sponsor with a 
copy of the written approval generated by the IRB or Ethics Committee before the Investigator 
will be permitted to enroll subjects into the study. 
It is the responsibility of the Investigator to ensure that informed consent is obtained from the 
subject before any activity or treatment is undertaken which is not part of routine care. This 
includes, but is not limited to, the performance of diagnostic or therapeutic procedures and the 
administration of the first dose of study medication. Any draft version of the informed consent 
document modified by each site and must be reviewed and approved in writing by US Biotest prior 
to submission to the IRB. 
Should a protocol amendment be made, the subject consent form may be revised to reflect the 
changes of the protocol. If the consent form is revised, it is the responsibility of the Investigator to 
ensure that an amended consent is approved by the IRB and if required by the IRB, signed by all 
subjects currently on study as well as those subsequently entered in the study. 
The Investigator will not perform any investigation specifically required only for the clinical study 
until valid consent has been obtained. The terms of the consent and when it was obtained must 
also be documented in the eCRF. The original, signed informed consent document must be 


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maintained on file at the study site and be made available for review during monitoring visits and 
site audits. 
12.4 
Study Subject and Data Confidentiality  
Study subject’s confidentiality is strictly held in trust by the participating Investigators, their staff, 
the Sponsor, and their agents. This confidentiality includes the testing of study subjects’ biological 
samples (and genetic tests where applicable) in addition to their clinical information relating to 
study participation. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor. 
The study monitor, authorized representatives of the Sponsor, representatives of the IRB and 
applicable government agencies may inspect all documents and records required to be maintained 
by the Investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for any study subject. The clinical study site will permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by local IRB and Institutional regulations. 
Study subjects research data, for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at McDougall Scientific. This will not include the subject’s contact or 
identifying information. Individual study subjects and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by McDougall Scientific research staff will be secured and password protected. 
At the end of the study, all study databases will be de-identified and archived at US Biotest. 
All local legal requirements regarding data protection will be enforced. The anonymity of study 
subjects must be maintained to the extent required by law. Throughout documentation collection 
and evaluation, subjects will be identified on eCRF and other documents submitted to US Biotest 
and McDougall Scientific by their initials, and birth date (if allowed by local institution 
requirements), and their subject number. Subjects will be advised that all study findings will be 
stored and handled in strictest confidence, according to legal requirements, but will be informed 
that authorized research Investigators and agents of the FDA, the NCI, and authorized personnel 
of US Biotest have the right to inspect their medical records. 
12.4.1 
Research Use of Stored Human Samples, Specimens or Data 
Samples and data collected under this protocol are specifically for use in the evaluation and 
analyses being conducted in the study. Samples will not be available for purposes other than 
indicated within this protocol, and no genetic testing will be performed. 


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Access to stored samples will be limited to personnel authorized to have access at the site prior to 
shipping to the laboratories for analysis/assessment. Samples will be stored using codes assigned 
by the Sponsor or as required by the clinical laboratories.  
Samples will only be retained until analysis is complete, following which samples will be disposed 
of according to the laboratory SOP. No samples will be retained for any future use. 
Data will be kept in password-protected computers. Only Investigators and those delegated on the 
Delegation of Authority Log will have access to the samples and data. 
12.5 
Future Use of Stored Specimens  
Not applicable 
13 
DATA HANDLING AND RECORD KEEPING  
13.1 
Data Collection and Management Responsibilities  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data.  
Black or blue ink is required to ensure clarity of reproduced copies. When making changes or 
corrections, the original entry should be crossed out with a single line to not obscure the original 
entry and all changes should be initialed and dated. No source data is to be erased, overwritten. 
Correction fluid or correction tape must not be used on any source documentation.  
Source documents will be maintained for recording data for each participant enrolled in the study. 
Data reported in the eCRF derived from source documents should be consistent with the source 
documents or the discrepancies should be explained and captured in a progress note and 
maintained in the participant’s official electronic study record.  
Clinical data (including AE, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into OpenClinica, a 21 CFR Part 11-compliant data capture 
system provided by MacDougall Scientific. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source documents.  
Data recording must follow the instructions described in the eCRF Completion Guidelines. The 
PI has ultimate responsibility for the collection and reporting of all clinical data entered on the 
eCRF. 
The database will be locked when all outstanding queries have been addressed, all agreed to data 
is marked as source verified, and the PI has signed off on the eCRF contents. 


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13.2 
Study Records Retention  
The Investigator must retain a copy of all study documents in accordance with the FDA or local 
regulations, whichever are the more stringent. 
The Investigator must maintain study documents: 
• For a minimum of two years following the date the marketing application (NDA) is approved 
for the indication for which the drug was investigated for;  
• For a minimum of two years following the release date of the final report, if no marketing 
application is to be filed, or if the marketing application is not approved for the indication of 
which the drug was investigated or is discontinued and the FDA has been notified; or, 
• For a minimum of 15 years after the completion or discontinuation of the study to be filed in 
support of the registration in the European Union. 
• The Investigator, or designee will notify the sponsor in writing if the study records are moved 
or transferred to another responsible individual. 
These documents should be retained for a longer period, however, if required by local regulations. 
No records will be destroyed without the written consent of the sponsor, if applicable. It is the 
responsibility of the sponsor to inform the Investigator when these documents no longer need to 
be retained 
13.3 
Protocol Deviations  
A protocol deviation is any noncompliance with the clinical trial protocol, Good Clinical Practice 
(GCP), FDA or IRB requirements. The noncompliance may be either on the part of the participant, 
the Investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. 
These practices are consistent with ICH E6:  
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 5.1 Quality Assurance and Quality Control, section 5.1.1  
• 5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
It is the responsibility of the site to use continuous vigilance to identify and report deviations as 
soon as possible after occurrence and identification of the protocol deviation. All deviations must 
be addressed in study source documents, reported to the Sponsor and to the data Management 
group.  
Protocol deviations must be reported to the local IRB as per their guidelines. The site PI/study staff 
is responsible for knowing and adhering to their IRB requirements.  
Serious non-compliance on the part of the site, and an inability of the Sponsor to bring the site 
back into compliance, will be reported to the FDA in accordance with their requirements.  


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13.4 
Publication and Data Sharing Policy 
By signing the study protocol, the Investigator agrees with the use of results of the study for the 
purposes of national and international registration, publication, and information for medical and 
pharmaceutical professionals. If necessary, the authorities will be notified of the Investigator's 
name, address, qualifications, and extent of involvement. The sponsor will prepare an integrated 
clinical/statistical report. Publication/presentation of data is not allowed without explicit 
permission from US Biotest. Submission of data for publication/presentation will be coordinated 
and approved by US Biotest in collaboration with the Investigator. 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted 
a clinical trials registration policy as a condition for publication. The ICMJE defines a clinical trial 
as any research project that prospectively assigns human subjects to intervention or concurrent 
comparison or control groups to study the cause-and-effect relationship between a medical 
intervention and a health outcome. Medical interventions include drugs, surgical procedures, 
devices, behavioral treatments, process-of-care changes, and the like. Health outcomes include any 
biomedical or health-related measures obtained in subjects or participants, including 
pharmacokinetic measures and AE. The ICMJE policy, and the Section 801 of the Food and Drug 
Administration Amendments Act of 2007, requires that all clinical trials be registered in a public 
trials registry such as ClinicalTrials.gov, which is sponsored by the National Library of Medicine. 
Data entered to the ClinicalTrials.gov website will be in accordance with the FDA requirements 
for this registration and for publication of study results on that site. 
14 
STUDY ADMINISTRATION 
14.1 
Study Leadership 
The study will be overseen by the Study Manager or designee who will be responsible, together 
with the Investigator, for tracking enrollment, timelines, and deliverables, and other study-related 
performance. 
All questions regarding the enrollment of subjects, regulatory requirements for the conduct of the 
study, safety reporting, or study conduct should be addressed to the Study Manager or Site Monitor 
designated by the sponsor.  
15 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical and therefore any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
have such conflicts managed in a way that is appropriate to their participation in the trial. As 
required by the FDA, a Financial Disclosure Form will be completed by each person noted on the 


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Form FDA 1572 for this study at the site, the original will be filed in the TMF and a copy will 
remain in the site’s regulatory binder. 
16 
LIABILITY AND INSURANCE 
The sponsor will take out reasonable third-party liability insurance coverage in accordance with 
all local legal requirements. This insurance will cover all parties involved in the trial including, 
but not necessarily limited to, the principal Investigator, clinical trial site, and subjects.  
17 
LITERATURE REFERENCES  
Alcaraz I, Cerroni L, Rutten A, Kutzner H, Requena L. Cutaneous metastases from internal 
malignancies: a clinicopathologic and immunohistochemical review. Am J Dermatopathol. 2012; 
34; 347-393. 
Cabula C, Campana LG, Grilz G, Galuppo S, Bussone R, De Meo L, Bonadies A, Curatolo P, De 
Laurentiis M, Renne M, Valpione S, Fabrizio T, Solari N, Guida M, Santoriello A, D’Aiuto M, 
Agresti R. Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a 
multicenter cohort analysis. Ann Surg Oncol. 2015; 22; S442-S450. 
Campana LG, Testori A, Curatolo P, Quaglino P, Mocellin S, Framarini M, Borgognoni L, 
Ascierto PA, Mozillo N, Guida M, Bucher S, Rotunno R, Marenco F, De Salvo GL, De Paoli A, 
Rossi CR, Bonadies A. Treatment efficacy with electrochemotherapy: a multi-institutional 
prospective observational study on 376 patients with superficial tumors. Eur J Surg Oncol. 2016; 
42(12); 1914-1923. 
DeVita VT, Hellman S, Rosenberg SA. (2001). Cancer: Principles and Practice of Oncology 6th 
Edition. Philadelphia, PA; Lippincott Williams & Wilkins. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey, J, Arbuck S, 
Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. 
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). 
European Journal of Cancer. 2009; 45; 228-247. 
Fernández-Antón Martínez, Parra-Blanco V, Avilés Izquierdo JA, Suárez Fernández RM. 
Cutaneous metastases of internal tumors. Actas Dermosifiliogr. 2013; 104(10); 841-853. 
Ma P, Mumper RJ. Paclitaxel nano-delivery systems: a comprehensive review. J Nanomed 
Nanotechnol. 2013; 4(2); 1000164. 
Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. Clinical toxicities 
encountered with paclitaxel (TAXOL). Seminars in Oncology. 1993; 20(4); 1-15. 
Sideras K, Zahasky KM, Kaur JS. Response of cutaneous metastases from breast cancer to 
capecitabine. Clinical Medicine: Oncology. 2008; 2; 415-418. 


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Spratt DE, Gordon Spratt EA, Wu S, DeRosa A, Lee NY, Lacouture ME, Barker CA. Efficacy of 
skin-directed therapy for cutaneous metastases from advanced cancer: a meta-analysis. Journal of 
Clinical Oncology. 2014; 32(28); 3144-3155. 
 

SAP_001.pdf: 
 
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Page 1 of 29 
 
 
US20SOG 
 
31-August-2020 
 
 
STATISTICAL ANALYSIS PLAN (SAP) 
Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of 
Topical SOR007 for Cutaneous Metastases 
 
Protocol 
Number: 
SOR007-2017-01 
Study Phase  
1/2 
Trial Design 
Open-label, multi-center, dose-rising study to evaluate the safety, 
tolerability and preliminary efficacy of three concentrations of SOR007  
Ointment applied topically twice daily for up to 28 days or with the option 
of extending treatment an additional 28 days to total up to 56 days to 
non-melanoma cutaneous metastases. 
Study 
Treatment 
SOR007 (Uncoated Nanoparticulate Paclitaxel) Ointment of three 
concentrations: 0.15%, 1%, and 2% 
Subjects 
Up to 28 subjects, ≥ 18 years of age, with non-melanoma cutaneous 
metastases, from up to 4 sites 
Treatment 
Period and 
Study Duration 
SOR007 ointment (IP) will be applied topically twice daily in Group A 
subjects for up to 28 days and Group B subjects for up to 56 days. 
Follow-up will continue for 30 days after last IP application. The 
participant duration is estimated to be 75 (Group A) or 102 (Group B) 
days for each subject, including the screening period. 
Sponsor 
Contact 
Rose Marie Cavanna-Mast 
US Biotest, Inc.  
231 Bonetti Drive, Suite 240  
San Luis Obispo,  
 
USA CA 93401-7310 
Voice: (805) 595-1300 
Fax: (805) 595-1350 
Email: rosemarie.cavanna@usbiotest.com 
Analysis 
Contact 
Jim Wang 
McDougall Scientific Ltd. 
789 Don Mills Road, Suite 802 
Toronto, Ontario 
Canada M3C 1T5 
 
Voice: (416) 673-9470 
Fax: (416) 424-2095 
Email:jwang@mcdougallscientific.com 
Plan Status  
Final 
 
Plan Date  
Aug 31, 2020 
 


 
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Page 2 of 29 
 
 
US20SOG 
 
31-August-2020 
 
 
SIGNATURE APPROVAL PAGE 
 
Phase 1/2 Dose-Rising, Safety, Tolerability and Efficacy Study of 
Topical SOR007 for Cutaneous Metastases 
 
1 of 2 
Date of Final Protocol 
(including all amendments) 
28-December-2018 (version 7.0) 
05-March-2018 (version 6.0) 
03-October-2017 (version 5.0) 
12-September-2017 (version 4.0) 
10-August-2017 (version 3.0) 
01-August-2017 (version 2.0)  
26-June-2017 (version 1.1)  
21-March-2017 (version 1.0) 
 
 
Date of Final Plan: 31-Aug-2020 
 
I have reviewed the Statistical Analysis Plan.  My signature below confirms my 
agreement with the contents and intent of this document. 
Author: 
 
Jim Wang, MA., P.Stat. (SSC), PStat® (ASA)  
Senior Statistician, McDougall Scientific Ltd. 
 
Reviewed by: 
 
Hong Chen, MSc., P.Stat. (SSC), PStat® (ASA) 
Chief Analytics Officer 
McDougall Scientific Ltd. 
 
 
 
Digitally signed 
by Chungui 
Wang 
Date: 
2020.08.31 
14:51:30 -04'00'
Digitally signed 
by XIAOHONG 
CHEN 
Date: 2020.08.31 
17:09:18 -04'00'




 
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 Table of Contents 
 
 
1 
BACKGROUND ...................................................................................................... 9 
2 
OBJECTIVES ......................................................................................................... 9 
2.1 
Primary Objective ............................................................................................... 9 
2.2 
Secondary Objectives ......................................................................................... 9 
3 
STUDY DESIGN ..................................................................................................... 9 
3.1 
Primary Endpoint .............................................................................................. 10 
3.2 
Secondary Endpoints........................................................................................ 10 
3.3 
Exploratory Endpoint ........................................................................................ 10 
3.4 
Description of the Study Design ........................................................................ 10 
3.5 
Overview of Study Procedures ......................................................................... 12 
3.5.1 
Screening ................................................................................................. 12 
3.5.2 
Baseline (Day 1) ....................................................................................... 12 
3.5.3 
Treatment Visits (Days 8, 16, 29, 57)........................................................ 13 
3.5.4 
End of Study (Day 43/Day 70) .................................................................. 13 
3.5.5 
Safety Follow-up (Final Visit) .................................................................... 14 
3.6 
Schedule of Events .......................................................................................... 15 
3.6.1 Schedule of Events Table 1: Dose Escalation and Dose Expansion Group A: 
28 Days Treatment ..................................................................................... 15 
3.6.2 Schedule of Events Table 2: Dose Expansion Group B: 56 Days Treatment .. 
   ............................................................................................................... 17 
4 
DATA MANAGEMENT METHODS ....................................................................... 19 
4.1 
Data Collection and Database Construction ..................................................... 19 
4.2 
Coding .............................................................................................................. 19 
4.3 
Pharmacokinetic (PK) Data............................................................................... 20 
4.4 
Lesion Measurements ...................................................................................... 20 
4.5 
Tumor Surface Area ......................................................................................... 20 
4.6 
Protocol Deviations ........................................................................................... 20 


 
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5 
STATISTICAL METHODS .................................................................................... 20 
5.1 
Changes from the Protocol ............................................................................... 21 
5.1.1 
PK analysis. .............................................................................................. 21 
5.1.2 
Tumor Response ...................................................................................... 21 
5.2 
Analysis Dataset ............................................................................................... 21 
5.3 
Missing Data ..................................................................................................... 21 
5.4 
Interim Analysis ................................................................................................ 21 
5.5 
Calculated Outcomes ....................................................................................... 21 
5.6 
Analysis Methods ............................................................................................. 24 
6 
RESULTS ............................................................................................................. 24 
6.1 
Study Subjects ................................................................................................. 24 
6.1.1 
Subject Disposition ................................................................................... 24 
6.1.2 
Eligibility ................................................................................................... 24 
6.1.3 
Subject Characteristics ............................................................................. 25 
6.1.3.1 Demographic and Other Baseline Characteristics .......................................... 25 
6.1.3.2 Cutaneous Metastases Diagnosis and Previous Treatment ........................... 25 
6.1.3.3 Medical History ................................................................................................ 25 
6.1.3.4 Physical Examination ...................................................................................... 25 
6.1.4 
Treatment Exposure ................................................................................. 25 
6.2 
Primary Endpoints ............................................................................................ 25 
6.2.1 
Adverse Events ........................................................................................ 26 
6.2.2 
Vital Signs ................................................................................................ 27 
6.2.3 
Clinical Laboratory Measurements ........................................................... 27 
6.3 
Secondary Endpoints........................................................................................ 27 
6.3.1 
Objective Tumor Response ...................................................................... 27 
6.3.2 
Objective Clinical Response ..................................................................... 28 
6.3.3 
Best Overall Response ............................................................................. 28 
6.3.4 
Pain Score ................................................................................................ 28 
6.3.5 
PK Analysis .............................................................................................. 28 


 
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6.4 
Exploratory Endpoints....................................................................................... 28 
6.4.1 
Non-eligible and New Lesions .................................................................. 28 
6.5 
Safety Endpoints .............................................................................................. 29 
6.6 
Other Analyses ................................................................................................. 29 
6.6.1 
Concomitant Medications ......................................................................... 29 
6.6.2 
Pregnancy Test ........................................................................................ 29 
 
LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
AE 
Adverse Event 
APR 
Analysis Programming Requirements 
ATC 
Anatomical Therapeutic Chemical 
BLQ 
Below Limit of Quantitation 
BOR 
Best Overall Response 
CR 
Complete Clinical Response 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DLC 
Data Logic Checks 
DLT 
Dose Limiting Toxicity 
EDC 
Electronic Data Capture System  
LSR 
Local Skin Reaction 
IP 
Investigational Product (SOR007 ointment / Study drug) 


 
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Abbreviation 
Definition 
McDougall 
McDougall Scientific Ltd – CRO contracted to perform the statistical 
programming and analysis functions 
MedDRA 
Medical Dictionary for Regulatory Affairs 
NIH 
National Institutes of Health 
NRS 
Numeric Rating Scale  
PK 
Pharmacokinetic 
PR 
Partial Response 
PT 
Preferred Term 
PD 
Progressive Disease  
OCR 
Objective Clinical Response 
OTR 
Objective Tumor Response 
QOL 
Quality of Life 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SD 
Stable Disease 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SOC 
System Organ Class 
SDLC 
Systems Development Lifecycle 
SOP 
Standard Operating Procedure 


 
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Abbreviation 
Definition 
TEAE 
Treatment Emergent Adverse Event 
WHODD 
World Health Organization Drug Dictionary 
 
 
 


 
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1 
BACKGROUND 
Investigational drug product SOR007 (Uncoated Nanoparticle Paclitaxel) Ointment 
(SOR007) is being developed by NanOlogy, LLC (NanOlogy) for the topical treatment of 
non-melanoma cutaneous metastases. 
Cutaneous metastases occur in up to 10% of cancer patients (excluding melanoma). 
Cutaneous metastases can cause considerable morbidity, leading to infection, bleeding, 
disfigurement and pain. The negative impacts to quality of life (QOL) for this population 
with advanced disease can be devastating.  
Despite the prevalence and impact of cutaneous metastases, a standard of care remains 
elusive. Treatment is complicated by underlying disease, poor patient performance, 
previous radiation therapy and short duration of overall survival. These factors make 
surgery and radiation unfeasible in most patients. Systemic chemotherapy has negligible 
impact on most cutaneous metastases. Additional therapies for cutaneous metastases 
include electrochemotherapy, photodynamic therapy, intralesional therapy, and topical 
therapy.   
SOR007 is being developed as an alternative to existing treatments for cutaneous 
metastases. This Phase 1/2 study will include subjects with non-melanoma cutaneous 
metastases. The study design allows for a safety evaluation of topical application of 
SOR007 as topical therapy for cutaneous metastases. It is expected that topical 
application of SOR007 onto the diseased skin will result in limited systemic exposure. It is 
also anticipated that topical treatment of cutaneous metastases with SOR007 will be well 
tolerated, allowing for repeat administration if necessary. 
2 
OBJECTIVES 
2.1 Primary Objective 
To determine the preliminary safety and tolerability of topical SOR007 Ointment.  
2.2 Secondary Objectives 
x 
To determine preliminary efficacy of topical SOR007; 
x 
To study potential reduction in pain at the treatment area.; 
x 
To describe the pharmacokinetics of topical SOR007 Ointment applied to 
metastatic lesions. 
3 
STUDY DESIGN 


 
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3.1 Primary Endpoint 
Safety and tolerability, as demonstrated by adverse events (AE), changes in laboratory 
assessments, physical examination findings, and vital signs. 
3.2 Secondary Endpoints 
x 
Objective Tumor Response (OTR) - the difference in the lesion size within the 
treatment area between baseline and 14 days after the last dose in the dose group 
i.e. Day 43 for dose escalation subjects, and dose expansion Group A subjects; 
Day 70 for dose expansion Group B subjects; or between baseline and last timor 
assessment for early terminators. Four OTRs will be calculated based on different 
definitions of “lesion size”: 1) Area of the primary eligible lesion, 2) Sum of area of 
all eligible lesions, 3) Longest diameter of the primary eligible lesion, and 4) Sum 
of longest diameter of all eligible lesions. 
x 
Objective Clinical Response (OCR) - subjects with Complete Clinical Response 
(Clinical Response (CR) – the absence of any detectable residual disease in 
eligible lesion(s) within the treatment area) + Partial Response (PR) - at least a 
30% decrease in the lesion size  compared to baseline), within 14 days after the 
last treatment with SOR007 or at the last tumor assessment for early terminators. 
Similar to OTR, four OCRs will be calculated based on different definitions of 
“lesion size”. 
x 
Best Overall Response (BOR) - the best response recorded from the start of study 
treatment until the end of the study (i.e. Day 43 of dose escalation phase subjects 
and dose expansion Group A subjects; Day 70 of dose expansion Group B 
subjects, or early termination visit).  
x 
Change in Pain - Change in pain at the treatment area between Baseline and Day 
43, Day 70 or early termination visit, as measured on the 11-point Numeric Rating 
Scale (NRS). 
3.3 Exploratory Endpoint 
Appearance of new lesions within the treatment area. 
3.4 Description of the Study Design 
This is a phase I/II, open-label, dose-rising study evaluating the safety, tolerability, and 
preliminary efficacy of three concentrations of SOR007 Ointment (0.15%, 1.0%, and 2.0%) 
applied topically to non-melanoma cutaneous metastatic lesions, twice daily for up to 28 
or 56 days. 


 
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The study will include a dose escalation phase and a dose expansion phase. 
In the dose escalation phase, subjects with non-melanoma cutaneous metastases will be 
enrolled in three dose-escalating cohorts consecutively as follows: 
x 
Cohort 1: 0.15% SOR007 (1.23 mg/mL paclitaxel); 
x 
Cohort 2: 1.0% SOR007 (8.2 mg/mL paclitaxel); 
x 
Cohort 3: 2.0% SOR007 (16.4 mg/mL paclitaxel). 
Cohorts will be enrolled sequentially starting at the lowest concentration, i.e. Cohort 1. In 
each cohort, all subjects will be monitored for safety and tolerability. Safety will be 
assessed in an ongoing manner and a Safety Monitoring Committee (SMC) will review all 
available data after the last subject in each cohort of three subjects completes 15 days of 
treatment to determine whether dose escalation may continue.  
Any AE that is considered related or possibly related to SOR007 is potentially a Dose 
Limiting Toxicity (DLT). Specific DLT are described in Section 7.6 of the Protocol. Any 
potential DLT will be discussed and dose escalation will be determined following review of 
all safety and tolerability data of a cohort by the Medical Monitor in conjunction with the 
SMC. The final decision for dose escalation and/or premature termination of the study is 
the responsibility of the Medical Monitor. 
Dose-escalation is applied by using the standard 3+3 dose-ascending method.  For each 
cohort, three subjects are enrolled and are monitored for safety and tolerability after the 
3rd subject in the cohort completes 15 days of treatment: 
x 
If no DLT is found in the three subjects, dose-escalation will continue. 
x 
If one DLT is found in the three subjects, an additional three subjects will be 
enrolled in that cohort.  
o If no additional DLT is found, dose-escalation will continue.  
o If one or more DLTs are found in the three additional subjects, the dose-
escalation will be halted. The dose level of previous cohort will be the Maximum 
Tolerated Dose (MTD) and taken forward into the dose expansion phase. 
x 
If two or more DLTs are found in the first three subjects, dose-escalation will be 
halted. The dose level of previous cohort will be the MTD and taken forward into 
the dose expansion phase. 
x 
The dose-escalation will continue, until either halt rule described above is met or 
the top dose of 2% (i.e. Cohort 3) is reached. 
x 
If no DLT is found in the first three subjects of Cohort 3, or in the additional subjects. 
Dose level 2.0% (of Cohort 3) will be the MTD. 


 
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x 
If dose-escalation is halted at Cohort 1, the study is terminated without the finding 
of MTD. 
In the dose expansion phase, additional subjects will be enrolled to reach a maximum of 
16 total subjects at the MTD found in the dose escalation phase. Subjects in the dose 
expansion phase will receive 28 days (Group A) or 56 days (Group B) of treatment per 
investigator’s decision, subject consent, disease progression, additional systemic 
chemotherapy or other metastatic treatment requirements. 
Group A subjects will attend the clinic on the same visit days and receive the same 
evaluations as the dose escalation phase subjects. Group B subjects will be treated 28 
more days than Group A subjects. Both groups will be followed for 30 days after the last 
IP application. . 
3.5 Overview of Study Procedures 
3.5.1 
Screening 
Within 14 days prior to the first application of investigational product the subject will have 
a medical history and concomitant medication review, demographics, vital signs, pain, and 
cutaneous metastatic lesions assessed and/or measured. Laboratory samples for 
hematology, biochemistry, and urinalysis will be taken and be assessed against 
enrollment criteria.  
All measurable lesions will be measured by caliper and determined to be eligible (RECIST 
criteria ı 10mm in its longest diameter) within the 50 cm2 treatment area selected by the 
Investigator. There will be at least one eligible lesion within the treatment area of 50 cm2 
for a patient to qualify for the study.The investigator may measure and track more than 
one eligible and/or non-eligible lesion within the 50 cm2 treatment area during the study.  
3.5.2 
Baseline (Day 1) 
At Day 1, prior to the first application of SOR007, hematology, biochemistry, and urinalysis 
results will be reviewed and lesion eligibility will be confirmed (≥ 10mm in its longest 
diameter at baseline).  
All measurable lesions in the 50 cm2 treatment area will be measured by caliper and 
documented for size prior to lesion area cleaning. A subject may have multiple eligible 
lesions (≥ 10 mm) and multiple non-eligible lesions (< 10 mm) at baseline. Only one eligible 
lesion is required for study eligibility. The eligible lesion with the largest demension at 
baseline  will be selected as the primary eligible lesion. 


 
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Medical and concomitant medication history will be reviewed/updated, vitals will be 
measured, photos will be taken of the lesion area and lesion area pain will be assessed,   
SOR007 will be applied topically to a  50 cm2 treatment area (identified by the Investigator). 
The amount of SOR007 that will be applied will be 1 finger-tip unit (FTU), approximately 
0.5g.  The subject will be instructed to self-apply SOR007 twice daily for up to 28 days 
during dose-escalation and for up to 28 days (Group A) or up to 56 days (Group B) during 
dose-expansion. The subject will be given a diary for daily completion to document IP 
application, AE and concomitant medication and will be supplied with the appropriate 
number of tubes until the next study visit. Subjects will return to the clinic 24-hours post 
the first IP application for a PK blood draw. 
3.5.3 
Treatment Visits (Days 8, 16, 29, 57) 
On Days 8, 15, and 29, subjects will return to the clinic for targeted physical exam, 
documentation and photography of lesions, pain assessment, blood sample collection for 
hematology, biochemistry and PK. There will also be a review for changes in medication 
and physical status including possible adverse experiences from the diary review and 
interview. For dose expansion Group B, subjects will return to clinic for treatment and 
assessment on Day 57.  
At each visit, the subject will return the daily diary for dosing compliance review and IP 
accountability purposes, will be given sufficient SOR007 for daily treatment until the next 
visit. The subject will be instructed to return SOR007 ointment tubes when empty or per 
institution requirements. At returns, SOR007 ointment tubes will be weighed to assess 
proper and sufficient IP usage. At each visit, the application area will be verified and 
outlined in permanent marker, if necessary. SOR007 ointment  application will be 
supervised by study staff to ensure adequate FTU is appied and is within the 50 cm2-
marked area. Subjects will self-apply the last dose of SOR007 at home the evening of Day 
28 or Day 56. 
The subject will be given a diary for daily completion to document AE and concomitant 
medication at visit 5/Day 29 (Group A) and visit 6/Day 57 (Group B) for return at the end 
of study visits (Days 43/70 respectively).  
3.5.4 
End of Study (Day 43/Day 70) 
After completing the Treatment Period, subjects will enter a 14 day follow-up period and 
return to the clinic on Day 43 (Group A) or Day 70 (Group B) to complete the end-of-study 
evaluations which will include documentation and photography of lesions, targeted 
physical exam, pain assessment, blood sample collection for hematology, biochemistry, 


 
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PK and urinalysis collection. There will also be a review for changes in medication and 
physical status including possible adverse experiences.  
The subject will return all treatment diaries (if not already done so) and the  Day 29-43 
(Group A) or Day 57-70 (Group B) AE diaries and any remaining SOR007 ointment tubes 
(if not previously done so). 
 
3.5.5 
Safety Follow-up (Final Visit) 
A safety visit or phone call will be completed 30 days after the last IP application to review 
AE; the investigator will determine whether this final safety visit is conducted at the clinic 
or over the phone.  
 


 
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3.6 Schedule of Events  
3.6.1 
Schedule of Events Table 1: Dose Escalation and Dose Expansion Group A: 28 Days Treatment 
Timepoint/Study Visit 
Screening  
( < 14 days) 
Baseline 
Treatment 
Follow up 
Visit 1 
(Days -13 to Day 0) 
Day 1 / 
Visit 2 
Day 8 /Visit 3 
(+/- 1 d) 
Day 15 / Visit 4 
(+/- 1 d) 
Day 29 / Visit 5 
(+ 2 d) 
Day 43 /  
Visit 6  (+/- 2 d) 
Day 59 /  
Visit 7 (+ 2 d)  
Informed Consent 
X 
 
 
 
 
 
 
History and Demographics1 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X2 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
 
Vital Signs4 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Status  
X 
 
 
 
 
 
 
Hematology and Chemistry 
X 
 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
 
Pharmacokinetic (PK) Assay5 
 
X 
X 
X 
X 
X 
 
Pain Assessment (NRS-11) 
X 
X 
X 
X 
X 
X 
 
Tumor Measurements6 
X 
X 
 
 
 
 
 
Tumor Assessments7 
 
 
X 
X 
X 
X 
 
Photography 
 
X 
X 
X 
X 
X 
 
Distribute SOR007 Tube(s) 
 
X 
X 
X 
 
 
 
Collect SOR007 Tube(s) 
 
 
X 
X 
X 
 
 
SOR007 Application Training8 
 
X 
X 
X 
 
 
 
SOR007 Application8 
 
X 
X 
X 
 
 
 
Adverse Events9 
X 
X 
X 
X 
X 
X 
X11 
Concomitant Therapy 
X 
X 
X  
X 
X  
X 
 
Diary Distribution10 
 
X 
X 
X 
X 
 
 
Diary Collection 
 
 
X 
X 
X 
X 
 
 
 


 
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1  History includes all medical and surgical events prior to SOR007 treatment application. 
2  Final determination of study eligibility to be confirmed prior to first study drug application. 
3  A comprehensive physical examination to be completed at the screening visit; problem-oriented physical exam to be completed at all other visits as needed. 
4  Vital signs include: blood pressure, heart rate, respiration rate and temperature. 
5  PK samples will be collected 24 hours (+/- 2 hours) post the first study drug application; at Visits 3 and 4 (prior to the first daily application); at Visit 5 and 
Visit 6 (at any time during the visit). 
6  Cutaneous metastatic lesions will be measured with calipers at Screening to determine eligibility and at Baseline to document starting dimensions if different 
from screening. Eligible lesions will be determined by the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest diameter). 
7 Lesions identified at Baseline, will be observed, tracked and documented for changes on a Lesion tracking log by the investigator at each visit. 
8 SOR007 will be administered by topical application to metastatic lesions by the Subject following training by the Investigator or delegated study staff. 
Assigned SOR007 cohort dose will be applied daily on Day 1 to Day 28. 
9 All adverse events and treatment emergent adverse event (TEAE) determination will start immediately following initiation of study treatment. 
10  Subject Diary to be completed daily as an ointment dose application self-reminder and to record all ointment dose applications, record AEs and CMs. 
11 Final safety assessment to be performed 30 days (+ 2 days) after last study drug dose. The decision to conduct the visit in clinic or by phone is at the 
investigator discretion. 
 
 


 
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3.6.2 
Schedule of Events Table 2: Dose Expansion Group B: 56 Days Treatment 
Timepoint/Study Visit 
Screening  
( < 14 days) 
Baseline 
Treatment 
Follow up 
Visit 1 
(Days -13 to 0) 
Day 1 / 
Visit 2 
Day 8 /Visit 3 
(+/- 1 d) 
Day 15 / Visit 4 
(+/- 1 d) 
Day 29 / Visit 5 
(+/- 2 d) 
Day 57 / Visit 6 
(+ 2/- d) 
Day 70 /  
Visit 7  (+/- 2 d) 
Day 86 /  
Visit 8 (+ 2 d)  
Informed Consent 
X 
 
 
 
 
 
 
 
History and Demographics1 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X2 
 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
 
 
Physical Examination3 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signs4 
X 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Status  
X 
 
 
 
 
 
 
 
Hematology and Chemistry 
X 
 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
Pharmacokinetic (PK) 
Assay5 
 
X5 
X 
X 
X 
X 
X 
 
Pain Assessment (NRS-11) 
X 
X 
X 
X 
X 
X 
X 
 
Tumor Measurements6 
X 
X 
 
 
 
 
 
 
Tumor Assessments7 
 
 
X 
X 
X 
X 
X 
 
Photography 
 
X 
X 
X 
X 
X 
X 
 
Distribute SOR007 Tube(s) 
 
X 
X 
X 
X 
 
 
 
Collect SOR007 Tube(s) 
 
 
X 
X 
X 
X 
 
 
SOR007 Application 
Training8 
 
X 
X 
X 
X 
 
 
 
SOR007 Application8 
 
X 
X 
X 
X 
 
 
 
Adverse Events9 
X 
X 
X 
X 
X 
X 
X 
X11 
Concomitant Therapy 
X 
X 
X  
X 
X  
X  
X 
 
Diary Distribution10 
 
X 
X 
X 
X 
X 
 
 
Diary Collection 
 
 
X 
X 
X 
X 
X 
 
 
 


 
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1  History includes all medical and surgical events prior to SOR007 treatment application. 
2  Final determination of study eligibility to be confirmed prior to first study drug application. 
3  A comprehensive physical examination to be completed at the screening visit; problem-oriented physical exam to be completed at all other visits as needed. 
4  Vital signs include: blood pressure, heart rate, respiration rate and temperature. 
5  PK samples will be collected 24 hours (+/- 2 hours) post the first study drug application; at Visits 3, 4 and 5 (prior to the first daily application); at Visits 6 and 
7 (at any time during the visit). 
6  Cutaneous metastatic lesions will be measured with calipers at Screening to determine eligibility and at Baseline to document starting dimensions if different 
from screening. Eligible lesions will be determined by the RECIST (version 1.1) definition of measurable tumors (≥ 10mm in its longest diameter). 
7 Lesions identified at Baseline, will be observed, tracked and documented for changes on a Lesion tracking log by the investigator at each visit. 
8 SOR007 will be administered by topical application to the metastatic lesions by the Subject following training by the Investigator or delegated study staff. 
Assigned SOR007 cohort dose will be applied daily on Day 1 to Day 56. 
9 All adverse events and treatment emergent adverse event (TEAE) determination will start immediately following initiation of study treatment. 
10  Subject Diary to be completed daily as an ointment dose application self-reminder and to record all ointment dose applications, record AEs and CMs. 
11 The final safety assessment to be performed 30 days (+ 2 days) after last study drug dose application. The decision to conduct the visit in clinic or by phone 
is at the investigator discretion. 
 
 


 
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4 
DATA MANAGEMENT METHODS 
4.1 Data Collection and Database Construction 
Data will be collected at the sites via an electronic data capture (EDC) system.  The study-
specific application will be developed based on the protocol requirements and following 
the full Systems Development Lifecycle (SDLC).  The development and management of 
the trial application, including security and account administration, will adhere to the 
Standard Operating Procedures (SOPs) at McDougall.  All clinical research staff will be 
trained in the use of the application, and the training documented prior to enrolling the first 
subject. 
The application design will, where appropriate, provide choice fields in the form of 
checkboxes, buttons and lists to aid in ensuring high quality standardized data collection.  
In addition, Data Logic Checks (or data Edit Checks) will be built into the application based 
on variable attributes (e.g. value ranges), system logic (e.g. sequential visit dates) and 
variable logic (e.g. onset date must be before cessation date).  Visual review and data 
responses will be overseen by a trained data manager. 
The database will be locked when all the expected data have been entered into the 
application, all query responses have been received and validated, the designated data 
has been noted as monitored in the system and each investigator has signed off the 
casebook for each of their study subjects.  The data coding must be accepted by the 
Sponsor, or the Sponsor delegate, and any Serious Adverse Events (SAEs) reconciled 
with the pharmacovigilance data base working with the Medical Monitor. 
The responsible Data Manager will lock each subject’s data files when all the criteria noted 
above are satisfied for that subject. 
The data management processes are outlined in the project specific Data Management 
Plan; this and all related documentation are on file at McDougall and are identified by the 
project code US20SOG. 
All data activities will be performed on validated computer systems as per 21CRF11 and 
kept under control, according to McDougall’s SOPs.  All programming will be performed 
in Statistical Analysis System (SAS) version 9.4 or higher under the Windows Server 
2012R2 operating system at McDougall Scientific Ltd. in Toronto, Canada. 
4.2 Coding 
Adverse Events (AEs) and Medical History will be coded using Medical Dictionary for 
Regulatory Affairs (MedDRA) version 20.1.   


 
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Concomitant medications will be coded using the most current version of WHODD at the 
beginning of coding, version 2017. 
All coding will be approved by the sponsor prior to data base lock. 
4.3 Pharmacokinetic (PK) Data 
PK analysis will be performed by Covance Laboratories, Inc. Madison, Wisconsin, and will 
be reported separately by a third party and will not be described in this Statistical Analysis 
Plan (SAP). 
4.4 Lesion Measurements 
At screening and baseline (prior to treatment), all measurable lesions’ longest diameter 
within the treatment area are captured by EDC database. 
The following lesion measurements are recorded by investigators and will be provided to 
McDougall in Excel data sheet: 
x 
Lesion length and width – all visits 
x 
Lesion status change from baseline 
x 
Lesion status change from previous visit 
4.5 Tumor Surface Area 
Tumor surface area will be assessed using a calibrated grid measurement system 
(ImageJ, freeware) provided by the NIH.  US Biotest will provide McDougall with calculated 
tumor surface area and tumor dimensions in excel data sheet before database lock. 
At each visit, lesions may be measured multiple times (area and/or dimensions) and 
verified in duplicate. The average value will be used in the calculation of tumor responses: 
OTR, OCR, and BOR.  
4.6 Protocol Deviations 
Protocol deviations will be provided in Excel data sheet by US Biotest before database 
lock. 
5 
STATISTICAL METHODS 


 
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5.1 Changes from the Protocol 
5.1.1 
PK analysis. 
PK parameters Cmax, Tmax and AUC was described in the Protocol Section 3.3. 
According to Sponsor’s decision, PK analysis will be performed and reported separately 
by a third party and will not be covered in this SAP. 
All concentrations of paclitaxel will be listed. 
5.1.2 
Tumor Response  
In the Protocol, OTR was defined as the difference in the sum of eligible tumor diameter(s) 
between baseline and Day 43 or 70 (i.e. 14 days after the last dose in the dose escalation 
and expansion phases depending on dose regimen). 
As requested by the Sponsor, OTR will be calcualted based on four lesion measurements: 
1) Area of the primary eligible lesion, 2) Sum of area of all eligible lesions, 3) Longest 
diameter of the primary eligible lesion, and 4) Sum of longest diameter of all eligible 
lesions. 
To be consistent to OTR, the tumor response CR, PR, Stable disease (SD), or Progressive 
disease (PD) at each visit will also be determined based on these four tumor 
measurements. 
Because of the four types of tumor response at each visit, the OCR and BCR will also be 
calculated using four methods. 
5.2 Analysis Dataset 
There is only one analysis dataset for all statistical analysis. All subjects who received at 
least one dose of study treatment will be included in the analysis dataset. 
5.3 Missing Data 
Missing values will not be imputed. 
5.4 Interim Analysis 
No interim analysis is planned in this study. 
5.5 Calculated Outcomes 
The following are the key endpoints derived from the study data for analysis. Complete 
documentation of the calculations and data manipulation required to go from the clinical 


 
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database to the analysis database are contained in the companion document - the study 
Analysis Programming Requirements (APR).  
Age (yr) = year of consent date – birth year, if consent day is after or the same as birthday, 
or 
= year of consent date – birth year – 1, if consent day is before birthday. 
BMI (kg/cm2) = 10000*weight (kg) / [Height (cm)]2 
Study Day 1 = Date of first study treatment = Date of Visit 2 
Study day of an event = Date of that event – Study Day 1 + 1, if it occurs on or after the 
first study treatment, or  
= Date of that event – Study Day 1, if it occurs before the first study treatment. 
Time in Trial (days) = Date of study completion or discontinuation – Informed consent date 
+ 1 
Time on Treatment (days) = Last dosing day – First dosing day = Last dosing day – Study 
Day 1 + 1 
Dosing Compliance (%) of a period = 100 * Actual Doses / Expected Doses, where 
Expected Doses = 2 x Days of the Period. 
Change of Assessment = Assessment at Baseline – Assessment at Visit, where 
“Assessment” is the measurement or assessment of study endpoints (e.g. 
lesion size, vital signs, lab results, etc.). Baseline is the last non-missing 
assessment prior to first study treatment. 
OTR will be assessed using following four methods: 
x 
The difference of the area of the primary eligible lesion between baseline and last 
measurement 
x 
The difference of the sum of area of all eligible lesions between baseline and last 
measurement 
x 
The difference of the longest diameter of the primary eligible lesion between 
baseline and last measurement  
x 
The difference of the sum of the longest diameter of all eligible lesions between 
baseline and last measurement 
The last measurement is 14 days after the last application in the dose group (i.e. 
Day 43 for dose escalation subjects, and dose expansion Group A subjects; Day 
70 for dose expansion Group B subjects) or the last non-missing assessment for 
the early terminators. Eligible lesions are determined at baseline by the 


 
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RECIST (Vn 1.1) definition of measurable tumors (≥ 10mm in its longest 
diameter). The eligible lesion with longest dimension at baseline is selected as 
the primary eligible lesion. 
CTR is assessed according to tumor size change in the treatment area: 
CR = Absence of any detectable residual disease in the treatment area; 
PR = at least a 30% decrease in lesion size between baseline and visit.  Same as 
OTR, PR will be determined from following four methods: 
o At least a 30% decrease in the area of the primary eligible lesion compared 
to baseline 
o At least a 30% decrease in the sum of area of all eligible lesions within the 
treatment area compared to baseline 
o At least a 30% decrease in the longest dimension of the primary eligible 
lesion compared to baseline 
o At least a 30% decrease in the sum of the longest dimension of all eligible 
lesions within the treatment area compared to baseline 
Progressive Disease (PD) = at least a 20% increase in the lesion size. Similar to PR, 
PD will also be determined from four “lesion size” definitions: 
o At least a 20% increase in the area of the primary eligible lesion compared 
to baseline, and with an absolute increase of at least 25 mm2. 
o At least a 20% increase in the sum of area of all eligible lesions within the 
trestmenat area compared to baseline, and with an absolute increase of 
at least 25 mm2. 
o At least a 20% increase in the longest dimension of the primary eligible 
lesion compared to baseline, and with an absolute increase of at least 5 
mm 
o At least a 20% increase in the sum of the longest dimension of all eligible 
lesions within the trestmenat area compared to baseline, and with an 
absolute increase of at least 5 mm. 
SD = tumor size change between PR and PD. 
Note: for the purpose of this study, and as described in the Protocol, the appearance 
of new non-target lesions does NOT constitute progressive disease.  
OCR = Yes, if CR or PR 


 
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5.6 Analysis Methods 
All calculations described in this SAP will be performed using SAS version 9.4 or higher 
resident on the Windows 2012R2 server at McDougall in Toronto, Canada.  
No inferential analyses are proposed. Safety and efficacy endpoints will be descriptively 
summarized. Continuous data will be summarized via PROC MEANS – number of 
subjects, mean, standard deviation, median and range, while categorical data will be 
presented as counts and percentages (or proportions) via PROC FREQ for the descriptive 
displays.   
6 
RESULTS 
All data collected in the clinical database will be listed by subject and treatment group in 
data listings; the dose escalation and dose expansion phases will be differentiated in the 
listings. The dose expansion Group A and Group B will also be separated because of the 
different treatment/visit structures. The organization of the Tables and Listings will be 
guided by the International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use or ICH E3 – Structure and Content of Clinical Study 
Reports. 
6.1 Study Subjects 
6.1.1 
Subject Disposition 
Each Subject enrolled into the trial will be accounted for. The early terminators will be 
summarized by the primary reason for early withdrawal. Data listings for subject 
disposition and end of study information, including any additional textual reasons where 
applicable, will be provided. 
Throughout the trial summarization, the dose escalation subjects, dose expansion Group 
A subjects, and dose expansion Group B subjects will be presented separately and also 
be combined into the designated dose groups to provide an overall view of any dose 
response criteria. 
Protocol deviations will be presented in by-subject data listing.  
6.1.2 
Eligibility 
The failed eligibility criteria and waiver information, if any, will be listed by subject. 


 
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6.1.3 
Subject Characteristics 
6.1.3.1 
Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be listed for all enrolled subjects using 
standard summary statistics. The summary will include age (years), sex, race, ethnicity, 
height (cm), weight (kg), the calculated BMI, and baseline vital signs (i.e. assessments of 
Baseline Visit, or assessments of Screening Visit if Baseline assessments are missing). 
These variables will be summarized by treatment group.  
6.1.3.2 
Cutaneous Metastases Diagnosis and Previous Treatment 
Cutaneous metastases diagnosis are reported in medical history dataset. No separate 
analysis will be provided.   
Previous treatment of cutaneous metastases are captured in the Prior and Concomitant 
Medications form. No separate table or listing will be provided. 
6.1.3.3 
Medical History 
Medical history will be summarized by MedDRA SOC and PT and will be listed by subject. 
6.1.3.4 
Physical Examination 
Clinically relevant results from the physical examination will be recorded in Medical History 
at screening and baseline and as an adverse experience post the first application of the 
study treatment. 
6.1.4 
Treatment Exposure 
Time in trial and time on treatment will be summarized by treatment group. 
Study drug application information, both at clinical visits and at home via diary, will be 
listed.  
Study drug usage data, including dispensed, returned, and used weight, will be listed by 
tube. Total used amount will be summarized by treatment. 
Dosing compliance of each visit and for whole treatment period will be summarized by 
treatment group. 
6.2 Primary Endpoints 
The primary objective of this study is to evaluate the safety and tolerability of three doses 
of topical SOR007 ointment (0.15%, 1.0% and 2.0%) applied to metastatic lesions on 
subjects diagnosed with non-melanoma cutaneous metastases. The primary endpoints 
include AEs, vital signs, and clinical laboratory results. The focus will be on the AEs as 


 
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these will capture the clinically relevant changes in the vital signs and/or laboratory values.  
The vital signs and laboratory analytes will also be summarized in tables and listings as 
part of the complete Clinical Summary Report. 
6.2.1 
Adverse Events 
All Treatment Emergent Adverse Events (TEAEs) will be summarized according to primary 
SOC and PT based on MedDRA coding. The summaries will focus on the counts of 
subjects and also the number of events, for each SOC and PT.  The presentations will 
separate out and highlight any SAEs (including deaths), and AEs leading to the 
discontinuation of study treatment.  
The summaries for TEAEs will be:  
1. the number and percent of subjects/events for all TEAEs;  
2. the number and percent of subjects/events for all TEAEs by Common Terminology 
Criteria for Adverse Events - CTCAE (version 4.0) toxicity grade; 
3. the number and percent of subjects/events for all TEAEs by relationship to study 
drug;  
4. the number and percent of subjects/events for all TEAEs by outcome;  
5. the number and percent of subjects/events for all SAEs;  
6. the number and percent of subjects/events for all TEAEs with death as outcome;  
7. the number and percent of subjects/events for all TEAEs leading to drug 
withdrawal; 
8. the number and percent of subjects/events for all AEs of Specific Interest. The AEs 
of specific interest include the following:  
a. clinically significant laboratory results as determined by the Investigator 
b. peripheral neuropathy 
c. neutropenia, anemia, thrombocytopenia 
d. any infection, local or systemic 
e. anaphylaxis 
f. cardiovascular AEs 
g. hepatoxicity (AST, ALT, GGT, ALP, bilirubin) 
All AEs will be listed by subject. SAEs and DLTs will be listed separately. 


 
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6.2.2 
Vital Signs 
Vital signs (blood pressures, heart rate, respiration rate, and body temperature) at each 
visit and change from baseline will be summarized for each time point using standard 
summary statistics. Baseline is defined as the last non-missing assessments prior to the 
start of the first study treatment. Change from Baseline is defined as baseline value minus 
value at visit. 
All vital signs data will be listed by subject and time point. 
6.2.3 
Clinical Laboratory Measurements  
All laboratory test results (quantitative results, abnormal status, and clinically significant 
status) of blood chemistry, hematology, and urinalysis will be summarized by visit of 
assessment using standard summary statistics. 
For quantitative laboratory measurements after the study treatment, the laboratory 
measurement summarization will also include the Change from Baseline. Change from 
Baseline is defined as baseline value minus value at visit. 
For tests with normal ranges provided, the clinical status (Normal /High Abnormal /Low 
Abnormal) and its change from baseline will be summarized using shift tables.  
All laboratory data will be listed by subject and visit. The laboratory abnormalities will be 
listed separately.  
6.3 Secondary Endpoints 
To determine the primary efficacy and potential pain reduction, the difference between 
baseline (i.e. last non-missing value prior to first SOR007 treatment) and 14 days after last 
treatment (i.e., Day 43 for dose escalation subjects and dose expansion Group A subjects, 
or Day 70 for dose expansion Group B subjects) or the last assessment of early teminators 
of following secondary endpoints will be analyzed.  
6.3.1 Objective Tumor Response 
Eligible lesion is defined as a lesion within treatment area,  with its longest diameter ≥ 10 
mm at baseline.   
The sizes (longest diameter and lesion area) of the Primary elgible lesion, as well as its 
change from baseline, will be summarized by visit. 
The sum of longest diameter and tumor surface area of all eligible lesions, as well as the 
change from baseline, will be summarized by visit.  


 
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OTR, i.e., the change of lesion size from baseline to End of Study (i.e. Day 43 for dose 
escalation subjects, and dose expansion Group A subjects; Day 70 for dose expansion 
Group B subjects, or last assessment for early terminators) will be summarized separately. 
Please see Section 5.5 regarding  the four types of OTRs based on different definitions of 
“lesion size”. 
All measurements of individual lesions, including longest diameter, length, width, tumor 
surface area, status change from baseline, and status change from previous visit, will be 
listed. 
6.3.2 Objective Clinical Response  
At each visit, four types of clinical tumor response (CR, PR, SD, or PD) will be assessed 
and summarized.  The frequency of OCR at each visit, i.e. subject with CR or PR, will be 
summarized by treatment group.   
The CTR and OCR of whole study, i.e. at End of Study (Day 43 visit for dose escalation 
subjects and dose expansion Group A subjects; or Day 70 visit for dose expansion Group 
B subjects, or the last assessment of early terminotors), will be summarized separately.  
6.3.3 Best Overall Response 
The best response recorded from the start of study treatment until the end of the study  
will be summarized.  
6.3.4 Pain Score 
The pain scores as assessed on the 11-point numerical scale (from 0 – no pain to 10 – 
greatest pain imaginable), i.e. NRS-11, will be summarized as raw values and changes 
from baseline in tables and listings at each visit for each dose group. 
6.3.5 PK Analysis 
The concentrations of paclitaxel will be presented in data listing.  
PK parameters calculation and analysis will be conducted and reported separately by a 
third party.   
6.4 Exploratory Endpoints 
6.4.1 Non-eligible and New Lesions 
Non-eligible lesions within the treatment area (<10 mm in diameter) identified at baseline 
and new measured lesions which develop during the trial will be evaluated as exploratory 
endpoints. Each category will be listed separately. 


 
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6.5 Safety Endpoints 
In this study, all safety analyses will be presented as part of the primary endpoint analysis. 
6.6 Other Analyses 
6.6.1 
Concomitant Medications 
All concomitant medications collected in EDC will be coded based on WHODD and will be 
tabulated by the therapeutic class (ATC level 2) and chemical subgroup (ATC level 4). 
The number and percentage of coded medications and subjects who used medications 
will be presented. 
All medications will be listed. 
6.6.2 
Pregnancy Test 
For female subjects, the pregnancy test information: performed /not performed, date, and 
result, will be listed.