A Phase I/II Study of RV001V, a RhoC Anticancer Vaccine, Against Metastasis From Solid Tumours
Phase: PHASE1
Conditions: Prostate Cancer
Sponsor: RhoVac APS

 
CONFIDENTIAL 
This Clinical Study Protocol contains privileged or confidential information which is the property of the 
Sponsor. Information may not be disclosed to a third party without written authorisation from the 
Sponsor. 
 
 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
 
 
A Phase I/II study of RV001V, a RhoC anticancer vaccine, against metastasis 
from solid tumours 
Study code:  
RhoVac-001 
Study development 
phase: 
Phase I/II 
EudraCT number: 
2016-004189-24 
Investigational 
medicinal product: 
RV001V 
 
 
Indication: 
Cancer, metastatic 
solid tumours 
Version: 
Final, version 3 
Date: 
07 November 2017  
Principal Investigator 
at Phase I Unit:  
Jesper Sonne,  
DanTrials ApS, c/o Copenhagen University Hospital, Bispebjerg 
Zelo Phase I Unit, Building 11B,  
Bispebjerg Bakke 23,  
DK-2400 Copenhagen NV, Denmark 
Investigator: 
Professor Klaus Brasso 
Department of Urology, Rigshospitalet 
Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark 
Sponsor Signatory: 
Jens Kristensen 
RhoVac ApS 
SCION DTU Science Park 
Agern Alle 3 
DK 2970 Hørsholm, Denmark 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 2 of 74 
 
1 
SYNOPSIS 
Name of the Sponsor/Company: 
RhoVac Aps 
Study Code:  
RhoVac-001 
Name of Investigational Medicinal Product: 
RV001 Vaccine 0.1 mg/mL (RV001V) 
EudraCT No.:  
2016-004189-24 
Development Phase of the Study: 
Phase I/II 
Trial under an IND:  
No 
TITLE OF THE STUDY: 
A Phase I/II study of RV001V, a RhoC anticancer vaccine, against metastasis from solid tumours 
OBJECTIVES: 
Primary Objective: 
The primary objective is to evaluate the safety and tolerability of RV001 Vaccine 0.1 mg/mL (RV001V) 
following subcutaneous (s.c.) administrations to patients who have been prostatectomised due to 
prostate cancer. 
Secondary objectives: 
The secondary objective is to investigate RV001V-specific T-cells in treated patients, and thereby the 
immunological response before, during and after vaccination. 
Exploratory endpoints 
The exploratory objectives are to investigate the Prostate-Specific Antigen (PSA) levels both in the 
subgroup of patients with measurable levels at baseline and in patients with no measurable levels at 
baseline, to explore the potential associations between PSA levels and immunological response and to 
preliminarily evaluate the progression-free survival (PFS) and overall survival (OS). 
OVERALL STUDY DESIGN:  
The trial is an open phase I/II first-in-human clinical study for a peptide cancer vaccine. 
Between 10 and 25 patients prostatectomised due to prostate cancer will be enrolled. 
The treatment will consist of a total of 11 s.c. vaccinations with RV001V. The first 6 vaccinations will be 
given every 2 weeks, whereas the remaining 5 vaccinations will be administered with 4 weeks between 
each vaccination. Long term follow-up of immunological response and PSA levels will be performed at 3, 
6, 9, and 12 months after the last vaccination.  
The first three patients will be enrolled sequentially. Patient no 1 will have 2 vaccinations before any 
additional patient can be treated. Provided that no safety concern is observed after safety evaluation of 
the two first vaccinations, Patient no 2 may start vaccination and a new safety readout will be performed 
when Patient no 2 has received 2 vaccinations. Provided no safety concern is observed from the two 
first patients, Patient no 3 may start vaccination. New safety readouts will be performed when all 
3 patients have received at least 2 vaccinations. Provided that no safety concern is observed, three 
additional patients may start vaccinations with their first vaccination taking place on separate days. 
Following a new safety readout, and provided no safety concern is observed, all remaining patients may 
start vaccinations with their first vaccination taking place on separate days. All vaccinations will be 
performed at a Phase I Unit. 
The trial will be terminated if treatment related grade 3, 4 or 5 toxicity in accordance with Common 
Terminology Criteria for Adverse Events (CTCAE) is observed in more than one of the first 6 patients, 
with the exception of fever.  
In case the patient develops disease progression, requiring surgical and/or chemotherapeutic treatment, 
the patient will be discontinued from the study and referred back to his urology/oncology team, from 
which he was referred initially, where treatment will be offered independent of participation in the study.  

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 3 of 74 
 
Name of the Sponsor/Company: 
RhoVac Aps 
Study Code:  
RhoVac-001 
Name of Investigational Medicinal Product: 
RV001 Vaccine 0.1 mg/mL (RV001V) 
EudraCT No.:  
2016-004189-24 
Development Phase of the Study: 
Phase I/II 
Trial under an IND:  
No 
INVESTIGATIONAL MEDICINAL PRODUCT: 
RV001 Vaccine 0.1 mg/mL (RV001V). RV001V consists of the peptide RV001 and the adjuvant 
Montanide ISA 51. 
NUMBER OF PATIENTS: 
At least 10 patients will be enrolled in the trial to fulfil the primary objective. Additional patients, up to a 
total of 25 patients, may be enrolled dependent on analysis of immune related data. 
NUMBER OF STUDY CENTRES: 
There will be one study centre involving two clinics; a phase I unit (Zelo Phase I Unit), approved for first-
in-man trials, will be responsible for the conduct of the treatment located at the premise of Bispebjerg 
hospital. The principal investigator will be based at this clinic. The second clinic is located at a nearby 
hospital (Rigshospitalet). The investigator(s) based at Rigshospitalet will be responsible for recruitment 
and consenting patients to the trial. This clinic at Rigshospitalet will follow the patients throughout the 
study and, according to their normal practise, evaluate PSA values sampled at the Phase I Unit and 
provide assessment of the patients’ cancer status. 
MAIN INCLUSION AND EXCLUSION CRITERIA:  
Inclusion criteria 
The patients have to meet all of the following criteria to be eligible to enter the study: 
1) Patients prostatectomised (PT) due to histologically verified adenocarcinoma of the prostate gland 
who currently are not being treated, or expected within the next 8 months to be treated, with any 
anti-cancer treatment. Patients may or may not have measurable PSA. 
2) Able to understand the study procedures and willing to provide informed consent. 
3) Able and willing to comply with study requirements and complete all visits. 
4) Using adequate contraceptive measures. 
All non-vasectomized patients must use condoms during the study and for one month after the last 
vaccination with RV001V, or have a female partner who either has been post-menopausal for more 
than one year or is using a highly effective method of contraception (i.e., a method with less than 1% 
failure rate). 
5) Aged 18 years and above. 
6) ECOG performance status 0 or 1. 
7) Recovered/stabilized at grade ≤2 from all toxicities related to prior treatment(s) in accordance with 
CTCAE. 
8) Laboratory values obtained ≤30 days prior to first vaccination, and more than 3 weeks after potential 
chemotherapy. 
a) Haemoglobin ≥5.6 mmol/L. 
b) Absolute granulocyte count ≥1.5 x 109 /L. 
c) Platelets ≥100 x 109 /L. 
d) Total bilirubin ≤1.5 x upper limit of normal (ULN). 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 4 of 74 
 
Name of the Sponsor/Company: 
RhoVac Aps 
Study Code:  
RhoVac-001 
Name of Investigational Medicinal Product: 
RV001 Vaccine 0.1 mg/mL (RV001V) 
EudraCT No.:  
2016-004189-24 
Development Phase of the Study: 
Phase I/II 
Trial under an IND:  
No 
e) Creatinine ≤1.5 x ULN. 
f) 
Alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and alkaline 
phosphatase (ALP) ≤2.5 x ULN.  
Exclusion criteria 
Patients meeting any of the following criteria will not be permitted to enter the study: 
1) Patient is a candidate for relevant therapies that are the current standard of care for their cancer 
disease. 
2) Patient has been treated with Androgen Deprivation Therapy (ADT), or expected to receive such 
treatment within the next 8 months from enrolment. 
3) Concurrent chemotherapy or radiotherapy within 12 weeks of 1st vaccination, or expected to receive 
such treatment within the next 8 months from enrolment. 
4) Patients have undergone major surgery or have had major bleeding within the last month prior to the 
first vaccination. 
5) Patients with brain or leptomeningeal metastases. 
6) Prior treatment with any therapeutic cancer vaccine(s). 
7) History of second malignancy (except for adequately managed basal cell carcinoma and squamous 
cell carcinoma of the skin). 
8) Patients in need of or treated the last 30 days before the first vaccination with systemic steroids or 
other immune suppressive therapy. Use of inhaled steroids, nasal sprays, and topical creams for 
small body areas is allowed. 
9) History of alcohol or substance abuse within the last 5 years  
10) History of acquired immune deficiency syndrome or positive serological test for human 
immunodeficiency virus infection. 
11) History of viral hepatitis B as determined by positive antibody immunoglobulin M (IgM) to core 
antigen for hepatitis B or positive for hepatitis B surface antigen, or viral hepatitis C as determined 
by positive antibody for hepatitis C. 
12) Participation in any investigational trial or use of any investigational drug(s) within 30 days prior to 
inclusion in this trial. 
13) Any known serious infections, e.g. tuberculosis. 
14) History of significant autoimmune disease such as: Inflammatory bowel disease, Systemic lupus 
erythematosus, Ankylosing spondylitis, Scleroderma, Multiple sclerosis. 
15) Severe medical conditions, such as but not limited to severe asthma/chronic obstructive pulmonary 
disease (COPD), New York Heart Association (NYHA) grading 3 or above, poorly regulated insulin 
dependent diabetes, any significant organ damage as judged by the Investigator. 
16) Other medications or conditions that in the Investigator's opinion would contraindicate study 
participation for safety reasons or interfere with the interpretation of study results 
17) History of drug allergies or known allergy/hypersensitivity to Montanide ISA 51, or intolerance to 
subcutaneous injection. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 5 of 74 
 
Name of the Sponsor/Company: 
RhoVac Aps 
Study Code:  
RhoVac-001 
Name of Investigational Medicinal Product: 
RV001 Vaccine 0.1 mg/mL (RV001V) 
EudraCT No.:  
2016-004189-24 
Development Phase of the Study: 
Phase I/II 
Trial under an IND:  
No 
EFFICACY AND SAFETY VARIABLES:  
Primary endpoint 
The primary endpoint of the study is the proportion of patients developing treatment related grade 3, 4 or 
5 toxicity in accordance with CTCAE, with the exception of fever. The study will be terminated if this 
toxicity is observed in more than 1 of the first 6 patients, i.e. in ≥33.3% of the patients. The study will be 
considered meeting the primary endpoint if the proportion of patients with this toxicity at the end of the 
study is not higher than 33.3%. 
In addition, the tolerability will be evaluated by number of patients who discontinue the study treatment 
prematurely. The safety will be evaluated with frequency and severity of adverse events (AEs). The 
numbers and proportions of patients with any treatment-emergent adverse event, and any serious 
treatment-emergent adverse event will be summarised. Furthermore, changes in vital signs, laboratory 
variables and electrocardiogram (ECG) will be evaluated. 
Secondary endpoints 
For the evaluation of immunological response of the vaccine, the immunogenicity of RV001V in patients 
is determined by measuring anti-vaccine T cells before, during and after vaccination, and by evaluating 
the changes from baseline (last assessment before the first vaccination) to each vaccination and follow-
up visit. 
Exploratory endpoints 
The PSA levels will be evaluated by: 
- 
Changes from baseline in the PSA levels among the patients with measurable levels at baseline 
(the last PSA assessment before the first vaccination) 
- 
Number of patients with measurable PSA levels at baseline and at each vaccination and follow-
up visit. 
The potential association between the PSA levels and immunological response will be evaluated by: 
- 
Anti-vaccine T cell levels classified by the PSA status (measurable or non-measurable) at 
baseline and at each vaccination and follow-up visit 
- 
Correlation of changes from baseline in anti-vaccine T cell levels and PSA levels among the 
patients with measurable PSA levels at baseline. 
The PFS and OS will be evaluated as time from baseline (time of the first vaccination) to the event. For 
PFS, disease progression or death for any reason will be defined as an event. For OS, death for any 
reason is defined as an event. The data from the patients without an event will be censored at the last 
time when the patient is known to be free of disease progression or alive. 
STATISTICAL METHODS:  
All patients who received at least one vaccination will be included in the statistical analyses. A subset 
analysis will be done among the patients who received 3, 6 vaccinations and all 11 vaccinations. 
The data will primarily be analysed with descriptive statistics. For the analysis of changes from baseline, 
the last assessment before the first vaccination will be used as the baseline. For the continuous 
endpoints, the changes from baseline may be estimated using appropriate statistical methods, e.g. 
Mixed Model for Repeated Measures (MMRM) in addition to the descriptive statistics. The time-to-event 
endpoints will be summarized using the Kaplan-Meier method. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 6 of 74 
 
Name of the Sponsor/Company: 
RhoVac Aps 
Study Code:  
RhoVac-001 
Name of Investigational Medicinal Product: 
RV001 Vaccine 0.1 mg/mL (RV001V) 
EudraCT No.:  
2016-004189-24 
Development Phase of the Study: 
Phase I/II 
Trial under an IND:  
No 
STUDY PERIOD: 
The duration of the study is expected to be approximately 2 years, beginning with first patient first visit 
which is anticipated to occur in Q1 2017, and ending with last patient last follow up visit in Q1 2019. All 
patients are expected to be enrolled and have completed vaccine treatment during the first year. The 
second year will consist of follow-up visits. The actual overall study duration will depend on the time 
required to screen and enrol patients, the number of patients needed, and whether patients complete all 
treatment and follow up visits. 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 7 of 74 
 
2 
TABLE OF CONTENTS 
Section 
Page 
1 
SYNOPSIS .................................................................................................................... 2 
2 
TABLE OF CONTENTS ................................................................................................ 7 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ....................................... 10 
3.1 
List of Abbreviations ........................................................................................ 10 
3.2 
Definition of Terms........................................................................................... 11 
4 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ............................ 12 
5 
INTRODUCTION ......................................................................................................... 14 
5.1 
Background ...................................................................................................... 14 
5.1.1 
Cancer Vaccination Therapy ............................................................ 14 
5.1.2 
RhoC as a Vaccine Target ............................................................... 14 
5.1.3 
RV001 .............................................................................................. 15 
5.1.4 
Adjuvant ........................................................................................... 15 
5.2 
Study Rationale ................................................................................................ 15 
5.3 
Potential Risks and Benefits ........................................................................... 16 
6 
STUDY OBJECTIVES ................................................................................................ 18 
6.1 
Primary Objective ............................................................................................. 18 
6.2 
Secondary Objectives ...................................................................................... 18 
6.3 
Exploratory Objectives .................................................................................... 18 
7 
INVESTIGATIONAL PLAN ......................................................................................... 19 
7.1 
Study Design and Plan Description ................................................................ 19 
7.1.1 
Interim Safety Evaluation ................................................................. 20 
7.2 
Study Procedures ............................................................................................ 22 
7.2.1 
Schedule of Study Events ................................................................ 22 
7.2.1.1 
Visit 1a and Visit 1b (Screening Visit, Day -30 to -1) at 
Rigshospitalet and Zelo Phase I Unit ............................................... 22 
7.2.1.2 
Visit 2 (Day 1), at Zelo Phase I Unit ................................................. 23 
7.2.1.3 
Visit 3 (Day 15±2) at Zelo Phase I Unit ............................................ 23 
7.2.1.4 
Visit 4 (Day 29±2), at Zelo Phase I Unit............................................ 24 
7.2.1.5 
Visit 5 (Day 43±5), at Zelo Phase I Unit............................................ 24 
7.2.1.6 
Visit 6 (Day 57±5), at Zelo Phase I Unit............................................ 25 
7.2.1.7 
Visit 7 (Day 71±5), at Zelo Phase I Unit............................................ 25 
7.2.1.8 
Visit 8 (Day 101±7), at Zelo Phase I Unit .......................................... 25 
7.2.1.9 
Visit 9 (Day 131±7), at Zelo Phase I Unit .......................................... 26 
7.2.1.10 
Visit 10 (Day161±7), at Zelo Phase I Unit ......................................... 26 
7.2.1.11 
Visit 11 (Day 191±7), at Zelo Phase I Unit ........................................ 27 
7.2.1.12 
Visit 12 (Day 221±7), at Zelo Phase I Unit ........................................ 27 
7.2.1.13 
Visit 13 (Day 251±14), End of Treatment Follow Up (30 days After 
Last Vaccination), at Zelo Phase I Unit ............................................ 28 
7.2.1.14 
Visit 14 (3 months) Long Term Follow Up Post Last Dose, at Zelo 
Phase I Unit ..................................................................................... 28 
7.2.1.15 
Visit 15 (6 months), Long Term Follow Up Post Last Dose, at Zelo 
Phase I Unit ..................................................................................... 29 
7.2.1.16 
Visit 16 (9 months), Long Term Follow Up Post Last Dose, at Zelo 
Phase I Unit ..................................................................................... 29 
7.2.1.17 
Visit 17 (12 months) Long Term Follow Up Post Last Dose, at Zelo 
Phase I Unit ..................................................................................... 29 
7.2.2 
Study Flow Chart ............................................................................. 30 
7.3 
Discussion of Study Design, Including the Choice of Control Groups ........ 33 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 8 of 74 
 
7.4 
Study Period ..................................................................................................... 33 
7.5 
End of Study ..................................................................................................... 33 
8 
SELECTION OF STUDY POPULATION ..................................................................... 34 
8.1 
Number of Patients .......................................................................................... 34 
8.1.1 
Recruitment ..................................................................................... 34 
8.2 
Inclusion Criteria .............................................................................................. 34 
8.3 
Exclusion Criteria ............................................................................................. 35 
8.4 
Restrictions ...................................................................................................... 35 
8.5 
Removal of Patients from Therapy or Assessment ....................................... 36 
8.5.1 
Withdrawal from Study ..................................................................... 36 
8.5.2 
Withdrawal from Treatment .............................................................. 36 
8.6 
Premature Termination of the Study ............................................................... 37 
9 
TREATMENT OF PATIENTS ...................................................................................... 38 
9.1 
Investigational Medicinal Product ................................................................... 38 
9.1.1 
Treatment Regimens........................................................................ 38 
9.1.2 
Identity of Investigational Medicinal Product ..................................... 38 
9.1.2.1 
RV001 Vaccine 0.1 mg/mL (RV001V) .............................................. 38 
9.1.3 
Packaging and Labelling of Investigational Medicinal Product .......... 39 
9.1.4 
Storage and Handling of Investigational Medicinal Product .............. 39 
9.2 
Method of Assigning Patients to Treatment Groups ..................................... 39 
9.3 
Selection of Doses in the Study ...................................................................... 39 
9.4 
Selection and Timing of Dose for Each Patient ............................................. 40 
9.5 
Blinding............................................................................................................. 40 
9.6 
Prior and Concomitant Therapy ...................................................................... 40 
9.7 
Treatment Compliance ..................................................................................... 41 
9.8 
Drug Accountability ......................................................................................... 41 
10 
STUDY ASSESSMENTS ............................................................................................ 42 
10.1 Primary and Secondary Endpoints ................................................................. 42 
10.2 Sampling Procedures, Handling and Storage ................................................ 43 
10.3 Bioanalytical Method ....................................................................................... 43 
10.4 Demographic and Other Baseline Characteristics......................................... 43 
10.4.1 
Demographic and Baseline Data ...................................................... 43 
10.4.2 
Medical History ................................................................................ 44 
10.4.3 
Prior and Concomitant Medication ................................................... 44 
10.5 Safety Assessments ........................................................................................ 44 
10.5.1 
Safety Variables ............................................................................... 44 
10.5.2 
Adverse Events ................................................................................ 44 
10.5.3 
Physical Examination ....................................................................... 44 
10.5.4 
Vital Signs ........................................................................................ 44 
10.5.5 
Electrocardiogram ............................................................................ 44 
10.5.6 
Laboratory Safety Assessments ....................................................... 45 
10.5.7 
Other Safety Measurements ............................................................ 45 
10.6 PSA Measurements .......................................................................................... 45 
10.7 Total Blood Volumes ........................................................................................ 45 
10.8 Appropriateness of Measurements ................................................................. 46 
11 
ADVERSE EVENTS .................................................................................................... 47 
11.1 Definitions ........................................................................................................ 47 
11.1.1 
Adverse Event.................................................................................. 47 
11.1.2 
Adverse Reaction ............................................................................. 47 
11.1.3 
Unexpected Adverse Reaction ......................................................... 47 
11.1.4 
Serious Adverse Event ..................................................................... 47 
11.1.5 
Suspected Unexpected Serious Adverse Reaction .......................... 47 
11.2 Reporting of Adverse Events .......................................................................... 48 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 9 of 74 
 
11.3 Reporting of Serious Adverse Events ............................................................ 49 
11.4 Reporting of Suspected Unexpected Serious Adverse Reactions ............... 50 
11.5 Adverse Events of Special Interest ................................................................. 50 
11.6 Precautions/Overdose ..................................................................................... 51 
11.7 Pregnancy ......................................................................................................... 51 
12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ..................... 52 
12.1 Statistical and Analytical Plans ....................................................................... 52 
12.1.1 
Data Sets to be Analysed ................................................................. 52 
12.1.2 
Statistical Issues .............................................................................. 52 
12.1.3 
Summary Statistics .......................................................................... 52 
12.1.4 
Analysis of the Primary Endpoint ..................................................... 52 
12.1.5 
Analysis of Secondary Endpoints ..................................................... 54 
12.1.6 
Analysis of Exploratory Endpoints .................................................... 55 
12.1.7 
Demographic and Other Baseline Characteristics ............................ 55 
12.1.8 
Exposure to Treatment ..................................................................... 55 
12.1.9 
Concomitant Treatment .................................................................... 55 
12.2 Determination of Sample Size ......................................................................... 56 
12.3 Procedures for Reporting any Deviation(s) from the Original Statistical 
Analysis Plan .................................................................................................... 56 
12.4 Interim Analysis ............................................................................................... 56 
13 
INVESTIGATOR/SPONSOR RESPONSIBILITIES ..................................................... 57 
13.1 Ethics ................................................................................................................ 57 
13.1.1 
Independent Ethics Committee (IEC) ............................................... 57 
13.1.2 
Ethical Conduct of the Study ............................................................ 57 
13.1.3 
Patient Information and Consent (Appendix C) ................................ 57 
13.2 Patient Records and Source Data ................................................................... 57 
13.3 Access to Source Data and Documentation................................................... 58 
13.4 Monitoring ........................................................................................................ 58 
13.5 Data Management ............................................................................................ 59 
13.6 Quality Assurance and Audit .......................................................................... 59 
13.7 Record Retention ............................................................................................. 59 
13.8 Protocol Deviations.......................................................................................... 59 
13.9 Insurance .......................................................................................................... 60 
13.10 Report and Publication .................................................................................... 60 
13.11 Subject Confidentiality .................................................................................... 61 
14 
REFERENCE LIST ..................................................................................................... 62 
15 
SIGNATURES ............................................................................................................. 65 
16 
CLINICAL STUDY PROTOCOL AGREEMENT FORM............................................... 67 
17 
APPENDICES ............................................................................................................. 68 
 
LIST OF TABLES 
Table 1 
Study Flow Chart-Main Study Period .................................................................. 31 
Table 2 
Study Flow Chart-Post Treatment Long-Term Follow up of PSA and 
Immunology ....................................................................................................... 32 
Table 3 
Laboratory Safety Parameters ............................................................................ 45 
 
LIST OF FIGURES 
Figure 1 
Overall Study Design.......................................................................................... 21 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 10 of 74 
 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
3.1 
List of Abbreviations 
AE 
Adverse Event 
ADL 
Activities of Daily Living 
ADT 
Androgen Deprivation Therapy 
ALAT 
Alanine Aminotransferase 
ALP 
Alkaline Phosphatase 
AR 
Androgen Receptor 
ASAT 
Aspartate Aminotransferase 
CA 
Competent Authority 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
Cytotoxic T-lymphocyte 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic CRF 
ELISA 
Enzyme-Linked Immunosorbent Assay 
ELIspot 
Enzyme-Linked Immunospot Assay 
FU 
Follow-up  
GCP 
Good Clinical Practice 
GTPase 
Guanosine Triphosphate Hydrolase 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
ICH 
International Council for Harmonisation 
ICS 
Intracellular Staining 
IEC 
Independent Ethics Committee 
IFA 
Incomplete Freund’s Adjuvant 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IL-2 
Interleukin-2 
IMP 
Investigational Medicinal Product 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 11 of 74 
 
LDH 
Lactate Dehydrogenase 
MHC 
Major histocompatibility complex 
MMRM 
Mixed Model for Repeated Measures 
NSCLC 
Non-Small Cell Lung Cancer 
NYHA 
New York Heart Association 
OS 
Overall Survival 
PBMC 
Peripheral Blood Mononuclear Cell 
PFS 
Progression Free Survival 
PSA 
Prostate-Specific Antigen 
RhoC 
Ras Homolog Gene Family Member C 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
s.c. 
Subcutaneous 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TAA 
Tumour Associated Antigen 
TEAE 
Treatment-Emergent Adverse Event  
ULN 
Upper Limit of Normal 
 
 
3.2 
Definition of Terms 
Competent Authority 
A government body or government appointed body that has legal 
authority to approve or disapprove clinical studies 
 
 
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 12 of 74 
 
4 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
PRINCIPAL INVESTIGATORS AT  
THE PHASE I UNIT 
Name: 
Jesper Sonne 
Address:  DanTrials ApS,  
 
c/o Copenhagen University Hospital, 
 
Bispebjerg 
 
Zelo Phase I Unit, Building 11B,  
 
Bispebjerg Bakke 23, DK-2400 
 
Copenhagen NV, Denmark  
Phone: 
+45 3531 3387 
Fax:  
+45 3531 3711 
E-mail: 
jesper.sonne@regionh.dk 
INVESTIGATOR AT THE CLINIC 
Name: 
Professor Klaus Brasso 
Address: Department of Urology, 
 
Rigshospitalet 
 
Blegdamsvej 9, DK-2100 
 
Copenhagen Ø, Denmark 
Phone: 
+45 3545 7415 
E-mail: 
klaus.brasso@regionh.dk  
SPONSOR’S CLINICAL PROJECT MANAGER 
Name: 
Kerstin Danielson 
Address: RhoVac ApS 
 
SCION DTU Science Park 
 
Agern Alle 3 
 
DK 2970 Hørsholm, Denmark Phone:
 
+46 730 520 842 
E-mail: 
kd@rhovac.com  
SPONSOR’S MEDICAL EXPERT 
Name: 
Jens Kristensen 
Address: 
RhoVac ApS 
 
SCION DTU Science Park 
 
Agern Alle 3 
 
DK 2970 Hørsholm, Denmark 
Phone: 
+46 760 35 77 00 
E-mail: 
jdk@rhovac.com  
OTHER SPONSOR REPRESENTATIVES  
Name: 
Anders Ljungqvist 
Address: 
RhoVac AB,  
 
Scheelevägen 2,  
 
SE-22381 Lund, Sweden 
Phone: 
+45 40 83 23 65 
E-mail: 
alj@rhovac.com  
 
CONTRACT RESEARCH ORGANISATION 
(CRO) 
Address: TFS 
 
Scheelevägen 8,  
 
SE-223 63 Lund, Sweden 
Phone:  
+46-280 18 00 
 
 
 
BIOSTATISTICIAN 
Name:  
Mika Leinonen 
Address: Clinical Data Science GmbH 
 
Missionsstrasse 12 
 
4055 Basel, Switzerland 
Phone:  
+41 75 433 5556 
 
Email:  
mika@clindata.science  
DRUG SAFETY OFFICER 
Address: TFS 
 
Scheelevägen 8,  
 
SE-223 63 Lund, Sweden 
Phone:  
+46 28 018 00 
E-mail:  
safety.tfs@tfscro.com  

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 13 of 74 
 
CENTRAL LABORATORY  
Name: 
Bispebjerg Hospital 
Address: Bispebjerg og Frederiksberg
 
Hospital,  
 
Klinisk Biokemisk Afdeling, 
 
Bispebjerg Bakke 23, 4. Tværvej, 
 
DK-2400 Copenhagen NV, Denmark 
 
Phone: 
 +45 3531 2646 
Fax: 
+45 3531 3955 
Email:  
kba@bbh.regionh.dk  
Contact Person: 
Name:  
Ingelise Marcussen  
Phone:  
+45 2138 1020 
E-mail:  
inge-lise.marcussen@regionh.dk  
 
T-CELL MONITORING LABORATORY  
Name: 
University of Tübingen 
 
T-cell monitoring group 
Address: Auf der Morgenstelle 15 
 
72076 Tübingen 
 
Germany 
 
Contact Person: 
Name:  
Dr. Cécile Gouttefangeas 
 
Phone:  
+49 7071 29-80994  
E-mail: 
cecile.gouttefangeas@uni-
tuebingen.de  
 
PROTOCOL AUTHORS 
Name: 
Jens Kristensen 
Address: 
RhoVac ApS 
 
SCION DTU Science Park 
 
Agern Alle 3 
 
DK 2970 Hørsholm, Denmark 
Phone: 
+46 760 35 77 00 
E-mail: 
jdk@rhovac.com  
 
Name: 
Catherine Heddle  
Address: TFS 
 
Gårdsvägen 18 
 
SE-169 70 Solna, Sweden 
Phone  
+46 8 58 76 1211 
E-mail: 
catherine.heddle@tfscro.com  
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 14 of 74 
 
5 
INTRODUCTION 
5.1 
Background 
5.1.1 Cancer Vaccination Therapy  
The anticancer vaccine principle is based on the ability of the immune system to distinguish 
normal from malignant cells. This is due to cancer cells expressing so called tumour-
associated antigens (TAAs). These TAAs can be proteins or glycoproteins. They are 
expressed in connection with the malignant transformation and often caused by mutations in 
the genes of the cell leading to changes in the protein synthesis. The expression can be of 
qualitatively changed cell proteins, simple overexpression of normal proteins or de novo 
expression of proteins, which are normally only presented in small amount or not at all in the 
tissue. The antigen is broken down intracellularly and presented on the surface of the cell. 
This occurs through binding of peptide fragments to tissue type molecules (Human 
Leukocyte Antigen [HLA]) [1,2].  
Tumour-specific T lymphocytes have the ability to recognize processed tumour antigens, that 
is peptide bound to HLA on the surface of tumour cells, through their T-cell receptor. This 
interaction initiates a subsequent killing of the tumour cells. 
Therapeutic cancer vaccines work by a specific stimulation of the patient’s immune system 
with cancer antigens. Immunization with a specific tumour antigen can induce an immune 
response, which kills the tumour cells and the expression of the tumour antigen in question. 
The T-lymphocytes are the cells mainly responsible for this process. Several studies ranging 
from experimental murine systems to human clinical trials have shown that cytotoxic T-
lymphocytes (CTLs) with specificity for HLA-bound tumour peptide antigens can inhibit 
tumour growth. This is the reason why active immune therapy has been focusing on the 
activation and stimulation of tumour-specific CTL responses. 
Clinical use of peptide based vaccines has been limited due to the instability and rapid 
degradation of the peptides in their naked form. This barrier may be overcome by the 
addition of adjuvants to the peptide. Many peptide vaccine studies have been completed 
without significant toxicity, which makes peptide vaccines easy to use in a clinical context. 
The use of long peptides has led to the possibility of presentation on both major 
histocompatibility complex (MHC) class I and II and increased efficiency compared to short 
peptides [3].  
5.1.2 RhoC as a Vaccine Target 
Ras Homolog Gene Family Member C (RhoC) belongs to a family of proteins called Rho 
GTPases [4] that play a crucial role in cell migration, invasion and metastasis. The three Rho 
proteins, A, B, and C are very homogeneous, with the exception that RhoC expresses a 
unique C-terminal part. It is the unique C-terminal of RhoC that is the vaccination target, thus 
only targeting RhoC.  
RhoC seem to play a key role in cancer cell mobility, i.e., a key characteristic of metastatic 
cancer cells. Gene knock out of the RhoC gene has been shown to render melanoma cells 
incapable of metastases [5]. Thus, expression of RhoC appears to be an essential feature of 
metastatic disease.  
A RhoC biosensor has demonstrated that RhoC is active in invadopodia, which degrade 
extracellular matrix, in cancer cells. RhoC is not essential for mouse development, and 
RhoC-null mice appear phenotypically normal [6]. RhoC has been implicated in a variety of 
body functions during cancer invasion [7]. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 15 of 74 
 
Importantly, RhoC has been found to be a target for CD8 T-cells in cancer patients [8]. 
Moreover, RhoC-specific CD8 T cells harvested from patients are capable of killing cancer 
cells expressing the appropriate HLA molecule [8]. Thus, natural immune responses against 
RhoC are elicited in cancer patients, and RhoC-specific cytotoxic T-cells are detectable in 
the blood without any reported autoimmune manifestation. 
RhoC is upregulated in many types of human cancer and it contributes to cancer progression 
and metastasis formation in mouse models [5]. Thus, several lines of evidence demonstrate 
a high expression of RhoC in cancer cells, and that the metastatic potential of cancer cells 
depends on expression of RhoC [8,9,10]. RhoC has in particular been demonstrated in 
metastatic breast cancer [10], non-small cell lung cancer (NSCLC) [11], melanoma [12], 
colorectal cancer, prostate cancer [13] and carcinoid tumours [6]. 
The gene encoding RhoC has not been shown to mutate in cancers, indicating that 
upregulated expression and thus increased protein amounts in the cell, is sufficient to 
contribute to metastasis, making it a suitable target for anti-cancer vaccines to eliminate 
RhoC-expressing metastatic tumour cells. There is also evidence that it stimulates cancer 
proliferation [14,15] and resistance to chemotherapy in cultured cancer cells [16,17].  
5.1.3 RV001 
The RV001 vaccine (RV001V) targets cancer cells by eliciting an immune response against a 
RhoC-derived peptide fragment containing the C-terminal [8]. It has been demonstrated that 
RV001 can activate cytotoxic T-cells to kill RhoC-positive tumour cells in vitro [8].  
The RV001V will therefore have the potential for treatment of a variety of RhoC-expressing 
metastatic tumours. 
Preclinical toxicity studies required for use of peptide vaccines in humans have been 
performed at doses up to 225 mcg/kg, which when recalculated to human equivalent dose, is 
about 400 times the dose that will be administered to patients under this protocol. At none of 
the doses were there findings of treatment-related systemic toxicity. Local reactions at 
injection sites were noticed and so were changes compatible with immunization. These 
changes were similar in the vaccine and the adjuvant-only group of animals, indicating that 
these changes are caused by the adjuvant. 
5.1.4 Adjuvant 
Montanide ISA 51 (Seppic Inc. Paris, France) is a modified so-called incomplete Freund’s 
adjuvant (IFA). Montanide ISA 51 is defined as a mixture of a highly purified mineral oil 
(Drakeol 6VR) and a surfactant (Mannide monooleate) [18]. When mixed with an aqueous 
phase in a 50/50 ratio, it renders a water in oil emulsion. This water in oil emulsion is used as 
vaccine adjuvant, in order to enhance the immune response against antigens. IFA is used 
with success in combination with long peptides, where clinically relevant responses can be 
produced with IFA. For instance, in a vaccine with a long HPV-16 peptide against vulva 
cancer [19,20,21].  
5.2 
Study Rationale 
This is an open-label first-in-human study for the peptide cancer vaccine RV001V 
administered to prostate cancer patients who previously have been treated with total 
prostatectomy. The primary objective is to assess tolerability and safety of subcutaneous 
administration of RV001V, comprising a synthetic peptide derived from RhoC and the 
adjuvant Montanide ISA 51. The secondary objective is to asses if the vaccination can 
induce a measurable vaccination-specific T-cell response in prostate cancer patients. 
Prostate-specific antigen (PSA) is monitored for exploratory purposes. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 16 of 74 
 
Prostate cancer 
Prostate cancer is the most common cancer in the Danish male population with 4316 
patients diagnosed in 2012. During the last 10 years incidence has nearly doubled, mostly 
due to increased unsystematic screening, whereas the mortality rate has been more or less 
unchanged at about 1100 deaths annually [22]. 20-30% of patients diagnosed with localized 
disease will develop metastatic disease and another 15% of men diagnosed with prostate 
cancer will present with metastatic disease at the time of diagnosis [23].  
Standard treatment of prostate cancer  
When limited to the prostate only, prostate cancer can potentially be cured through 
prostatectomy or radiotherapy. If the cancer has spread, usually in the form of bone- and/or 
lymph metastasis, treatment options are limited to life prolonging and palliative therapies. 
Androgen deprivation therapy (ADT) serves as a backbone for such treatment, including 
medical or surgical castration and treatment with androgen receptor (AR) targeting therapies 
(e.g. bicalutamide) [24]. In patients with “high-volume disease” chemotherapy (early 
docetaxel) can be added to ADT as this combination has demonstrated a survival benefit 
compared to ADT alone in recent studies [25]. In addition to improving disease related 
symptoms, ADT leads to a decline in PSA levels in about 80% of treated patients. Despite 
such a high initial response rate, the cancer will however progress within 1-2 years [26]. At 
this point the disease is termed metastatic castration-resistant prostate cancer, a disease 
stage harbouring a poor prognosis with a median overall survival (OS) of around 2-3 years 
[26]. Even though the disease is now termed castration-resistant, androgen synthesis and 
the AR are still targets for further anti-cancer therapy involving abiraterone (an androgen 
synthesis inhibitor) and enzalutamide (a novel AR antagonist) [27,28]. If response to ADT 
has been short lived however, chemotherapy with docetaxel is usually preferred before 
treatment with these agents (abiraterone or enzalutamide) [29,30,31]. In the case of patients 
who have a good performance status additional chemotherapy can be added (cabazitaxel 
[32]). For selected patients with symptomatic bone metastases treatment with radium-223 is 
also an option [33]. 
5.3 
Potential Risks and Benefits 
The RhoC peptide RV001V vaccine is tested as a ”first in man” in this study and therefore 
the primary objective is to assess safety and tolerability. Peptide vaccines have been tested 
since 1995 [34] and are generally without pharmacological activity despite induction of a 
biological response against the vaccination target and despite expression of the target 
protein in various healthy tissues. Since the biological target – the RhoC protein - is 
expressed in normal cells in various tissues, these cells and tissues could potentially lead to 
adverse effects of the vaccination. However, RhoC is supposedly expressed by much lower 
levels in non-cancerous tissues thus not at levels sufficient for recognition by RhoC specific 
T-cells. 
In contrast to other cytotoxic therapies, cancer vaccines have demonstrated minimal toxicity 
in all clinical trials that have been reported to date [35,36]. Despite expression of many target 
Tumour-associated antigens in normal tissues, little evidence of autoimmunity has been 
observed, with the exception of vitiligo that is seen in patients receiving some melanoma 
vaccines [37,38]. As with all vaccines, there is a theoretical risk of unspecific autoimmune 
reactions. There can also be a risk of allergic reactions when administering this type of drug. 
Blood draws and insertion of indwelling catheters may be associated with discomfort at the 
puncture site with bruising, bleeding, infection, and, rarely, fainting and local nerve damage. 
Some people tolerate badly the adhesive and / or gel used for attaching electrocardiogram 
(ECG) electrodes and some skin irritation can occur. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 17 of 74 
 
The adjuvant Montanide ISA 51 has been tested in AIDS and cancer vaccines in thousands 
of patients [18]. The most common local adverse reactions are formation of granulomas, 
localized pain, inflammation, and erythema at the injection site. In addition, systemic side 
effects such as fever, headache, fatigue and GI disorders have been reported. These 
reactions are usually classified as mild or moderate and as being transient. It has been 
shown that the purified mineral oil emulsion that the Montanide ISA 51 adjuvant consists of is 
quickly eliminated by macrophages. Systemic adverse reactions consist of headache, chills, 
fewer and GI disorders and are often mild to moderate. On rare occasions when severe 
systemic adverse reactions occur, they are often related to the dosage of Montanide ISA 51.  
This study will potentially add to existing knowledge in the field of immune therapy and help 
to improve the development of treatments and thus prognosis in these types of cancers. This 
study can contribute with descriptions of alterations in cancer specific immune reactivity 
associated with the given treatment, of benefit for further understanding of the immune 
system role in cancer treatment. The scientific background for the use of RV001V in cancer 
is built on the hypothesis that potential metastasis can be eliminated. There might therefore 
be a theoretical benefit for patients with metastatic disease, although there is no evidence of 
such potential effect. 
The benefits for the society and the potential benefits for the individual patient are expected 
to outweigh the risks and it is therefore deemed appropriate to perform the study. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 18 of 74 
 
6 
STUDY OBJECTIVES 
6.1 
Primary Objective 
The primary objective is to evaluate the safety and tolerability of RV001 Vaccine 0.1 mg/mL 
(RV001V) following subcutaneous (s.c.) administrations to patients who have been 
prostatectomised due to prostate cancer. 
6.2 
Secondary Objectives 
The secondary objective is to investigate RV001V-specific T-cells in treated patients, and 
thereby the immunological response before, during and after vaccination. 
6.3 
Exploratory Objectives 
The exploratory objectives are to investigate the PSA levels both in the subgroup of patients 
with measurable levels at baseline and in patients with no measurable levels at baseline, to 
explore the potential associations between PSA levels and immunological response and to 
preliminarily evaluate the progression-free survival (PFS) and OS. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 19 of 74 
 
7 
INVESTIGATIONAL PLAN 
7.1 
Study Design and Plan Description 
The trial is an open phase I/II first-in-human clinical study for a peptide cancer vaccine. 
Between 10 and 25 patients prostatectomised due to prostate cancer will be enrolled.  
The treatment will consist of a total of 11 s.c. vaccinations with RV001V. The first 
6 vaccinations will be given every 2 weeks, whereas the remaining 5 vaccinations will be 
administered with 4 weeks between each vaccination. Long term follow-up of immunological 
response and PSA levels will be performed at 3, 6, 9 and 12 months after the last 
vaccination.  
The first three patients will be enrolled sequentially. Patient no 1 will have 2 vaccinations 
before any additional patient can be treated. Provided that no safety concern is observed 
after safety evaluation of the two first vaccinations, Patient no 2 may start vaccination and a 
new safety readout will be performed when patient no 2 has received 2 vaccinations. 
Provided no safety concern is observed from the two first patients, Patient no 3 may start 
vaccination. A new safety readout will be performed when all 3 patients have received at 
least 2 vaccinations and provided no safety concern is observed, three additional patients may 
start vaccinations with their first vaccination taking place on separate days. Following a new safety 
readout, and provided no safety concern is observed, all remaining patients may start vaccinations 
with their first vaccination taking place on separate days. All vaccinations will be performed at Zelo 
Phase I Unit. 
There will in total be 17 visits; Visit 1a and 1b screening, followed by Visit 2-12 vaccinations, 
Visit 13 follow-up visit post dosing and long term post dose follow-up visits, Visit 14-17. Visit 
1a will be done at the Department of Urology, Rigshospitalet. Remaining visits, visits 1b-17 
will be done at Zelo Phase I Unit. 
At each vaccination visit, patients will undergo safety assessments and provide blood 
samples for assessment of haematology, clinical chemistry and PSA. Before the 1st, the 5th, 
the 7th vaccination and 4 weeks after the 11th vaccination blood will be drawn for lymphocytic 
evaluation. 
At the long-term follow up visits, Visit 14-17, blood will be drawn for lymphocytic evaluation 
and measurement of PSA. 
Outside the scope of this study, the patients will be followed and treated by the investigators 
at the hospital on a regular basis according to the hospital clinical practice. The PSA analysis 
performed at the Phase I unit will be reviewed by the investigator at the hospital. For each 
PSA value, the investigator at the hospital will, based on their standard clinical assessment, 
issue a statement regarding the patient’s clinical cancer status (Stable or progression). 
The trial will be terminated if treatment related grade 3, 4 or 5 toxicity in accordance with 
Common Terminology Criteria for Adverse Events (CTCAE) is observed in more than one of 
the first 6 patients, with the exception of fever. 
While the study is ongoing, the intensive care unit (ICU) at Bispebjerg Hospital will be 
informed of the vaccination schedule, as intensive care support could potentially be required 
if a treated patient develops anaphylactic shock.  
In case the patient develops disease progression, requiring surgical and/or chemotherapeutic 
treatment, the patient will be discontinued from the study and referred back to the 
Department of Urology, Rigshospitalet, from which he was referred initially, where treatment 
will be offered independent of participation in the study. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 20 of 74 
 
7.1.1 
Interim Safety Evaluation 
Interim safety evaluation will be conducted after each of the 3 first patients has received their 
2nd vaccination.  
At each assessment, the treating Investigator will make a safety evaluation of all treated 
patients, document and make it available to a safety review committee. The safety evaluation 
data to be reviewed will consist of: 
• 
AEs 
• 
Vital signs 
• 
Physical examination 
• 
ECG 
• 
Laboratory data covering 2 weeks after the 1st vaccination 
The safety review committee will, in accordance with pre-defined criteria and stopping rules, 
evaluate safety prior to enrolment of the next patient. Further details are given in the Safety 
Review Charter, This procedure will be repeated for the second and third patient treated, see 
Figure 1. 
The safety review committee will comprise a minimum of, but is not limited to: 
• 
Principal investigator at Zelo Phase I Unit. 
• 
Co-Investigator from the Department of Urology, Rigshospitalet. 
• 
Sponsor’s medical responsible 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 21 of 74 
 
 
Figure 1 
Overall Study Design 
Initial patient enrolment and treatment – Vaccination overview 
 
Visit
Sceening 1a and 1b
2
3
4
5
6
7
8
9
10
11
12
13
Days
1
15
29
43
57
71
Patient 1, dose no.
1st
2
3
4
5
6
7
8
9
10
11
FU
Days
≥16
≥30
≥44
Patient 2, dose no.
1st
2
3
4
5
6
7
8
9
10
11
FU
Days
≥31
≥45
Patient 3, dose no.
1st
2
3
4
5
6
7
8
9
10
11
FU
Remaining patients
≥46
1st
2
3
4
5
6
7
8
9
10
11
FU
1st
2
3
4
5
6
7
8
9
10
11
FU
Recruit between 7 and 22 
patients
-30 to -1
221
251
101
131
161
191

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Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
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Confidential 
Page 22 of 74 
 
 
7.2 
Study Procedures 
7.2.1 Schedule of Study Events 
The study assessments described in the sections below are presented in detail in Section 
10.1 (primary and secondary endpoints), Section 10.4 (demographic data and baseline 
characteristics) and Section 10.5 (safety assessments). Recording and reporting of AEs are 
described in detail in Section 11. 
The timing of all study events is shown in Table 1 and Table 2 in 7.2.2.  
7.2.1.1 
Visit 1a and Visit 1b (Screening Visit, Day -30 to -1) at Rigshospitalet and 
Zelo Phase I Unit 
Visit 1a performed at the Department of Urology at Rigshospitalet 
Pre-screening of patient and obtaining informed consent. No study assessments may be 
performed before informed consent has been obtained. 
• 
Informed consent  
• 
Initial assessment of eligibility based on medical history, concomitant medication and 
available laboratory data 
• 
Medical history 
• 
Prior and concomitant medication 
• 
Performance status according to the Eastern Cooperative Oncology Group (ECOG) 
scale 
• 
Determination of clinical cancer status (stable disease or progression) 
Visit 1b performed at Zelo Phase I Unit 
No study assessments may be performed before informed consent has been obtained. The 
following assessments must be performed within a month prior to the start of vaccinations. 
Blood tests must be performed within one week prior to start of vaccinations: 
• 
Confirmation that informed consent has been obtained 
• 
Confirmation of eligibility  
• 
Physical examination 
• 
Demographic information (date of birth, sex, ethnicity) 
• 
Vital signs: blood pressure, pulse rate and temperature 
• 
Body measurements: body weight, height 
• 
Medical history 
• 
Prior and concomitant medication 
• 
Performance status according to the ECOG scale 
• 
Blood tests 
o Haemoglobin, red blood cell (RBC) count, haematocrit, leukocytes, differential 
counts and platelets  

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o Sodium, creatinine, albumin, lactate dehydrogenase (LDH), alkaline 
phosphatase (ALP), aspartate aminotransferase (ASAT), alanine 
aminotransferase (ALAT), total bilirubin, potassium, calcium, C-reactive 
protein (CRP), blood glucose, HbA1c 
o Hepatitis B core antibody, hepatitis B surface antigen, hepatitis C virus, 
human immunodeficiency virus (HIV) 
o PSA 
• 
Urine dipstick: Glucose, bilirubin, ketones, specific gravity, blood, pH, protein, 
urobilinogen, nitrite, leucocytes 
• 
12-lead ECG 
Visit 1a and 1b may take place on the same day. 
 
7.2.1.2 
Visit 2 (Day 1), at Zelo Phase I Unit 
At Visit 2, the following activities and assessments will be performed:  
• 
Confirmation of eligibility 
• 
Physical examination 
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Blood tests (safety) 
• 
12-lead ECG before, 60 and 120 minutes after vaccination 
• 
Blood sampling for HLA tissue type determination 
• 
Blood sampling for Lymphocyte evaluation 
• 
Vaccination no 1 
• 
Heart rate and blood pressure 30, 60 and 120 min after vaccination 
• 
Adverse events (Common Toxicity Criteria [CTC]), after first Vaccination 
• 
Injection site reactions 
• 
Observation in phase I unit for at least 2 hours after vaccination 
 
7.2.1.3 
Visit 3 (Day 15±2) at Zelo Phase I Unit 
At Visit 3, the following activities and assessments will be performed:  
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 

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• 
12-lead ECG before 60 and 120 minutes after vaccination 
• 
Vaccination no 2 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30, 60 and 120 min after vaccination 
• 
Observation in phase I unit for at least 2 hours after vaccination 
 
7.2.1.4 
Visit 4 (Day 29±2), at Zelo Phase I Unit 
At Visit 4, the following activities and assessments will be performed:  
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 
• 
PSA 
• 
12-lead ECG before, 60 and 120 minutes after vaccination 
• 
Vaccination no 3 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30, 60 and 120 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in phase I unit for at least 2 hours after vaccination 
 
7.2.1.5 
Visit 5 (Day 43±5), at Zelo Phase I Unit 
At Visit 5, the following activities and assessments will be performed: 
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Vaccination no 4 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Observation in clinic for at least 1 hour after vaccination 
 

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7.2.1.6 
Visit 6 (Day 57±5), at Zelo Phase I Unit 
At Visit 6, the following activities and assessments will be performed: 
• 
Vital Signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
Vaccination no 5 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.7 
Visit 7 (Day 71±5), at Zelo Phase I Unit 
At Visit 7, the following activities and assessments will be performed:  
• 
Physical examination 
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
PSA 
• 
Vaccination no 6 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.8 
Visit 8 (Day 101±7), at Zelo Phase I Unit 
At Visit 8, the following activities and assessments will be performed:  
• 
Vital signs before vaccination 
• 
Changes in concomitant medication 

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• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
12-lead ECG before and 60 minutes after vaccination 
• 
Vaccination no 7 
• 
Injection site reactions 
• 
Heart rate, blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.9 
Visit 9 (Day 131±7), at Zelo Phase I Unit 
At Visit 9, the following activities and assessments will be performed:  
• 
Vital Signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
PSA 
• 
Vaccination no 8 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.10 
Visit 10 (Day161±7), at Zelo Phase I Unit 
At Visit 10, the following activities and assessments will be performed:  
• 
Vital Signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 
• 
PSA 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 27 of 74 
 
• 
Vaccination no 9 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.11 
Visit 11 (Day 191±7), at Zelo Phase I Unit 
At Visit 11, the following activities and assessments will be performed:  
• 
Vital Signs before vaccination 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
PSA 
• 
Vaccination no 10 
• 
Injection site reactions 
• 
Heart rate and blood pressure 30 and 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.12 
Visit 12 (Day 221±7), at Zelo Phase I Unit 
At Visit 12 the following activities and assessments will be performed:  
• 
Physical examination 
• 
Vital signs 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
PSA 
• 
Vaccination no 11 
• 
Injection site reactions 
• 
Heart rate, blood pressure 30 and 60 min after vaccination  
• 
12-lead ECG 60 min after vaccination 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 28 of 74 
 
• 
Observation in clinic for at least 1 hour after vaccination 
 
7.2.1.13 
Visit 13 (Day 251±14), End of Treatment Follow Up (30 days After Last 
Vaccination), at Zelo Phase I Unit 
This end of treatment follow-up will take place in all patients, also those that withdraw 
prematurely. 
At Visit 13, the following activities and assessments will be performed:  
• 
Physical examination 
• 
Vital signs 
• 
Changes in concomitant medication 
• 
Weight 
• 
Adverse events (CTC) 
• 
Blood tests (safety) 
• 
Urine dipstick: glucose, bilirubin, ketones, specific gravity, blood, pH, protein, 
urobilinogen, nitrite, leucocytes 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
12-lead ECG 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
 
7.2.1.14 
Visit 14 (3 months) Long Term Follow Up Post Last Dose, at Zelo Phase I 
Unit 
At Visit 14, the following activities and assessments will be performed:  
• 
Weight 
• 
Adverse events (CTC). Recording of study/protocol related AEs and serious adverse 
events (SAEs) suspected to be related to study treatment or procedures 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
If patients fail to return for these assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, letter) should be made by the Investigator to contact them. 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 29 of 74 
 
7.2.1.15 
Visit 15 (6 months), Long Term Follow Up Post Last Dose, at Zelo Phase I 
Unit 
At Visit 15, the following activities and assessments will be performed:  
• 
Weight 
• 
Adverse events (CTC). Recording of study/protocol related AEs and SAEs suspected 
to be related to study treatment or procedures 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
If patients fail to return for these assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, letter) should be made by the Investigator to contact them. 
 
7.2.1.16 
Visit 16 (9 months), Long Term Follow Up Post Last Dose, at Zelo Phase I 
Unit 
At Visit 16, the following activities and assessments will be performed:  
• 
Weight 
• 
Adverse events (CTC). Recording of study/protocol related AEs and SAEs suspected 
to be related to study treatment or procedures 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 
• 
If patients fail to return for these assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, letter) should be made by the Investigator to contact them. 
 
7.2.1.17 
Visit 17 (12 months) Long Term Follow Up Post Last Dose, at Zelo Phase 
I Unit 
At Visit 17, the following activities and assessments will be performed: 
• 
Weight 
• 
Adverse events (CTC). Recording of study/protocol related AEs and SAEs suspected 
to be related to study treatment or procedures 
• 
PSA 
• 
Sampling for Lymphocyte evaluation 
• 
Request determination of clinical cancer status (stable disease or progression) from 
Department of Urology at Rigshospitalet 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 30 of 74 
 
• 
If patients fail to return for these assessments for unknown reasons, every effort (e.g. 
telephone, e-mail, letter) should be made by the Investigator to contact them. 
 
7.2.2 Study Flow Chart 
The study flow chart for the main study period is shown in Table 1 and for the follow up 
period in Table 2. 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 31 of 74 
 
Table 1 
Study Flow Chart-Main Study Period 
Procedures will be performed at the Zelo Phase I Unit only unless otherwise indicated. 
Visit  
1a+1b 
 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13  
(EOT  
Follow 
up) 
Day 
 
Screen 
Day  
-30 to -1 
1  
15 
(±2 
days) 
29 
(±2 
days) 
43 
(±5 
days) 
57  
(±5 
days) 
71  
(±5 
days) 
101  
(±7 
days) 
131 
(±7 
days) 
161  
(±7 
days) 
191 
(±7 
days) 
221  
(±7 
days) 
251 
(±14 
days) 
Vaccination no 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
FU 
Informed consent  
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
Xb 
Xc 
 
 
 
 
 
 
 
 
 
 
 
Demographic information 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
Determination of cancer status (stable 
or progression) 
Xa 
 
 
Xa 
 
Xa 
Xa 
Xa 
Xa 
Xa 
Xa 
Xa 
Xa 
Vital signs (pulse rate, blood 
pressure, body temperature) 
X 
Xd 
Xd 
Xd 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
X 
Medical History 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant medication  
Xb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Performance status (ECOG) 
Xb 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events (CTC) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Injection site reactions 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood testsf 
Xg 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
X 
Urinalysis (dipstick) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
HIV, HBV and HCV tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Lymphocyte evaluationh 
 
X 
 
 
 
X 
 
X 
 
 
 
 
X 
ECG 
X 
Xi 
Xi 
Xi 
 
 
 
Xi 
 
 
 
Xj 
X 
PSA 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
HLA tissue type determination 
 
X 
 
 
 
 
 
 
 
 
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 32 of 74 
 
EOT= End of treatment, FU= Follow-up, HBV= Hepatitis B virus, HCV= Hepatitis C virus 
a Will be performed at Department of Urology at Rigshospitalet only.  
b Will be performed both at Department of Urology at Rigshospitalet and at Zelo Phase I Unit. 
c Re-check of eligibility criteria before first vaccination. Results from haematology and clinical chemistry at screening will determine eligibility. 
d During administration of the first 3 vaccinations, the patient is observed for at least 2 hours after vaccination with measurements of pulse and blood pressure before and after 
the vaccine is given 
e During administration of vaccination 4 to 11 the patient is observed for at least 1 hour after vaccination with measurements of pulse and blood pressure before and after the 
vaccine is given 
f Blood tests = Haemoglobin, RBCs, haematocrit, leukocytes and differential counts, platelets, CRP, LDH, creatinine, sodium, potassium, calcium, albumin, ASAT, ALAT, total 
bilirubin, alkaline phosphatase. Blood glucose and HbA1c only at screening. 
g Blood tests are to be performed within 1 week of vaccination start. 
h See “Blood Tests for Lymphocyte Evaluation” in Section 10.2 
i During administration of the first 3 vaccinations and vaccination number 7, ECG measurements before and after the vaccine is given 
j At administration of vaccine 11, ECG measurement 60 minutes after vaccination 
 
Table 2 
Study Flow Chart-Post Treatment Long-Term Follow up of PSA and Immunology 
Visit 
14 
15 
16 
17 
 
Months following last vaccination 
3 
6 
9 
12 
Weight 
X 
X 
X 
X 
PSA 
X 
X 
X 
X 
Lymphocyte evaluationa 
X 
X 
X 
X 
Determination of cancer status (stable disease or progression) 
X 
X 
X 
X 
Recording of study/protocol related AEs and SAEs suspected to be related to study 
treatment or procedures 
X 
X 
X 
X 
a See “Blood Tests for Lymphocyte Evaluation” in Section 10.2

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 33 of 74 
 
7.3 
Discussion of Study Design, Including the Choice of Control Groups 
It is anticipated that 10 patients will be sufficient for evaluation of the primary endpoint. 
The primary and secondary objectives of the study can be answered in PT patients 
independent of their PSA status. However, as an exploratory aim, we will evaluate PSA 
kinetics during the treatment and potential association to immune response to vaccination. 
For this reason we aim to include patients with measurable and rising PSA levels, although, 
should this be difficult or result in more dropouts than anticipated, PT patients without 
measurable PSA will also be included to secure the primary and secondary endpoint.  
Due to the exploratory nature of this open study no placebo group is included. 
The 1 year long term follow up period is aimed to explore the duration of the immune 
response. 
The adjuvant used in this study is Montanide ISA 51 which is a so called in-complete 
Freund’s adjuvant developed specifically for use as an adjuvant in therapeutic cancer 
vaccines. The dose (volume) of the adjuvant Montanide ISA 51 is reported to have been 
used in volumes from 0.1 mL to as high as 5.0 mL. From previous experience a dose of 
approx. 0.5 mL of Montanide ISA 51 has shown to provide the required enhancement of 
antigen-specific immune responses [39]. Hence, this target volume was also chosen for this 
trial. 
7.4 
Study Period 
The duration of the study is expected to be approximately 2 years, beginning with first patient 
first visit which is anticipated to occur in Q1 2017, and ending with last patient last follow up 
visit in Q1 2019. All patients are expected to be enrolled and have completed vaccine 
treatment during the first year. The second year will consist of follow up visits. The actual 
overall study duration will depend on the time required to screen and enrol patients, the 
number of patients needed, and whether patients complete all treatment and follow up visits. 
7.5 
End of Study 
The end of study is defined as the date of the last patient’s last visit.  
The end of the treatment phase of the study will be when the last patient has completed Visit 
13/end of treatment follow-up visit. 
The end of the long-term follow-up phase of the study will be when the last patient has 
completed the last follow-up visit.  

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 34 of 74 
 
8 
SELECTION OF STUDY POPULATION 
8.1 
Number of Patients 
At least 10 patients will be enrolled in the trial to fulfil the primary objective. Additional 
patients, up to a total of 25 patients, may be enrolled dependent on analysis of immune 
related data. With an estimated dropout rate of 25% up to 20 patients may complete all 
vaccinations. 
8.1.1 Recruitment  
Patients will be recruited from the Department of Urology at Rigshospitalet. Patients will be 
identified from the hospitals database of patients who have undergone radical prostatectomy. 
Approximately, 300 patients are prostatectomised due to prostate cancer each year at 
Rigshospitalet and therefore it is estimated that patient inclusion can be completed within 4 
months. 
 
8.2 
Inclusion Criteria 
The patients have to meet all of the following criteria to be eligible to enter the study: 
1) Patients prostatectomised (PT) due to histologically verified adenocarcinoma of the 
prostate gland who currently are not being treated, or expected within the next 8 months 
to be treated, with any anti-cancer treatment. Patient may or may not have measurable 
PSA. 
2) Able to understand the study procedures and willing to provide informed consent 
3) Able and willing to comply with study requirements and complete all visits  
4) Using adequate contraceptive measures 
All non-vasectomized patients must use condoms during the study and for one month 
after the last vaccination with RV001V, or have a female partner who either has been 
post-menopausal for more than one year or is using a highly effective method of 
contraception (i.e. a method with less than 1% failure rate). 
5) Aged 18 years and above. 
6) ECOG performance status 0 or 1 (Appendix A). 
7) Recovered/stabilized at grade ≤2 from all toxicities related to prior treatment(s) in 
accordance with CTCAE. 
8) Laboratory values obtained ≤30 days prior to first dose, and more than 3 weeks after 
potential chemotherapy 
a. Haemoglobin ≥5.6 mmol/L 
b. Absolute granulocyte count ≥1.5 x 109 /L 
c. Platelets ≥100 x 109 /L 
d. Total bilirubin ≤1.5 x upper limit of normal (ULN) 
e. Creatinine ≤1.5 x ULN 
f. ALAT, ASAT and ALP ≤2.5 x ULN. 

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8.3 
Exclusion Criteria 
Patients meeting any of the following criteria will not be permitted to enter the study: 
1) Patient is a candidate for relevant therapies that are the current standard of care for their 
cancer disease. 
2) Patient has been treated with Androgen Deprivation Therapy (ADT), or expected to 
receive such treatment within the next 8 months from enrolment. 
3) Concurrent chemotherapy or radiotherapy within 12 weeks of 1st vaccination, or expected 
to receive such treatment within the next 8 months from enrolment. 
4) Patients have undergone major surgery or have had major bleeding within the last month 
prior to the first vaccination. 
5) Patients with brain or leptomeningeal metastases. 
6) Prior treatment with any therapeutic cancer vaccine(s). 
7) History of second malignancy (except for adequately managed basal cell carcinoma and 
squamous cell carcinoma of the skin). 
8) Patients in need of or treated the last 30 days before the first vaccination with systemic 
steroids or other immune suppressive therapy. Use of inhaled steroids, nasal sprays, and 
topical creams for small body areas is allowed. 
9) History of alcohol or substance abuse within the last 5 years  
10) History of acquired immune deficiency syndrome or positive serological test for HIV 
infection 
11) History of viral hepatitis B as determined by positive antibody immunoglobulin M (IgM) to 
core antigen for hepatitis B or positive for hepatitis B surface antigen, or viral hepatitis C 
as determined by positive antibody for hepatitis C  
12) Participation in any investigational trial or use of any investigational drug(s) within 
30 days prior to inclusion in this trial. 
13) Any known serious infections, e.g. tuberculosis. 
14) History of significant autoimmune disease such as: Inflammatory bowel disease, 
Systemic lupus erythematosus, Ankylosing spondylitis, Scleroderma, Multiple sclerosis 
15) Severe medical conditions, such as but not limited to severe asthma/ Chronic obstructive 
pulmonary disease (COPD), New York Heart Association (NYHA) grading 3 or above, 
poorly regulated insulin-dependent diabetes, any significant organ damage as judged by 
the Investigator. 
16) Other medications or conditions that in the Investigator's opinion would contraindicate 
study participation for safety reasons or interfere with the interpretation of study results 
17) History of multiple drug allergies or known allergy/hypersensitivity to Montanide ISA 51, 
or intolerance to subcutaneous injection. 
8.4 
Restrictions  
The following restrictions apply during vaccine treatment:  
Vaccination within 1 week of a major viral infection, bacterial infection requiring systemic 
antibiotics, or administration of other vaccinations. In such situations, it is allowed to 
postpone RV001V vaccinations up to 3 weeks, see Section 8.5. 

Clinical Study Protocol 
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Study Code: RhoVac-001 
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8.5 
Removal of Patients from Therapy or Assessment 
8.5.1 Withdrawal from Study 
Patients are free to discontinue their participation in the study at any time. Withdrawal from 
the study will not affect or prejudice the patient’s further care or treatment. Patients may be 
withdrawn from study treatment and assessments at any time, if deemed necessary by the 
Investigator. 
Potential reasons for withdrawal of patients from this study are:  
• 
Screening failure 
• 
The decision of a patient to withdraw from the study (including if the patient withdraws 
informed consent). The treatment can be stopped at any time the patient wishes to do 
so. 
• 
Unacceptable toxicity. Treatment is terminated if AEs occur that are of a degree that 
makes completion of the study impossible. That is treatment related grade 3, 4 or 5 
toxicity in accordance with CTCAE (except fever). 
• 
Medical decision. The Investigators can stop treatment at any time if he/she feels it is 
in the patients’ best interest, e.g. due to medical conditions. 
• 
Administration of concomitant medication prohibited by this protocol. 
• 
Need of alternative treatment. Patients will be excluded at any time a new treatment 
with an experimental drug or other systemic anticancer treatment is initiated after 
inclusion in this protocol. If Androgen Deprivation Therapy (ADT) is initiated, the 
patient may continue treatment and follow up when agreed between the investigator 
at the hospital and the sponsor’s medical experts. The patient will be excluded if 
systemic treatment with corticosteroids is initiated unless it is agreed with the sponsor 
medical expert that the patient can continue in the study.  
• 
Delayed treatment. The patient will be withdrawn from the study if a scheduled 
vaccination is delayed more than 3 weeks. It is the responsibility of the investigator to 
assess the cause of delay and define the time point for the start of the delay. A 
patient can be delayed several times during the cause of treatment without being 
excluded. I case a vaccination has to be delayed, the clock will be put on hold until 
the vaccination can be performed and the patients continued study related activities 
will be rescheduled. 
• 
Patient is lost to follow-up 
The reason and date the patient is withdrawn from the study will be documented in the case 
report form (CRF) (e.g. lost to follow-up, consent withdrawn, incorrect enrolment, AEs, etc.).  
If a patient is withdrawn from the study, all safety data collected until the time of withdrawal 
will be used in the analyses, and efficacy data will be used if 3 or more vaccinations have 
been administered.  
Patients, who are excluded from the study, will be referred back to the urology/oncology 
team, from which they were recruited, for standard treatment. Patients that are excluded 
before the 3rd vaccination will be replaced with a new patient. 
 
8.5.2 Withdrawal from Treatment 
If a patient is withdrawn from further treatment with the investigational medicinal product 
(IMP), the End of Treatment visit (Visit 13) should be completed. 

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Patients who discontinue treatment with the IMP and who received 3 or more vaccinations, 
should continue with the long-term follow-up visits(visits 14-17). If a patient fails to return for 
these assessments for unknown reasons, every effort (e.g. telephone, e-mail, letter) should 
be made by the Investigator to contact them. 
8.6 
Premature Termination of the Study 
The Investigator or the Sponsor may terminate this study prematurely for any reasonable 
cause. The Independent Ethics Committee (IEC) and Competent Authority (CA) will be 
informed promptly.  
Conditions that may warrant termination include, but are not limited to: 
• 
The discovery of an unexpected, significant, or unacceptable risk to the patients 
enrolled in the study, or potential study patients 
• 
A decision on the part of the Sponsor to suspend or discontinue development of the 
IMP 
If the CA obtains information that raises doubts about the safety or scientific validity of the 
clinical study, the CA can suspend or prohibit the study. Before the CA reaches its decision, 
it shall, except where there is imminent risk, ask the Sponsor and/or the Investigator for their 
opinion, to be delivered within one week (Directive 2001/20/EC, Article 12, Section 1).  
If the study is prematurely terminated or suspended for any reason, the Investigator should 
promptly inform the study patients and should assure appropriate therapy and follow-up for 
the patients.  

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 38 of 74 
 
9 
TREATMENT OF PATIENTS 
9.1 
Investigational Medicinal Product 
9.1.1 Treatment Regimens 
The vaccine will be administered as a subcutaneous injection of 1 ml on the upper arm 
alternating between the right and left side. Dosage per vaccine injection will be 100 µg of 
RV001 peptide dissolved in in an aqueous buffer and homogenized immediately before 
administration with Montanide ISA 51 (adjuvant) in a 50:50 ratio. 
The vaccine is injected into the subcutaneous tissue of the upper arm after disinfection of the 
skin. During administration of the first 3 vaccinations (Visits 2, 3 and 4), the patient is 
observed for at least 2 hours with measurements of pulse and blood pressure before 
vaccination, 30, 60 and 120 min after the vaccine is given. Patients are observed for acute 
toxicities in the form of allergic reactions, including anaphylactic shock. Allergic reactions 
and/or anaphylactic shock will be treated according to hospital guidelines. For the remaining 
vaccinations, the patient will be observed for at least 1 hour following each injection and with 
measurement of blood pressure and pulse rate before and 30 and 60 min after vaccination. 
The intensive care unit at Bispebjerg Hospital will be informed of the vaccination schedule, 
as intensive care support could potentially be required if a treated patient develops 
anaphylactic shock. 
9.1.2 Identity of Investigational Medicinal Product 
9.1.2.1 
 RV001 Vaccine 0.1 mg/mL (RV001V) 
The active constituent in RV001 Vaccine 0.1 mg/mL is the synthetic peptide RV001, which 
has the same amino acid sequence as the C-terminal of the RhoC protein: 
Ala-Thr-Arg-Ala-Gly-Leu-Gln-Val-Arg-Lys-Asn-Lys-Arg-Arg-Arg-Gly-Cys-Pro-Ile-Leu 
The RV001 Vaccine 0.1 mg/mL (RV001V) is an emulsion where the aqueous phase is a 
solution of the RV001 peptide and the oil phase is the adjuvant (Montanide ISA 51). 
The aqueous phase of the emulsion is named RV001 Injection 0.2 mg/mL, and is a sterile 
clear, colourless solution. It is formulated using the peptide RV001 as the active ingredient, 
sodium acetate and acetic acid as buffer and sodium chloride as a tonicity agent. The pH of 
the solution is approximately 3.5. The solution is filled at a nominal volume of 1 mL into 
single-use clear glass vials which is stoppered and capped. 
The composition of RV001 Injection 0.2 mg/mL (the aqueous phase) is tabulated below: 
 
Component 
Content 
Function 
RV001 (100%, anhydrous) 
0.200 mg Active Ingredient 
Sodium acetate trihydrate  
0.180 mg Buffer 
Acetic acid glacial 
0.142 mg Buffer 
Sodium chloride 
0.292 mg Tonicity 
Water for Injection 
qs to make 1 mL  Solvent 
 
Immediately before administration to the patient (within 15 min), 1 mL of RV001 Injection 
0.2 mg/mL is mixed and emulsified with 1 mL of Montanide ISA 51 using two syringes and an 
I-connector as described in “Instruction for Use”. The resulting emulsion (RV001V) is a 
water-in-oil emulsion and 1 mL of this emulsion is administered to the patient. The amount 
administered will contain 0.1 mg RV001. 

Clinical Study Protocol 
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Study Code: RhoVac-001 
Date: 07 November 2017 
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Confidential 
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The adjuvant Montanide ISA 51 is a so called in-complete Freund’s adjuvant developed 
specifically for use as an adjuvant in therapeutic cancer vaccines. Montanide ISA 51 is 
supplied sterile, ready for use in single use vials of 3 mL. Montanide ISA 51 is defined as a 
mixture of a highly purified mineral oil (Drakeol 6VR) and a surfactant (Mannide monooleate). 
When mixed with an aqueous phase in a 50/50 ratio, it renders a water in oil emulsion.  
9.1.3 Packaging and Labelling of Investigational Medicinal Product 
The IMP RV001V will be supplied in kits containing the needed items for each administration: 
• 
One vial of RV001 Injection 0.2 mg/mL  
• 
One vial of Montanide ISA 51  
• 
Two 2 mL disposable syringes (Luer Lock) 
• 
Two vial adapters (13 mm, Luer Lock)) 
• 
One I-connector (Luer Lock) 
• 
One injection needle for subcutaneous injection (Luer Lock) 
• 
One syringe label 
• 
One plastic bag for collection of used materials 
RV001V will be supplied to the site in outer boxes, each containing 11 kits with content as 
described above. As the storage requirements for RV001 Injection 0.2 mg/mL and Montanide 
ISA 51 are different (see Section 9.1.4), RV001 Injection 0.2 mg/mL will be supplied in a 
separate carton labelled with the same kit number as the rest of the kit. 
Replacement kits will be available on request in case the whole or part of the kit is lost. 
9.1.4 Storage and Handling of Investigational Medicinal Product 
RV001 Injection 0.2 mg/mL must be stored in a refrigerator (2 – 8oC). Montanide ISA 51 must 
be stored at room temperature (15 – 30oC). For further information on expiry date of the two 
components of RV001V, reference is made to the product label. 
Following mixing and emulsification of the RV001 Injection 0.2 mg/mL and Montanide ISA 
51, the vaccine RV001V shall be administered immediately (less than 15 minutes). 
The vaccine is prepared and labelled by the Phase I clinic according the instructions that will 
be provided to the site.  
9.2 
Method of Assigning Patients to Treatment Groups 
All patients who have provided informed consent and meet all of the inclusion criteria and 
none of the exclusion will be assigned to treatment with the vaccine containing RV001. 
9.3 
Selection of Doses in the Study 
Traditionally, first-in-human clinical trials are generally conducted to identify the maximum 
tolerated dose or the biologically active dose using a dose-escalation design. This design 
may not be applied to cancer vaccines, given their unique mechanism of action. A cancer 
vaccine, in contrast to cytotoxic agents, generates its effect by modulating the immune 
system to target specific antigens on cancer cells. The selection of dose is based on 
previous experience, with peptide based vaccines, primarily from the Center for Cancer 
Immune Therapy at the University Hospital Herlev [40]. The general approach here has been 

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to use of 0.1 mg of the peptide. This mechanism of action requires that a certain exposure 
threshold is achieved [41, 42]  
From a safety point of view, it is recognized that peptide vaccines generally seem inherently 
safe as long as the adjuvants are used in combinations and doses previously demonstrated 
to be safe 
In addition, the completed repeated dose-toxicology study has shown that a dose 
(recalculated to Human Equivalent Dose) which is more than 400 times higher than the 
proposed could be administered to the animals without any indication of treatment related 
systemic toxicity. 
Based on this rationale the selected dose of RV001 to be used in the study is 0.1 mg.  
The dose (volume) of the adjuvant Montanide ISA 51 is reported to have been used in 
volumes from 0.1 mL to as high as 5.0 mL. From previous reported experience, a dose of 
approx. 0.5 mL of Montanide ISA 51 has shown to provide the required enhancement of 
antigen-specific immune responses [39, 40]. Hence, this target volume was also chosen for 
this trial.  
The other parameter defining the volume of Montanide ISA 51 to be used is the water droplet 
size in the emulsion, which preferably should be around 1 micrometre in diameter. 
Formulation studies have demonstrated that this droplet size is obtained when the ratio 
between RV001 Injection 0.2 mg/mL and Montanide ISA 51 is 50/50. 
In addition, Montanide ISA 51 was studied in a repeated dose toxicological study, both in 
combination with RV001 and alone. Local reactions at injection sites were noticed and these 
reactions are known and reported reactions linked to the use of Montanide ISA 51. 
Administration of 1 mL of RV001V will provide a dose of 0.1 mg RV001 and 0.5 mL 
Montanide ISA 51. 
9.4 
Selection and Timing of Dose for Each Patient 
There are no general consensus on the dose regiment for peptide vaccines. The dose 
regiment selected for this study is based on previous experience with similar peptide 
vaccines [40]. 
9.5 
Blinding 
This is an open-label study with no control arm.  
9.6 
Prior and Concomitant Therapy 
Supportive treatment is given based on a clinical judgement and should be noted in the 
patient chart in accordance with existing practice. However, concomitant medication 
administered during the study may lead to withdrawal of the patient from the study (see 
Section 8.5). 
The following medications and treatments are prohibited during the study:  
• 
Chemotherapy and radiotherapy is prohibited from 12 weeks before the first 
vaccination and until 4 weeks after the last vaccination. 
• 
For ADT; please see Section 8.5.1 
• 
Immunosuppressive therapy. Use of inhaled steroids, nasal sprays, and topical 
creams for small body areas is allowed.  

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The use of all medication by the patient must be recorded in the appropriate sections of the 
CRF. 
9.7 
Treatment Compliance 
RV001 vaccination will be administered at the Phase I Unit and by the staff under controlled 
conditions. The time of administration and the initials of the person administering the vaccine 
will be documented in the CRF and in the accountability log. 
9.8 
Drug Accountability 
The drug accountability will be performed by checking the used vials containing RV001 and 
the drug accountability log. 

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10 
STUDY ASSESSMENTS 
10.1 Primary and Secondary Endpoints 
Primary endpoint 
The primary endpoint of the study is the proportion of patients developing treatment related 
grade 3, 4 or 5 toxicity in accordance with CTCAE, with the exception of fever. The study will 
be terminated if this toxicity is observed in more than 1 of the first 6 patients, i.e. in ≥33.3% of 
the patients. The study will be considered meeting the primary endpoint if the proportion of 
patients with this toxicity at the end of the study is not higher than 33.3%. 
In addition, the tolerability will be evaluated by number of patients who discontinue the study 
treatment prematurely. The safety will be evaluated with frequency and severity of AEs. The 
numbers and proportions of patients with any treatment-emergent adverse event (TEAE), 
and any serious TEAE will be summarised. Furthermore, changes in vital signs, laboratory 
variables, physical examination and ECG will be evaluated. 
Secondary endpoints 
For the evaluation of the immunological effect of the vaccinations, patients will be followed 
with in-vitro analysis of antigen specific T-cell reactivity against RhoC and possibly other 
antigens as well.  
To monitor RV001V-specific T-cells in treated patients, and thereby the immunological 
response, the immunogenicity of RV001 in patients is determined by measuring anti-vaccine 
T cells before, during and after vaccination and by evaluating the changes from baseline (last 
assessment before the first vaccination) to each vaccination and follow-up visit. The 
measurements are done on immune cells isolated from the collected blood and frozen in a 
research biobank. 
All patients will be tested using IFNgamma enzyme-linked immunospot (ELIspot) assay. For 
ELIspot positive patients, intracellular staining (ICS) for dissecting CD4/CD8 responses and 
cytokine production profile will be performed. The ICS markers will be CD4/CD8/dead cell 
dye/ Interleukin-2(IL-2)/IFNgamma/TNF/CD154/CD107a. As a minimum for patients that are  
HLA-A3 positive, multimer staining for assessing RV001V-specific cells will be performed. 
For selected patients, advanced functional analysis of RV001V-specific T-cells may be 
performed.  
Exploratory endpoints 
The PSA levels will be evaluated by: 
• 
Changes from baseline in the PSA levels among the patients with measurable levels 
at baseline (the last PSA assessment before the first vaccination) 
• 
Number of patients with measurable PSA levels at baseline and at each vaccination, 
where measured and follow-up visit. 
The potential association between the PSA levels and immunological response will be 
evaluated by: 
• 
Anti-vaccine T cell levels classified by the PSA status (measurable or non-
measurable) at baseline and at each vaccination where PSA is measured and follow-
up visit 

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• 
Correlation of changes from baseline in anti-vaccine T cell levels and PSA levels 
among the patients with measurable PSA levels at baseline. 
PFS and OS will be evaluated as time from baseline (time of the first vaccination) to the 
event. For PFS, disease progression or death for any reason will be defined as an event. For 
OS, death for any reason is defined as an event. The data from the patients without an event 
will be censored at the last time when the patient is known to be free of disease progression 
or alive. 
10.2 Sampling Procedures, Handling and Storage 
Blood Tests for Lymphocyte Evaluation 
Blood samples of 100 mL heparinized blood and 8 mL blood in a dry glass will be drawn for 
lymphocyte function evaluation and 8 mL for HLA determination in accordance with the 
treatment schedule, as described in Section 7.2.1 and Table 1 and Table 2. 
Immune cells will be isolated from the collected blood samples by use of 
Leucosep/Lymphoprep-technique and peripheral blood mononuclear cell samples and serum 
will be stored at -150°C or below and sent to the University of Tübingen in Germany for 
analysis at intervals as agreed with the sponsor. Until shipment, the blood collected for 
lymphocyte evaluation will be stored at Zelo Phase I Unit and constitute a research biobank. 
The material will be kept at the laboratory in Tübingen for up to 5 years for potential further 
research in relation to the study. Thereafter the samples will be destroyed. After shipment to 
the University of Tübingen, the blood collected will be handled according to German laws.  
A new approval from the Danish Data Protection Agency will be obtained should we wish to 
use the samples for other research areas.  
All patient data will be transferred in a coded form in these cases. The biological material will 
be destroyed if the patient withdraws his/her consent and does not want the material to be 
used. In this case, no further analysis will be made on the collected material. Results of 
analyses already performed will, however, not be discarded. 
10.3 Bioanalytical Method 
Lymphocyte Evaluation  
Antigen-specific immune reactivity will be tested by use of a panel of relevant immunological 
assays that may include ELIspot, enzyme linked immunosorbent assay (ELISA), proliferation 
assays, cytotoxic assays, ICS, and multimer staining of RhoC-specific CD8 T-cells (in 
patients carrying the HLA-A03.01 molecules).  
10.4 Demographic and Other Baseline Characteristics 
10.4.1 Demographic and Baseline Data 
The following demographic and baseline data will be collected at the screening visit/Visit 1b: 
• 
Date of birth 
• 
Sex 
• 
Ethnicity 
• 
Weight and height 
• 
Physical Examination 

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10.4.2 Medical History 
Medical history will be recorded at the screening visit/Visit 1a (and confirmed at Visit 1b). 
10.4.3 Prior and Concomitant Medication 
Prior medications taken within 1 month prior to screening will be recorded at the screening 
visit.  
Concomitant medication will be recorded on the concomitant medication log/page of the CRF 
throughout the study. 
10.5 Safety Assessments 
10.5.1 Safety Variables 
The following safety variables will be measured: 
• 
AEs 
• 
Vital signs 
• 
Physical examination 
• 
ECG 
• 
Laboratory safety assessments  
10.5.2 Adverse Events 
AEs will be recorded during the study period from the first dose of vaccine to the completion 
of the follow-up Visit 13. During the follow-up phase visit 14-17 only study/protocol related 
AEs and SAEs suspected to be related to the vaccination will be recorded. For further 
information of definitions and reporting of AEs and SAEs, see Section 11.  
10.5.3 Physical Examination 
All patients will undergo a standard physical examination.  
The timing of the assessments is described in Section 7.2.1 and Table 1. 
10.5.4 Vital Signs 
The following vital signs will be monitored as safety variables: 
• 
Resting systolic and diastolic blood pressure (mmHg), after at least 5 minutes rest in 
supine position 
• 
Resting pulse (beats per minute), after at least 5 minutes rest in supine position 
• 
Body (e.g., tympanic or temporal artery) temperature (°C) 
The observed values will be recorded and assessed as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
The timing of the assessments is described in Section 7.2.1 and Table 1. 
10.5.5 Electrocardiogram 
A standard 12-lead ECG will be recorded after the patient has rested in supine position for at 
least 5 minutes. 

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The observed values will be recorded and assessed as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
The timing of the assessments is described in Section 7.2.1 and Table 1. 
10.5.6 Laboratory Safety Assessments 
The laboratory safety analyses (haematology, clinical chemistry and urinalysis) will be 
performed by Department of Clinical Biochemistry at Bispebjerg Hospital. The analysis will 
be done immediately (typically on the day of collection) and any remaining material will be 
discarded immediately after analysis. 
The following laboratory safety parameters will be measured (Table 3): 
Table 3 
Laboratory Safety Parameters 
Category 
Laboratory Parameter 
Haematology 
Haemoglobin, RBCs, haematocrit, leukocytes and differential 
counts, platelets (3 ml) 
Clinical Chemistry 
Sodium, potassium, calcium, creatinine, albumin, LDH, alkaline 
phosphatase, ASAT, ALAT, total bilirubin, CRP (4 ml) 
Blood glucose (3 ml, only at screening) 
HbA1c (3 ml, only at screening) 
Serology 
Hepatitis B core antibody, hepatitis B surface antigen, hepatitis C 
virus (4 ml, only at screening) 
HIV (4 ml, only at screening) 
Urinalysis 
Glucose, bilirubin, ketones, specific gravity, blood, pH, protein, 
urobilinogen, nitrite, leucocytes 
 
The observed values will be recorded and assessed as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
The timing of the assessments is described in Section 7.2.1 and Table 1. 
10.5.7 Other Safety Measurements  
Injection site reactions will be recorded. 
10.6 PSA Measurements 
PSA analysis will be performed by Department of Clinical Biochemistry at Bispebjerg 
Hospital. The analysis will be done immediately (typically on the day of collection) and any 
remaining material will be discarded immediately after analysis. 
The timing of the assessments is described in Section 7.2.1 and Table 1. A volume of 4 mL 
will be collected at each time point. 
10.7 Total Blood Volumes 
The total volume of blood taken during the study will be approximately 1000 mL. This 
includes all safety laboratory assessments, cancer specific assessment (PSA) and 
immunological assessments. 

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For details of blood volumes, see Appendix B 
The total amount of blood collected in this study corresponds to approximately to two blood 
donations during a period of approximately 20 months. This is considered acceptable. 
Furthermore, the haemoglobin, RBC count, and haematocrit are measured at frequent 
intervals during the study, allowing the investigator to take appropriate measures (e.g., to 
decide not to collect blood for lymphocyte evaluation at some visits) in case the patient 
shows early signs of anaemia. 
 
10.8 Appropriateness of Measurements 
Standardised methods for measurements of safety variables and analysis of PSA (such as 
Electrochemiluminescence Immunoassay will be used. For analysis of immune response, 
state of the art assays and methodology will be used as described in Section 10.3. 
 

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11 
ADVERSE EVENTS 
11.1 Definitions 
11.1.1 Adverse Event 
Any untoward medical occurrence in a patient or clinical trial patient administered a medicinal 
product and which does not necessarily have a causal relationship with this treatment. 
Comment: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
IMP, whether or not considered related to the IMP. 
11.1.2 Adverse Reaction 
All untoward and unintended responses to an IMP related to any dose administered. 
Comment: All AEs judged by either the Investigator or the Sponsor as having a reasonable 
causal relationship to a medicinal product qualify as adverse reactions. The expression 
reasonable causal relationship means to convey in general that there is evidence or 
argument to suggest a causal relationship. 
11.1.3 Unexpected Adverse Reaction 
An adverse reaction, the nature or severity of which is not consistent with the applicable 
product information (e.g. Investigator's Brochure for an unauthorised IMP or summary of 
product characteristics for an authorised product). 
Comment: When the outcome of the adverse reaction is not consistent with the applicable 
product information this adverse reaction should be considered as unexpected. 
11.1.4 Serious Adverse Event 
Any untoward medicinal occurrence or effect that at any dose: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalisation or prolongation of existing hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
Comments: Life-threatening in the definition of an SAE or serious adverse reaction (SAR) 
refers to an event in which the patient was at risk of death at the time of event; it does not 
refer to an event which hypothetically might have caused death if it was more severe. 
Medical judgement should be exercised in deciding whether an adverse event/reaction is 
serious in other situations. Important adverse events/reactions that are not immediately life-
threatening or do not result in death or hospitalisation but may jeopardise the patient or may 
require intervention to prevent one of the other outcomes listed in the definition above, 
should also be considered serious. 
11.1.5 Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is an AE that is assessed as 
serious, related and unexpected. 

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11.2 Reporting of Adverse Events 
All study patients will be carefully monitored for the occurrence of AEs during the study 
period from the first vaccination to the completion of the follow-up visit (Visit 13). During the 
follow-up phase visit 14-17 only study/protocol related AEs and SAEs suspected to be 
related to the vaccination will be recorded The Investigator will collect AEs with a non-leading 
question such as “have you experienced any new health problems or worsening of existing 
conditions” as well as reporting events directly observed or spontaneously volunteered by 
patients. 
Clearly related signs, symptoms and abnormal diagnostic procedure results should be 
grouped together and reported as a single diagnosis or syndrome whenever possible. 
All AEs including but not limited to events reported by the patient, or reported in answer to an 
open question by the Investigator or member of this team, which fall into any of the above 
definitions must be recorded as an AE in the CRF and should include the following 
information: 
• 
Brief description of the event (diagnosis) 
• 
Start date (and time, if relevant) 
• 
Stop date (and time, if relevant) (or resolution) 
• 
Severity 
• 
Action taken regarding study drug 
• 
Opinion on causality 
• 
Seriousness 
• 
Outcome 
Severity 
Grading of Adverse Events 
The severity of an AE refers to the intensity of the reaction. 
Events are graded using CTCAE version 4.03 [43].  
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• 
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL)1. 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL2. 
• 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
                                               
 
 
1 Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
2 Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 

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• 
Grade 5: Death related to AE 
Patients experiencing AEs will be monitored with the relevant clinical evaluations and 
laboratory investigations assessed by the attending physician. All AEs must be monitored 
until satisfactory restitution or stabilization. Results of the monitoring must be recorded in the 
patient chart and electronic CRF (eCRF). 
If an AE changes in severity, the worst severity should be reported. 
Causality 
Causality will be assessed as: 
Probable 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the IMP, 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 fulfil this definition. 
Possible 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the IMP, but which could also be explained by concurrent disease or other 
drugs or chemicals. Information on IMP withdrawal may be lacking or unclear. 
Unlikely 
A clinical event, including laboratory test abnormality, with a temporal relationship to IMP 
administration which makes a causal relationship improbable, and in which other drugs, 
chemicals or underlying disease provide plausible explanations. 
Follow-up of Patients after Adverse Events 
Any AE that is ongoing when the patient is withdrawn from the study should be followed up 
until the AE is resolved or the Investigator decides that the AE is stable and needs no further 
follow-up. The date when the Investigator considers one of these outcomes to have occurred 
for the last ongoing AE for a patient will be considered the last visit for this patient, and the 
outcome should be recorded in the CRF. 
Abnormal Laboratory Values/Vital Signs 
The reporting of abnormalities as both laboratory/vital signs findings and AEs should be 
avoided. 
An asymptomatic abnormal laboratory/vital sign finding should only be reported as an AE if it 
is clinically significant, if it fulfils the criteria for an SAE or if it causes the patient to 
discontinue the study. 
If an abnormal laboratory/vital sign value is associated with clinical signs and symptoms, the 
sign/symptom should be reported as an AE and the associated laboratory/vital sign result 
should be considered additional information. 
11.3 Reporting of Serious Adverse Events 
The Investigator is responsible for ensuring that all SAEs are reported to the Sponsor 
immediately, but in any event no later than 24 hours of any site staff becoming aware of the 
event. Initial reports should be followed as soon as possible by detailed written reports. The 

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initial and follow-up reports should identify patients by unique code numbers assigned in the 
study. The patients’ names, personal identification numbers, and/or addresses must not be 
included. The following information is mandatory for the initial report: 
• 
Patient study ID 
• 
Study treatment (blinded, if applicable) 
• 
Start date (time, if relevant) of the study treatment 
• 
Brief description of the event (diagnosis) 
• 
Start date (time, if relevant) of the event 
• 
Seriousness criteria 
• 
Causality assessment 
For reported deaths, the Investigator should supply the Sponsor and the IEC (if applicable) 
with any additional requested information (e.g. autopsy reports and terminal medical reports). 
SAE REPORTING CONTACT DETAILS 
TFS 
Drug Safety 
Fax:  
+46 (0) 46 280 19 19 
Phone: +46 (0) 46 280 18 00 (switchboard) 
E-mail: safety.tfs@tfscro.com 
 
Note: If there is local legislation requiring Investigators to report AEs to the CA or the IEC, 
the Investigator should also comply with this legislation. If any such reporting is planned, this 
must be stated in the SAE report, and once the reporting has been performed, a copy of the 
reporting documentation must be enclosed with the follow-up SAE report to the Sponsor. 
11.4 Reporting of Suspected Unexpected Serious Adverse Reactions 
The Sponsor is responsible for informing the CA(s), the European Medicines Agency and 
IEC(s) of any individual case reports of SAEs that are determined to be reportable by the 
Sponsor (i.e. SUSARs). The Investigator will ensure that all relevant information is provided 
to the Sponsor to allow the Sponsor to meet their obligations to report the SUSAR to the CA 
and IEC. For a SUSAR that is fatal or life-threatening, this should be reported as soon as 
possible and not later than 7 days after the Sponsor was first advised, for any other SUSAR 
this should be within 15 days. 
11.5 Adverse Events of Special Interest 
Treatment is terminated if AEs occur that are of a degree that makes completion of the study 
impossible, e.g., treatment related grade 3 or 4 toxicity in accordance with CTCAE (except 
for transient (< 48 hours) fever, fatigue, headache, flue like symptoms). 

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11.6 Precautions/Overdose 
There is no known antidote to RV001V. In the event of overdose symptomatic management 
is indicated. 
11.7 Pregnancy 
Male patients will be instructed to notify the Investigator immediately if their partner becomes 
pregnant.  
A pregnancy as such is not an AE, unless there is a possibility that the IMP has interfered 
with the efficiency of any contraceptive measures. However, the Investigator should report 
pregnancies according to the procedures and timelines described for reporting of SAEs 
(Section 11.3). The pregnancy report form should be used instead of the SAE form. 
The pregnant partner will be followed until the end of the pregnancy. Any complication during 
the pregnancy should preferably be reported as an AE. The outcome of the pregnancy must 
be reported on the pregnancy report form. Any spontaneous abortion, stillbirth, birth 
defect/congenital anomaly, death, or other serious infant condition must be reported and 
followed up as an SAE. 

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12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
12.1 Statistical and Analytical Plans 
The first version of the Statistical Analysis Plan (SAP) for this open-label study will be 
finalized before the first vaccination. The first SAP version can either be a stand-alone 
document or this section of the study protocol. Subsequent versions of the SAP may be 
developed during the course of the study. The final SAP will be finalised before locking the 
study database. 
12.1.1 Data Sets to be Analysed 
All patients who received at least one vaccination will be included in the statistical analyses. 
A subset analysis will be done on selected variables among the patients who received 3, 6 
and all 11 vaccinations. Additional subgroup analyses may be performed as defined in the 
SAP. 
12.1.2 Statistical Issues 
Level of Significance, Multiple Comparisons and Multiplicity 
No formal statistical testing is planned. The confidence intervals will be calculated with 
2-sided 95% coverage. 
Adjustment for Covariates 
No adjustments for covariates are planned. 
Handling of Dropouts and Missing Data 
The study data will be primarily evaluated as observed cases. For continuous endpoints, 
likelihood-based modelling approach, e.g. Mixed Model for Repeated Measures (MMRM) 
may be used to handle incomplete data.  
Examination of Subgroups 
Subgroup analyses may be defined in the SAP. 
Data Monitoring 
This is an open label study. 
12.1.3 Summary Statistics 
In general, data will be summarised by means of summary statistics. Continuous data will be 
presented with the number of observations, mean value, standard deviation, standard error 
of the mean, minimum, Q1, median, Q3 and maximum value. Categorical data will be 
presented as counts and percentages. The data will be presented by visit.  
Individual patient data will be listed.  
12.1.4 Analysis of the Primary Endpoint 
The primary endpoint of the study is the proportion of patients developing treatment related 
grade 3, 4 or 5 toxicity in accordance with CTCAE, with the exception of fever and local 
reactions that can be attributed to the vaccine. The study will be terminated if this toxicity is 

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observed in more than one of the first 6 patients, i.e. in <33.3% of the patients. The study will 
be considered meeting the primary endpoint if the proportion of patients with this toxicity at 
the end of the study is not higher than 33.3%. The primary endpoint will be evaluated by 
calculating the percentages of patients with the toxicity as defined above out of all patients 
who got at least one vaccination. In addition to the percentage, an exact 95% confidence 
interval will be calculated using the Clopper-Pearson method. 
The tolerability will be evaluated by number of patients who discontinue the study treatment 
prematurely. The following will be reported: 
• 
Number and proportion of patients who discontinue the study prematurely 
• 
Reasons for premature discontinuation 
• 
Number of vaccination received prior to the premature discontinuation 
• 
The time from the first vaccination to premature discontinuation illustrated with a 
Kaplan-Meier plot. In this analysis, the patients who do not discontinue the study 
prematurely will be censored at the time of the last visit. 
AEs will be captured and graded by CTCAE. All AEs captured during the study will be coded 
with the Medical Dictionary for Regulatory Activities (MedDRA). TEAEs are defined as signs 
or symptoms that emerge after the first vaccination, including those signs and symptoms that 
are absent pre-vaccination or that have worsened relative to the pre-vaccination status. 
TEAEs will be summarized by MedDRA system organ class (SOC) and preferred term (PT). 
Both event and patient counts, where applicable, will be summarized. The counts will be 
complemented by percentages calculated for the patient counts unless otherwise specified. 
The following summaries will be produced: 
• 
An overall summary of the number and percentage of patients reporting TEAEs and 
the number of TEAE events, drug-related TEAEs, severe TEAEs, serious TEAEs, 
TEAEs leading to premature study treatment discontinuation and TEAEs leading to 
death 
• 
TEAEs by SOC and PT, both as event and patient counts 
• 
TEAEs by PT, both as event and patient counts, sorted in descending frequency of 
the events 
• 
TEAEs by SOC, PT, and relationship to study treatment, as event counts only 
(percentages calculated as % of total number of reported events) 
• 
TEAEs by SOC, PT, and severity, as event counts only (percentages calculated as % 
of total number of reported events) 
• 
Serious TEAEs by SOC and PT, both as event and patient counts 
• 
TEAEs leading to study treatment discontinuation, both as event and patient counts 
• 
TEAEs leading to death, both as event and patient counts 
The time course of the most frequent TEAEs will be described as a function of the number of 
vaccinations / as a function of time: 
• 
The time to first onset of the most frequent TEAEs (on PT level) will be classified 
based on the number of vaccinations received prior to the onset (after the first and 
before the second vaccination, after the second and prior to the third vaccination, 
etc.). In addition, the time curves will be illustrated with Kaplan-Meier plots, in which 
the patients without the TEAE in question will be censored at the time of the last visit. 

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• 
Increases or decreases of the TEAE incidence over time will be illustrated with plots 
of mean cumulative frequencies of the TEAEs as function of time, calculated using 
Proportional Means Regression model for recurrent data, allowing the count of 
multiple events per patient. This analysis will be performed for the most frequent 
TEAEs (on PT level, for event level data). 
The pre-vaccination vital signs at baseline, each vaccination and follow-up visit and changes 
from baseline to each vaccination and follow-up visit will be summarized with descriptive 
statistics. In addition, the changes from pre-vaccination to post-vaccination will be 
summarized for visits at which post-vaccination vital signs are captured. 
The physical examination findings will be summarized by body system using shift tables. The 
shift table includes columns for baseline data (normal or abnormal) and rows for each post-
baseline visit (normal or abnormal). 
All collected ECG data will be summarized. In addition, the corrected QT (QTc) times will be 
derived using both the formula by Bazett (QT * [60/HR]1/2) and by Fridericia (QT * [60/HR]1/3). 
The pre-vaccination ECG parameters at baseline, each vaccination and follow-up visit and 
changes from baseline to each vaccination and follow-up visit will be summarized with 
descriptive statistics. In addition, the changes from pre-vaccination to post-vaccination will be 
summarized for visits at which post-vaccination ECG data are captured. 
In addition, the following categorical analyses will be performed at each visit/time point: 
- 
Clinical interpretation: proportion of ECGs which are normal, abnormal and not clinically 
significant or abnormal and clinically significant (as shift table by visit) 
- 
Proportion of clinically significantly abnormal QTc values, defined as values ≤450 ms, 
>450 – 480 ms, >480 – 500 ms, and >500 ms (as shift tables by visit, separately for 
QTcB and QTcF) 
- 
Proportion of clinically significantly abnormal changes in QTc values from baseline, 
defined as changes >30 msec or >60 msec (as frequency tables by visit, separately for 
QTcB and QTcF). 
The safety laboratory at baseline, each vaccination and follow-up visit and changes from 
baseline to each vaccination and follow-up visit will be summarized with descriptive statistics. 
The number and proportion of normal/abnormal values will be summarized with shift tables.  
 
12.1.5 Analysis of Secondary Endpoints 
For the evaluation of the immunological effect of the vaccinations, patients will be followed 
with in-vitro analysis of antigen specific T-cell reactivity against RhoC and possibly other 
antigens as well.  
To monitor specific RV001V T-cells in treated patients, and thereby the immunological 
response, the immunogenicity of RV001 in patients is determined by measuring anti-vaccine 
T cells before, during and after vaccination and by evaluating the changes from baseline (last 
assessment before the first vaccination) to each vaccination and follow-up visit. These values 
will be summarized with descriptive statistics by visit. In addition, MMRM may be used to 
estimate the changes from baseline with 95% confidence intervals. 
All patients will be tested using IFNgamma ELIspot assay. For ELIspot positive patients, ICS 
staining for dissecting CD4/CD8 responses and cytokine production profile will be performed. 
The ICS markers will be CD4/CD8/dead cell dye/IL-2/IFNg/TNF/CD154/CD107a. For 
minimum all HLA-A3 positive patients, multimer staining for assessing specific RV001V cells 

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will be performed. For selected patients, advanced functional analysis of RV001V specific 
T-cells may be performed. 
If feasible, the ICS markers at baseline, each vaccination and follow-up visit will be 
summarized with descriptive statistics. In addition, the changes from baseline will be 
summarized.  
In addition, thresholds for immunological response may be defined and the proportions of 
patients above or below the thresholds will be summarized by visit. 
12.1.6 Analysis of Exploratory Endpoints 
The PSA levels will be evaluated by: 
• 
Among the patients with measurable PSA levels at baseline: the PSA values at 
baseline, at each vaccination and follow-up visit will be summarized with descriptive 
statistics. In addition, the changes from baseline will be summarized. If feasible, the 
changes from baseline may be estimated with MMRM, including 95% confidence 
intervals for the changes. 
• 
Number of patients with measurable PSA levels at baseline and at each vaccination 
and follow-up visit will be summarized with a shift table. 
The potential association between the PSA levels and immunological response will be 
evaluated by: 
• 
Anti-vaccine T cell levels classified by the PSA status (measurable or non-
measurable) at baseline and at each vaccination and follow-up visit will be 
summarized with descriptive statistics 
• 
Correlation of changes from baseline in anti-vaccine T cell levels and PSA levels 
among the patients with measurable PSA levels at baseline will be illustrated with 
scatter plots and by calculating correlation coefficients (e.g. Spearman’s correlation 
coefficient). 
The PFS and OS will be evaluated as time from baseline (time of the first vaccination) to the 
event. For PFS, disease progression or death for any reason will be defined as an event. For 
OS, death for any reason is defined as an event. The data from the patients without an event 
will be censored at the last time when the patient is known to be free of disease progression 
or alive. The data will be summarized as Kaplan-Meier plots. 
12.1.7 Demographic and Other Baseline Characteristics 
Patient disposition, demographic and other baseline data will be presented using summary 
statistics.  
12.1.8 Exposure to Treatment 
Exposure to the study treatment will be summarized as number of vaccinations received. The 
data will be summarized as cumulative number of patients receiving at least 1, 2, and so 
forth up to 11 vaccinations. 
In addition, the cumulative dose vaccinated will be summarized. 
12.1.9 Concomitant Treatment 
Concomitant medication and concomitant therapy will be summarised as number of patients 
being treated with each type of medication/therapy classified according to ATC level 1 and 
World Health Organization (WHO) Drug Dictionary preferred term.  

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12.2 Determination of Sample Size 
The study is designed as a phase I/IIa trial and the primary objective is to determine safety 
and tolerability related to the treatment. A 3+3 design is a standard design to assess the 
safety and tolerability in dose-response oncology studies. As the present study is a 
vaccination study not assessing dose-response and only one dose level will be tested, 
additional patients are included to improve the precision of the evaluation of the safety and 
tolerability. It is judged that 10 patients is sufficient for such evaluation. 
The expected variability of the measurements associated with the primary objective is 
unknown. The number of patients needed is therefore uncertain. It is judged that 10 patients 
(fully evaluable) is a relevant number to meet the primary objective of the study.  
For evaluation of immune response of the treatment, the variability is unknown. An adequate 
sample size to provide sufficient information can therefore not be estimated, however from 
previous experiences of early clinical trials, it is found appropriate to evaluate up to 
20 patients. Given a dropout rate of some 20% the total number of patients that may be 
included is set to 25. 
All patients, who are included and treated with at least one dose of RV001V and in 
accordance with the protocol, will be part of the safety analyses.  
12.3 Procedures for Reporting any Deviation(s) from the Original Statistical Analysis 
Plan 
Any deviation(s) from the original statistical analysis plan (as described in the study protocol 
or in the SAP) will be described and justified in a protocol amendment and/or in a revised 
SAP and/or in the final report, as appropriate. 
12.4 Interim Analysis 
A formal interim analysis is not planned for this study. Evaluation of safety will be conducted 
as described in Section 7.1.1. Results from immune analysis will be evaluated during the 
study. 
 

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13 
INVESTIGATOR/SPONSOR RESPONSIBILITIES 
13.1 Ethics 
13.1.1 Independent Ethics Committee (IEC) 
This protocol and any amendments will be submitted to a properly constituted IEC, in 
accordance with the International Conference on Harmonisation (ICH) guidelines, the 
applicable European Directives and local legal requirements, for approval/favourable opinion 
of the study. Approval/favourable opinion must be obtained in writing before the first patient 
can be recruited. 
13.1.2 Ethical Conduct of the Study 
The study will be conducted in compliance with the protocol, regulatory requirements, good 
clinical practice (GCP) and the ethical principles of the latest revision of the Declaration of 
Helsinki as adopted by the World Medical Association. 
13.1.3 Patient Information and Consent (Appendix C) 
All patients will receive written and verbal information regarding the study at a prior interview. 
This information will emphasise that participation in the study is voluntary and that the patient 
may withdraw from the study at any time and for any reason. All patients will be given the 
opportunity to ask questions about the study and will be given sufficient time to decide 
whether to participate in the study. 
Before any study-related procedures the informed consent form will be signed and personally 
dated by the patient (or their legally acceptable representative and/or witness, as applicable) 
and by the person who conducted the informed consent discussion. 
A copy of the patient information including the signed consent form will be provided to the 
patient. 
13.2 Patient Records and Source Data 
No data will be recorded directly in the CRF. The origin of source data in the study will be 
specified for the Phase I unit and the hospital in separate documents (“Origin of Source 
Data”).  
It is the responsibility of the Investigator to record essential information in the medical 
records in accordance with national regulations and requirements.  
 
The following information should be included as a minimum in the medical records at 
the hospital: 
• 
A statement that the patient is in a clinical study 
• 
The identity of the study e.g. Study code 
• 
That informed consent was obtained and the date 
 
In addition the investigator at the hospital will fill in a study specific Form for 
determination of cancer status (stable disease or progression). A copy of the Form 
will be kept at the hospital and the original will be sent to the phase I unit. 

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The following information should be included as a minimum in the medical records at 
the Phase I unit: 
• 
A statement that the patient is in a clinical study 
• 
The identity of the study e.g. Study code 
• 
Patient screening number and/or patient number 
• 
That informed consent was obtained at the hospital and the date (verified by a copy of 
the signed consent Form) 
• 
Dates of all visits during the study period 
• 
Any information relating to AEs 
• 
All treatments and medications prescribed/administered (including dosage) 
• 
Date of study termination 
• 
Patient health service identification number (CPR) 
In addition to the medical records the phase I unit will use “work sheets” to record data. The 
Investigator is responsible for ensuring the accuracy, completeness, legibility and timeliness 
of the data recorded in the CRFs. Data reported in the CRF that are derived from source 
documents should be consistent with the source documents or the discrepancies should be 
explained. Signed sections of CRFs will be monitored and collected on a regular basis. 
13.3 Access to Source Data and Documentation 
The Investigator should guarantee access to source documents for the monitor and auditors 
as well as for inspection by appropriate regulatory agencies, and the IEC, if required. In 
addition, the monitor, the principal investigator at Zelo Phase I Unit, and the investigator at 
the Department of Urology at Rigshospitalet will have access to the patient’s entire medical 
records at the Department of Urology at Rigshospitalet. The aforementioned parties will also 
have access to all study-specific notes made about the patient in the study files at Zelo 
Phase I Unit. 
13.4 Monitoring 
The monitor will visit the study site (both clinics) on a regular basis to ensure that the study is 
conducted and documented in accordance with this protocol, ICH GCP guidelines, regulatory 
requirements and any study specific documents such as CRF completion guidelines. 
Monitoring visits will be conducted to confirm that e.g.: 
• 
The investigational team is adhering to the study protocol 
• 
Informed consent has been obtained from all participants 
• 
AEs have been reported as required 
• 
Data are being accurately recorded in the CRFs 
• 
IMP is being stored correctly and drug accountability is being performed on an on-
going basis 
• 
Facilities are, and remain, acceptable throughout the study 

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• 
The Investigator and the site are receiving sufficient information and support 
throughout the study 
Moreover, during monitoring visits the data recorded in the CRFs, source documents and 
other study-related records will be compared against each other in order to ensure accurate 
data that reflect the actual existence of the patient in the study i.e. source data verification. 
13.5 Data Management 
Data management and handling of data will be conducted according to the study specific 
Data Management Plan with ICH guidelines and TFS standard operating procedures (SOPs). 
Viedoc, an eCRF system, will be used to capture data from the study. Data entry will be 
performed by the study site personnel. Validation and data queries will be handled by the 
TFS Data Management Team. The data will be subjected to validation according to TFS 
SOPs in order to ensure accuracy in the collected eCRF data. 
Changes to the data in the eCRF will be made at the site by the study site personnel. The 
eCRF will have an audit trail with appropriate functionality for data capture, tracking and 
documentation of any queries or changes. Electronic signatures will be used to lock the data 
and identify the person entering or changing the data. 
Before database closure a reconciliation will be performed between the SAEs entered in the 
safety database and the study database. After database closure, the database will be 
exported as SAS® data sets. 
Any deviations, i.e. discrepancies and additions from the process defined in the Data 
Management Plan, will be described in a study specific Data Management Report. 
13.6 Quality Assurance and Audit 
Audits or inspections, including source data verification, may be performed by 
representatives of TFS, the Sponsor, a CA and/or an IEC. 
13.7 Record Retention 
The Investigator/institution should maintain essential documents (as defined in ICH E6 GCP, 
Section 8) as required by the applicable regulatory requirement(s). The 
Investigator/institution should take measures to prevent accidental or premature destruction 
of the documents. 
Essential documents should be retained according to applicable regulatory requirements of 
the country(ies) where the product is approved, and/or where the Sponsor intends to apply 
for approval. 
It is the responsibility of the Sponsor to inform the Investigator/institution in writing as to when 
the documents no longer need to be retained.  
13.8 Protocol Deviations 
Deviations to the study protocol will be documented in a Protocol Deviation Log. 
The classification of patients into protocol violators will be made during a meeting before 
database lock. The classification will be mutually agreed between the Sponsor and TFS. 
Listings will indicate the allocation of patients by analysis set and the number of patients per 
analysis set will be recorded in the clinical study report. 

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Any Serious Breaches that substantially affect the integrity or the safety of the patients or the 
scientific validity of the study will be reported to the relevant authorities in accordance with 
local regulatory requirements 
13.9 Insurance 
The Sponsor must provide insurance or must indemnify (legal and financial coverage) the 
Investigator/the institution against claims arising from the study, except for claims that arise 
from malpractice, negligence or non-compliance with the protocol.  
Patients are covered by mandatory insurance as per the Danish law “Lov om klage- og 
erstatningsadgang inden for sundhedsvæsenet” (Complaint Access and Compensation 
Entitlement within the Health System), Consolidated Act No. 1113 of 07 July 2011, Chapter 
4. 
In addition, DanTrials has taken out an insurance at the Danish insurance company Tryg, 
covering injuries to research subjects caused by the study staff (“lægeansvarsforsikring”). 
Research subjects do not lose any legal rights or benefits they would otherwise have been 
entitled to by participating in the study. 
13.10 Report and Publication 
After completion of the study, a clinical study report will be prepared according to the ICH 
Guideline for Structure and Content of Clinical Study Reports (ICH E3). The report will be 
developed after all patients have performed the follow up visit 1 month after the last 
vaccination. An addendum to the report will be written when the last patient has had the last 
follow up visit (End of long-term follow up). 
All publications and presentations must be based upon the clinical study report.  
All information supplied by the Sponsor in connection with this study will remain the sole 
property of the Sponsor and is to be considered confidential information. No confidential 
information will be disclosed to others without obtaining prior written consent from the 
Sponsor and will not be used except in the performance of this study. 
The sponsor recognises the traditional freedom of scientists to publish and present promptly 
the results of their studies and the sponsor is committed to presenting or publishing the 
results of this study, both if the results are positive, inconclusive, or negative. The presented 
or published data should be done using clean, checked and validated data only, in order to 
ensure the accuracy of the results. 
If an Investigator wishes to publish results from this clinical study, written permission to 
publish must be obtained from the Sponsor in advance. As some of the information regarding 
the IMP and development activities at the Sponsor may be of a strictly confidential nature, 
the Sponsor must first review any publication manuscript prior to their submission to journals, 
meetings or conferences. 
The Sponsor may choose to publish or present data from this study. If an Investigator is 
offered authorship, he/she will be asked to critically review the article for important 
intellectual content and approve the version to be published. The Sponsor has the right to 
use the results for registration and internal presentation and for promotion of the Sponsor’s 
commercial interests. 

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13.11 
 Subject Confidentiality 
The Sponsor will ensure that the use and disclosure of protected health information obtained 
during this clinical study complies with the legislation related to the privacy and protection of 
personal information, among these the Danish law on protection of private information (“Lov 
om behandling af personoplysninger”) which implements the EU directive 95/46/EC. 
Individual patient medical information obtained as a result of this clinical study is considered 
confidential and disclosure of this information to third parties is prohibited. Such medical 
information may be given only after approval of the patient to the patient’s physician or to 
other appropriate medical personnel responsible for the patient’s well-being. 
The Sponsor affirms the patient’s right to protection against invasion of privacy. Only a 
patient identification number and/or initials will identify patient data retrieved by the Sponsor. 
This is a private research project and therefore exempted from notification to the Danish 
Data Protection Agency. 

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14 
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Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 65 of 74 
 
15 
SIGNATURES 
This Clinical Study Protocol is approved by: 
 
SPONSOR’S REPRESENTATIVE: 
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE: 
 
 
 
Jens Kristensen, MD, PhD 
Chief Medical Officer 
RhoVac AB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR at Zelo 
Phase I Unit:  
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE: 
 
 
 
Jesper Sonne, MD, DMSc 
Zelo Phase I unit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROJECT LEADER:  
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE: 
 
 
 
Kerstin Danielson 
RhoVac AB 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 66 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PROTOCOL AUTHORS:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE: 
 
 
 
Jens Kristensen,  
Chief Medical Officer 
RhoVac AB 
 
 
 
 
 
 
 
 
 
 
DATE: 
 
 
 
Catherine Heddle 
Medical Writer 
TFS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 67 of 74 
 
16 
CLINICAL STUDY PROTOCOL AGREEMENT FORM 
I have read the clinical study protocol entitled: A Phase I/II study of RV001V, a RhoC 
anticancer vaccine, against metastasis from solid tumours 
and verified that it contains all necessary information for conducting the study. 
I hereby confirm that: 
• 
I have carefully read and understood this clinical study protocol 
• 
my staff and I will conduct the study according to the study protocol and will comply 
with its requirements, including ethical and safety considerations. 
I understand that, should the Sponsor decide to prematurely terminate or suspend the study 
for whatever reason, such decision will be communicated to me in writing. Conversely, if I 
decide to withdraw from execution of the study I will immediately communicate such a 
decision to the Sponsor. 
I agree not to publish any part of the results of the study carried out under this clinical study 
protocol without consulting the Sponsor. 
 
Principal 
Investigator/Investigator:  
Date: 
 
Signature:  
 
 
 
 
 

Clinical Study Protocol 
Sponsor: RhoVac 
Version: Final, version 3 
Study Code: RhoVac-001 
Date: 07 November 2017 
EudraCT No.: 2016-004189-24 
Confidential 
Page 68 of 74 
17 
APPENDICES 
Appendix A: ECOG Function/Performance Status 
Appendix B: Sampling Blood Volumes 
Appendix C: Informed Consent Form  
Appendix D: Financial Arrangements