A Phase 1/Phase 2 Trial to Evaluate Safety, Immunogenicity and PSA Response of VTP-850 Prostate Cancer Immunotherapeutic in Men With Biochemical Recurrence After Definitive Local Therapy for Prostate Cancer
Phase: PHASE1
Conditions: Prostate Cancer
Sponsor: Barinthus Biotherapeutics

 
 
 
 
PCA001 Protocol v5.0, 18Apr2024 
 
Cover Page for ClinicalTrials.gov 
 
 
Official Title:   
A Phase 1/Phase 2 Trial to Evaluate Safety, Immunogenicity and PSA Response of VTP-850 
Prostate Cancer Immunotherapeutic in Men with Biochemical Recurrence after Deﬁnitive 
Local Therapy for Prostate Cancer 
 
 
NCT Number:   
NCT05617040 
 
Document Date: 
18 April 2024 
 
 

 
 
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TITLE PAGE 
 
Protocol Title: A Phase 1/Phase 2 Trial to Evaluate Safety, Immunogenicity and PSA Response 
of VTP-850 Prostate Cancer Immunotherapeutic in Men with Biochemical Recurrence after 
Definitive Local Therapy for Prostate Cancer 
Protocol Number: PCA001 Version 5.0 18 April 2024 
EudraCT Number: 2022-001479-14 
Compound: VTP-850 (ChAdOx1-PCAQ and MVA-PCAQ) 
 
Short Title: Prime-boost Immunotherapeutic Trial in Men with Biochemical Recurrence after 
Definitive Local Therapy for Prostate Cancer 
Trial Phase: Phase 1/Phase 2 
Sponsor Name: Barinthus Biotherapeutics (UK) Ltd. 
 
Legal Registered Address: 
Units 6 to 10 Zeus Building 
Rutherford Avenue 
Harwell Oxford 
Didcot 
OX11 0DF
 
 
Approval Date:  
 
Sponsor Signatory: 
 
 
VP Clinical Development 
 
Date 
 
Medical Monitor Name and Contact Information will be provided separately. 
 
 
18-APR-2024
18-APR-2024

 
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INVESTIGATOR AGREEMENT 
 
I, the undersigned, agree to conduct this study in accordance with this protocol, International 
Council on Harmonisation Good Clinical Practice (ICH GCP), the ethical principles set forth in 
the Declaration of Helsinki and with local regulatory requirements. 
 
Signature 
 
 
 
 
 
 
Date 
 
 
Printed Name  
 
 
 
 
 

 
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TABLE OF CONTENTS 
Title Page ........................................................................................................................................ 1 
INVESTIGATOR AGREEMENT.................................................................................................. 2 
Table of Contents ............................................................................................................................ 3 
List of Tables .................................................................................................................................. 6 
List of Figures ................................................................................................................................. 6 
1 
Protocol Summary ................................................................................................................. 7 
 
Synopsis ................................................................................................................ 7 
 
Schema ................................................................................................................ 14 
 
Schedule of Assessments .................................................................................... 15 
2 
Introduction ......................................................................................................................... 21 
 
Trial Rationale .................................................................................................... 21 
 
Background ......................................................................................................... 22 
 
Benefit/Risk Assessment .................................................................................... 22 
2.3.1 
Risk Assessment ................................................................................................. 23 
2.3.2 
Benefit Assessment ............................................................................................. 25 
2.3.3 
Overall Benefit-Risk Conclusion ........................................................................ 25 
3 
Objectives and Endpoints .................................................................................................... 26 
4 
Trial Design ......................................................................................................................... 27 
 
Overall Trial Design ........................................................................................... 27 
4.1.1 
Phase 1 – Dose/Regimen Finding Phase ............................................................. 28 
4.1.2 
Phase 2 – Main Phase ......................................................................................... 29 
4.1.3 
Selection of Phase 2 Regimen............................................................................. 29 
4.1.4 
Duration of Trial for Participants ........................................................................ 30 
4.1.5 
Safety Review During the Trial .......................................................................... 30 
4.1.6 
Pausing/Stopping Rules ...................................................................................... 30 
4.1.7 
Progression after Initial PSA Response .............................................................. 30 
 
Justification for Dose .......................................................................................... 31 
4.2.1 
Selection of ChAdOx1-PCAQ Target Dose ....................................................... 31 
4.2.2 
Selection of MVA-PCAQ Doses and Regimen .................................................. 32 
4.2.3 
Justification for Intravenous Administration of MVA-PCAQ ............................ 32 

 
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Scientific Rationale for Trial Design .................................................................. 33 
5 
Trial Population ................................................................................................................... 33 
 
Inclusion Criteria ................................................................................................ 33 
 
Exclusion Criteria ............................................................................................... 35 
 
Screen Failures .................................................................................................... 37 
 
End of Trial Definition ........................................................................................ 37 
6 
Trial Interventions and Concomitant Therapies .................................................................. 37 
 
Identity of Investigational Products .................................................................... 37 
 
Dose Levels Administered .................................................................................. 38 
 
Preparation, Handling, Storage, and Accountability........................................... 38 
 
Measures to Minimise Bias: Randomisation and Blinding ................................. 38 
 
Trial Intervention Compliance ............................................................................ 39 
 
Dose Modification .............................................................................................. 39 
 
Continued Access to Trial Intervention after the End of the Trial ...................... 39 
 
Overdose or Incorrect Administration ................................................................ 39 
 
Rescue Medicine ................................................................................................. 39 
 
Prior and Concomitant Medications ................................................................... 39 
 
Contraindications/Delay to Dosing ..................................................................... 40 
 
Delay to Dosing Due to Study Pause .................................................................. 41 
7 
Discontinuation of Trial Intervention and Participant Discontinuation or Withdrawal ...... 41 
 
Discontinuation of Trial Intervention ................................................................. 41 
 
Participant Discontinuation/Withdrawal from the Trial ..................................... 41 
 
Lost to Follow-up ................................................................................................ 42 
8 
Trial Assessments and Procedures ...................................................................................... 42 
 
Intervention Assessments .................................................................................... 42 
 
Efficacy Assessments .......................................................................................... 43 
8.2.1 
Serum Prostate-Specific Antigen ........................................................................ 43 
8.2.2 
Tumour Imaging ................................................................................................. 43 
8.2.3 
Assessment of Progression to Metastatic Disease Based on PCWG3 Criteria ... 44 
 
Exploratory Assessments .................................................................................... 44 
8.3.1 
Cellular Immune Response ................................................................................. 44 

 
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8.3.2 
Biomarkers .......................................................................................................... 45 
8.3.3 
Serum PSA-binding and anti-antigen Antibodies ............................................... 45 
8.3.4 
PSMA scan.......................................................................................................... 45 
 
Safety Assessments ............................................................................................. 45 
8.4.1 
Vital Signs ........................................................................................................... 45 
8.4.2 
Physical Examinations ........................................................................................ 46 
8.4.3 
Clinical Laboratory Assessments ........................................................................ 46 
8.4.4 
Electrocardiograms ............................................................................................. 47 
8.4.5 
Echocardiogram .................................................................................................. 47 
8.4.6 
Pregnancy ............................................................................................................ 47 
8.4.7 
Other Safety Assessments ................................................................................... 47 
9 
Adverse Events, Serious Adverse Events, Adverse Events of Special Interest and Other 
Safety Reporting .................................................................................................................. 48 
 
Time Period and Frequency for Collecting AE, SAE and AESI Information .... 48 
 
Follow-up of AEs and SAEs ............................................................................... 49 
 
Regulatory Reporting Requirements for SAEs ................................................... 49 
 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying 
as AEs or SAEs ................................................................................................... 49 
 
Adverse Events of Special Interest ..................................................................... 49 
10 
Pharmacokinetics ................................................................................................................. 50 
11 
Statistical Considerations .................................................................................................... 50 
 
Statistical Objectives ........................................................................................... 50 
11.1.1 
Multiplicity Adjustment ...................................................................................... 50 
11.1.2 
Analysis sets........................................................................................................ 50 
 
Statistical Analyses ............................................................................................. 51 
11.2.1 
General Considerations ....................................................................................... 51 
11.2.2 
Primary Endpoint Analysis ................................................................................. 51 
11.2.3 
Secondary Endpoint Analyses ............................................................................ 52 
11.2.4 
Exploratory Endpoint Analyses .......................................................................... 53 
11.2.5 
Other Analyses .................................................................................................... 53 
 
Interim Analysis .................................................................................................. 54 

 
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Sample Size Determination ................................................................................. 54 
12 
References ........................................................................................................................... 56 
 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations .............. 58 
 
Appendix 2: Clinical Laboratory Tests – Analytes and Laboratory Locations .. 62 
 
Appendix 3: AEs, AESIs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting .............................................. 63 
 
Appendix 4: Contraceptive and Barrier Guidance .............................................. 69 
 
Appendix 5: Abbreviations and Definitions ....................................................... 70 
 
Appendix 6: Changes made in Protocol Amendment ......................................... 72 
 
LIST OF TABLES 
Table 1 
Schedule of Assessments during the Screening and Intervention Periods .............. 15 
Table 2 
Schedule of Assessments during the Follow-up Periods ......................................... 19 
Table 3 
Summary of Potential Risks for VTP-850 Administration ..................................... 23 
Table 4 
Interventions Administered ..................................................................................... 37 
Table 5 
Phase 1 Trial Cohorts .............................................................................................. 38 
Table 6 
Confidence Intervals for True Serum PSA Response Rate Based on Observed 
Response Rate (n=125) ........................................................................................... 55 
Table 7 
Protocol-Required Laboratory Safety Tests ............................................................ 62 
Table 8 
Severity Grading of Adverse Events not listed in CTCAE ..................................... 65 
 
LIST OF FIGURES 
Figure 1 Trial Schematic ........................................................................................................ 14 
 
 

 
 
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1 
PROTOCOL SUMMARY 
 
Synopsis 
Protocol Number: 
PCA001 
Sponsor: 
Barinthus Biotherapeutics (UK) Ltd. 
Protocol Title: 
A Phase 1/Phase 2 Trial to Evaluate Safety, Immunogenicity and PSA Response of VTP-
850 Prostate Cancer Immunotherapeutic in Men with Biochemical Recurrence after 
Definitive Local Therapy for Prostate Cancer 
Short Title: 
Prime-boost Immunotherapeutic Trial in Men with Biochemical Recurrence after 
Definitive Local Therapy for Prostate Cancer 
Trial Centres: 
Up to 30 centres worldwide 
Objectives and 
Endpoints 
Primary Objective  
Primary Endpoints  
To evaluate the safety of VTP-850 
prime-boost regimens, with the booster 
dose administered either intramuscularly 
(IM) or intravenously (IV), and establish 
a recommended Phase 2 regimen (RP2R) 
• Number and proportion of participants 
with 
adverse 
events 
(AEs), 
treatment--related AEs, ≥Grade 3 AEs, 
≥Grade 3 treatment-related AEs, 
serious adverse events, and treatment-
related serious adverse events 
• Number and proportion of participants 
with clinically significant laboratory 
values 
• Change from baseline for laboratory 
tests and vital sign measurements at 
each time point of collection 
Secondary Objectives  
Secondary Endpoints  
To evaluate the prostate-specific antigen 
(PSA) response rate to VTP-850  
• Percentage of participants with ≥50% 
reduction in serum PSA compared to 
baseline at any time, based on two 
consecutive measurements, at least 
2 weeks apart 
To evaluate the durable PSA response 
rate to VTP-850 
• Percentage 
of 
participants 
with 
confirmed PSA response compared to 
baseline 
without 
having 
PSA 
progression on or before Month 8.  
To evaluate the duration of PSA response 
to 
VTP-850 
(for 
the 
subset 
of 
participants with PSA response) 
• Duration of PSA response (for the 
subset of participants with PSA 
response), defined as time from date of 
first dose of VTP-850 to the date of 
PSA progression (i.e., an increase of 
≥25% and an absolute increase of 
0.2 ng/mL or more from nadir) 
 
 
 

 
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To assess the Metastasis-free Survival 
(MFS) and Time to Metastases (TTM) of 
the subset of participants with PSA 
response 
• MFS is defined as the time from date of 
first dose of VTP-850 until metastatic 
disease 
by 
conventional 
imaging 
(computed tomography [CT]/magnetic 
resonance 
imaging 
[MRI] 
and/or 
technetium-99 bone scan) or death 
from any cause, whichever occurs first 
• TTM is defined as the time from date 
of first dose of VTP-850 until 
metastatic disease by conventional 
imaging 
(CT/MRI 
and 
or 
technetium-99 bone scan) 
Note that MFS and TTM events do not 
include 
local 
progression 
events, 
e.g., progression in pelvic lymph nodes 
below the aortic bifurcation. 
To assess the time to start of androgen 
deprivation therapy (ADT) for the 
participants with PSA response 
• Time from date of first dose of 
VTP-850 to the earliest of the start of 
ADT or the date when criteria to start 
ADT are met 
Exploratory Objectives 
Exploratory Endpoints 
To 
characterise 
immunogenicity 
(including 
antigen-specific 
T 
cell 
magnitude, phenotype and functionality 
associated with each regimen)  
CD4+ and CD8+ T cell response to the 
VTP-850 antigens in the peripheral 
blood as measured by multi-parameter 
flow cytometry and enzyme linked 
immunospot assays 
• Other immune responses to VTP-850 
To explore association of PSA response 
with biomarkers 
Microsatellite instability-high (MSI-H) 
status, BReast CAncer gene (BRCA) 
mutations 
(and 
other 
molecular 
markers 
Expression level of the VTP-850 antigens 
(PSA, 
prostatic 
acid 
phosphatase 
[PAP], six-transmembrane epithelial 
antigen of prostate 1 [STEAP1], 5T4) 
in historic tumour samples 
• Circulating tumour DNA 
• Serum PSA-binding antibodies 
To look for evidence of resolution of 
lesions on prostate-specific membrane 
antigen 
(PSMA) 
scan 
after 
administration 
of 
VTP-850 
(if 
documented at baseline), and association 
of resolution of such lesions with PSA 
response in the subset of participants 
who have lesions on baseline PSMA scan 
and who have a PSA response on trial 
• PSMA scans (optional)  

 
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To assess the MFS and TTM of all 
participants 
• MFS is defined as the time from date of 
first dose of VTP-850 until metastatic 
disease 
by 
conventional 
imaging 
(CT/MRI and/or technetium-99 bone 
scan) or death from any cause, 
whichever occurs first 
• TTM is defined as the time from date of 
first dose of VTP-850 until metastatic 
disease 
by 
conventional 
imaging 
(CT/MRI and/or technetium-99 bone 
scan)  
Note that MFS and TTM events do not 
include local progression events, e.g., 
progression in pelvic lymph nodes below 
the aortic bifurcation 
Trial Design: 
This is a multicentre, Phase 1/2, open-label clinical trial of the VTP-850 prime-boost 
immunotherapeutic in men with biochemical recurrence after definitive local therapy for 
prostate cancer. 
Participants in all cohorts will receive the ChAdOx1-PCAQ component on Day 1 
(prime) and the MVA-PCAQ component on Days 29 and 57 (boosts; Intervention 
Period). Participants will be followed until the Month 6 Visit or start of new therapy such 
as ADT or until development of unequivocal metastatic prostate cancer (Short-term 
Follow-up Period). Participants who have a PSA response will be followed for an 
additional 18 months, up to 24 months from first dose, or until start of new therapy such 
as ADT or development of unequivocal metastatic prostate cancer (Long-term Follow-
up Period). . In the event that a participant experiences a confirmed PSA response but 
subsequently experiences PSA progression more than 2 months after their final dose of 
VTP-850, an additional dose of MVA-PCAQ may be offered to the participant. 
Phase 1 will determine the RP2R (dose level of both ChAdOx1-PCAQ and 
MVA-PCAQ, and route of administration of MVA-PCAQ) that will be used in Phase 2 
and will follow a 3+3 design. 
The first 3 participants will be enrolled in Cohort 1. Enrolment of the first 3 participants 
in each cohort will be staggered by at least 9 days. The medical monitor will review the 
safety data for the previous participant, at least 7 days after the prime dose and after the 
first booster dose of VTP-850, before the corresponding dose is administered to the next 
participant. The safety review will include data from at least 7 days after each 
ChAdOx1-PCAQ prime dose; at least 7 days after the first booster MVA-PCAQ dose if 
administered IM; and at least 14 days after the first booster dose of MVA-PCAQ if 
administered IV. If 1 or more of the 3 participants has a dose limiting toxicity (DLT), 3 
additional participants may be enrolled into Cohort 1. If there is no DLT after the first 
dose of VTP-850 in the first 3 participants, 3 participants will be enrolled into each of 
Cohorts 2 and 3 concurrently, with the first participants in Cohorts 2 and 3 staggered by 
at least 9 days to allow for medical review. If DLT is not seen in more than 1 participant 
in Cohort 2 after the first dose of VTP-850, then an additional 3 participants will be 
enrolled into Cohort 2. Safety data for the DLT period following each booster dose will 
be assessed by the medical monitor prior to the corresponding booster dose being 
administered to additional participants. If DLT is not seen after the first dose of VTP-
850 in more than 1 participant in Cohort 3 then an additional 3 participants will be 
enrolled into Cohort 3. Safety data for the DLT period following each booster dose will 
be assessed by the medical monitor prior to the corresponding booster dose being 
administered to additional participants. A total of 6 participants in each of Cohorts 2 and 
3 will be dosed with MVA-PCAQ on Day 29 and Day 57. Therefore, participants who 
withdraw before dosing, before completion of dosing or who have dose delays will be 

 
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replaced (unless the reason for not completing dosing per protocol is related to a  
stopping rule criteria being met) If the safety of one or more cohorts is acceptable after 
all participants have been followed through the DLT period after the first booster dose 
of VTP-850, then a Phase 2 dosing regimen will be selected based on safety data, and 
recruitment to Phase 2 will be opened. 
Phase 2 of the trial will consist of 2 sequential stages. 
In Stage 1 of Phase 2, 19 additional participants will be enrolled at the chosen Phase 2 
regimen. If 4 or more of the 25 participants at the RP2R (out of the 19 Phase 2 
participants and the 6 Phase 1 participants who received the same dose regimen 
according to the dosing schedule) have a PSA response, Stage 2 will be opened to 
enrolment of up to 100 additional participants. If 3 or fewer of the 25 participants have 
a PSA response in Stage 1, no further participants will be enrolled. PSA response is 
defined as ≥50% reduction in serum PSA compared to baseline at any time, measured at 
two consecutive timepoints, at least 2 weeks apart.  
The Safety Monitoring Committee (SMC) will make a recommendation whether 1) to 
enrol each cohort in Phase 1, 2) about the choice of RP2R after reviewing available 
safety data and whether to open enrolment in Phase 2 and 3) to open enrolment in Phase 2 
Stage 2 after reviewing available safety and efficacy data after at least 4 participants have 
exhibited a PSA response.  
Phase 1: Dose/Regimen Finding Phase 
Phase 2: Main Phase 
 
 
 
 
 
 
Abbreviations: IM=intramuscular, IV=intravenous, *n=number of participants who have received their 
scheduled doses of MVA-PCAQ on Day 29 and Day 57, 
Trial Intervention: 
VTP-850 consists of 2 components: ChAdOx1-PCAQ and MVA-PCAQ. Participants in 
all cohorts will receive the ChAdOx1-PCAQ component on Day 1 and the MVA-PCAQ 
component on Days 29 and 57. 
In the event that a participant experiences a confirmed PSA response but subsequently 
experiences PSA progression more than 2 months after their final dose of VTP-850, an 
additional dose of MVA-PCAQ may be offered to the participant. 
Dose Levels 
Cohort 
 
Number of 
participants 
Trial Intervention: VTP-850 
ChAdOx1-PCAQ 
Day 1 
MVA-PCAQ 
Days 29 and 57 
1 
3-6 
5×109 vp IM 
5×107 pfu IM 
2 
6 
2.5×1010 vp IM 
2×108 pfu IM 
3 
6 
2.5×1010 vp IM 
2×107 pfu IV 
Abbreviations: IM=intramuscular, IV=intravenous, pfu=plaque forming units, vp=viral particles 
Duration of Trial: 
Maximum duration for each participant: Up to 24 months after first dose of VTP-850.  
Duration of whole trial: Approximately 42 months (18 months recruitment + 24 months 
follow-up). 
Participant 
Numbers: 
A total of approximately 25 participants will be enrolled in Phase 1 (including 
replacement participants so that 6 participants in each of Cohorts 2 and 3 have received 
MVA-PCAQ at Days 29 and 57); 19 participants will be enrolled in Stage 1 of Phase 2, 
and 100 participants will be enrolled in Stage 2 of Phase 2.  
Stage 2 
(n=100) 
Cohort 2 (IM/IM) 
Full Dose 
(n=6)* 
Cohort 1 (IM/IM) 
Low Dose 
(n=3-6) 
Cohort 3 (IM/IV) Full 
Dose 
(n=6)* 
Stage 1 
(n=25) 
(Includes 6 from 
Phase 1)

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Inclusion Criteria: 
Age 
1. Males aged 18 years and above at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Histologically or cytologically confirmed adenocarcinoma of the prostate.
3. Has undergone primary therapy for prostate cancer (radical prostatectomy and/or 
definitive external beam radiation and/or brachytherapy). Salvage external radiation 
therapy (XRT) following radical prostatectomy >6 months prior to Day 1 is allowed.
4. No further local therapy to prostate or systemic therapy for prostate cancer and no 
metastasis-directed therapy for PSA-positron emission tomography (PET) positive 
lesions planned within 4 months after the first dose of VTP-850.
5. Serum testosterone >175 ng/dL.
6. Nonmetastatic (M0) disease and no evidence of prostatic bed recurrence verified by 
whole body bone scintigraphy and either CT or MRI. Note that a positive 
PSMA-PET does not exclude the participant if the conventional scans are negative.
7. Serum PSA of >0.3 ng/mL for participants with prior radical prostatectomy (with or 
without salvage radiotherapy), or serum PSA of 2 ng/mL above nadir for participants 
with prior external beam radiation or brachytherapy.
8. PSA doubling time ≤12 months.
9. Not planning to start ADT for at least 4 months after Day 1.
10.  Eastern Cooperative Oncology Group (ECOG) Score 0 or 1.
11.  Baseline laboratory parameters must meet the following criteria:
•
Haemoglobin ≥110 g/Le
•
White cell count ≥2.0×109/L
•
Absolute neutrophil count ≥1.5×109/L
•
Lymphocytes ≥0.9×109/L
•
Platelets ≥100×109/L
•
Creatinine ≤1.5×upper limit of normal (ULN) OR calculated creatinine 
clearance ≥50 mL/min by the Cockcroft Gault formula
•
Total bilirubin ≤1.5×ULN, (total bilirubin >1.5×ULN is acceptable if total 
bilirubin is fractionated and direct bilirubin <35%)
•
Alanine aminotransferase ≤1.5×ULN
•
Aspartate aminotransferase ≤1.5×UL
•
Troponin T within normal range
•
HbA1c <7 %
Sex and Contraceptive/Barrier Requirements 
12. Agrees to the following during the trial and for at least 65 days after the last dose of
VTP-850:
•
Refrain from donating sperm
PLUS, either 
•
Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agree to remain
abstinent
OR 

 
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• 
Agrees to use a male condom when having sexual intercourse with a 
woman of childbearing potential, and should also be advised of the benefit 
for a female partner to use a highly effective method of contraception as a 
condom may break or leak. 
Other Inclusions 
13. Agrees to comply with all scheduled visits, VTP-850 administration plan, laboratory 
tests, lifestyle considerations and other trial procedures. 
Exclusion Criteria 
Cancer History 
1. Any other prior malignancy within the past 5 years except for basal cell or squamous 
epithelial carcinomas of the skin that have been resected with no evidence of 
metastatic disease for 3 years. 
Medical Conditions 
2. Unstable medical condition, drug or alcohol abuse, or medical or psychiatric 
condition that in the opinion of the investigator would affect the safety of the 
participant or the evaluation of the data or interfere with adherence to the trial 
requirements.  
3. Significant history of or current cardiovascular, respiratory, renal, gastrointestinal, 
endocrinological, haematological or neurological disorders constituting a risk when 
taking the trial intervention or interfering with the interpretation of data; cardiac 
event or heart failure in the previous 6 months. 
4. Current or chronic history of liver disease. This includes but is not limited to: 
hepatitis virus infections, cirrhosis, drug- or alcohol-related liver disease, 
non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson’s 
disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing 
cholangitis or any other liver disease considered clinically significant by the 
investigator. (Note that history of hepatitis C infection, Gilbert’s syndrome or 
non-alcoholic fatty liver not associated with steatohepatitis are not exclusions.  In 
line with Exclusion Criterion 10, active hepatitis C infection is exclusionary.) 
5. Active autoimmune disease that has required systemic treatment in past 2 years with 
use of disease modifying agents, chronic corticosteroids (>14 days) or 
immunosuppressive drugs. Hormone replacement therapy (e.g., thyroxine, insulin or 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) 
is allowed. 
6. History of severe allergy to eggs or history of severe reaction to any previous 
vaccination that required medical attention. 
7. Medical history that could increase the participant’s risk of reaction to a vaccine, 
including but not limited to capillary leak syndrome, transverse myelitis, multiple 
sclerosis, Guillain Barré syndrome, significant thrombocytopenia, thrombosis with 
thrombocytopenia 
syndrome 
(also 
termed 
vaccine-induced 
thrombotic 
thrombocytopenia), heparin-induced thrombocytopenia, or hereditary angioedema, 
acquired angioedema or idiopathic angioedema. 
8. Any immunocompromised state, or history of solid organ or stem cell 
transplantation. 
9. Active infection requiring parenteral antibiotic therapy or causing fever (temperature 
≥38.0˚C) within 7 days prior to Day 1, or unexplained fever (temperature ≥38.0˚C) 
within 7 days prior to Day 1. 
10. Known history of infection with hepatitis B virus, or human immunodeficiency 
virus, or active hepatitis C virus infection (antibody and RNA positive). 

 
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Prior/Concomitant Therapy 
11. Received XRT following radical prostatectomy within 6 months prior to Day 1. 
12. Received ADT outside of the initial primary therapy 
13. Prior chemotherapy or immunotherapy (including vaccines or checkpoint inhibitors) 
or experimental agent or participation in a clinical trial for prostate cancer with the 
exception of those taking part as primary treatment option. 
14. Received a vaccine with adenovirus vector within 3 months prior to Day 1. 
15. Received any live vaccine within 30 days prior to Day 1, or planned vaccination to 
occur within 3 months after Day 1. 
16. Received any non-live/inactivated vaccine within 14 days of Day 1 or planned 
non-live vaccination to occur within 10 weeks after Day 1. 
17. Administration of immunoglobulins and/or any blood products within 28 days prior 
to Day 1. 
18. Condition 
requiring 
systemic 
treatment 
with 
corticosteroids 
or 
other 
immunosuppressive medications within 14 days of first dose of VTP-850. Note that 
adrenal replacement doses are permitted. Inhaled and topical corticosteroids are 
allowed. 
19. Received an investigational product or investigational surgical procedure in the 3 
months prior to Day 1 or planned use during the trial period, or participation at any 
time in clinical trial for prostate cancer with exception of those taking part as primary 
treatment. 
Cardiovascular Risk Profile 
20. Any significant cardiovascular conditions per the investigator within 6 months 
before study entry including but not limited to: myocardial infarction, stroke, New 
York Heart Association class III or IV heart failure, thromboembolic events, major 
cardiovascular or cerebrovascular procedures, history of cardiac valvular disease or 
other structural heart disease or any other condition that in the investigator's opinion 
puts the participant at unacceptable risk to enter the study. 
21. Participant with QT interval corrected for heart rate (QTc) determined using 
Fridericia's formula (QTcF; QTcF = QT/[R-R interval {RR}^0.33]) > 470 msec and 
any other ECG findings deemed clinically significant at screening 
22. Uncontrolled hypertension that, in the opinion of the Investigator, puts participant at 
increased risk of a cardiovascular event at the time of screening. 
23. Uncontrolled dyslipidemia that, in the opinion of the Investigator, puts participant at 
increased risk of cardiovascular event at the time of screening. 

 
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Schema 
Figure 1 
Trial Schematic 
Phase 1: Dose/Regimen Finding Phase 
Phase 2: Main Phase 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: IM=intramuscular, IV=intravenous, *n=number of participants who have received their scheduled doses of MVA-PCAQ on Day 29 and Day 57, 
pfu=plaque forming units, vp=viral particles 
 
 
Stage 2 
(n=100) 
Cohort 2 (IM/IM) Full Dose 
(n=6)* 
ChAdOx1-PCAQ 2.5×1010 vp 
MVA-PCAQ 2×108 pfu 
Cohort 1 (IM/IM) Low Dose 
(n=3-6) 
ChAdOx1-PCAQ 5×109 vp 
MVA-PCAQ 5×107 pfu 
Cohort 3 (IM/IV) Full Dose 
(n=6)* 
ChAdOx1-PCAQ 2.5×1010 vp 
MVA-PCAQ 2×107 pfu 
Stage 1 
(n=25) 
(Includes 6 from Phase 1) 

 
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Schedule of Assessments 
Table 1 
Schedule of Assessments during the Screening and Intervention Periods 
Visit/Call 
Screening 
Period 
(42 d)a 
Intervention Period (Days) 
Day 1 
Dosing 
Visit 
Day 2 
Telephone 
Call 
Day 8 
Telephone 
Call 
Day 15 
Clinic 
Visit 
Day 29 
Dosing 
Visit 
Day 30 
Telephone 
Call 
Day 36 
Clinic 
Visit 
Day 43 
Clinic 
Visit 
Day 57 
Dosing 
Visit k 
Day 58 
Telephone 
Call k 
Day 64 
Clinic 
Visit k 
Day 71 
Clinic 
Visit k 
Day 91 
Clinic 
Visit 
Windowb 
 
 
1-2d 
post-dose 
±1d 
±2d 
±2d 
Up to 2d 
post-dose 
±2d 
±2d 
±2d 
Up to 2 d 
post-dose 
±2d 
±2d 
±2d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline/eligibility variables 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion 
and 
exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full 
physical 
examination 
including height and weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and disease history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Historic 
tumour 
sample 
collectione 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory eligibility and 
safety 
tests 
and 
investigations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECGc 
X 
X (pre-
dose) 
 
 
X 
X (pre-
dose) 
 
 
X 
X (pre-
dose) 
 
 
X 
X 
Echocardiogramd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Visit/Call 
Screening 
Period 
(42 d)a 
Intervention Period (Days) 
Day 1 
Dosing 
Visit 
Day 2 
Telephone 
Call 
Day 8 
Telephone 
Call 
Day 15 
Clinic 
Visit 
Day 29 
Dosing 
Visit 
Day 30 
Telephone 
Call 
Day 36 
Clinic 
Visit 
Day 43 
Clinic 
Visit 
Day 57 
Dosing 
Visit k 
Day 58 
Telephone 
Call k 
Day 64 
Clinic 
Visit k 
Day 71 
Clinic 
Visit k 
Day 91 
Clinic 
Visit 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Haematology  
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Biochemistry 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Liver function tests 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Troponin Tc,f 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
CRP 
X 
X 
 
 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
Serum testosterone 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intervention 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrolment /confirmation that 
eligibility requirements still 
met prior to dosing 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
VTP-850 dose 
 
ChAd 
 
 
 
MVA 
 
 
 
MVA 
 
 
 
 
Post-dose observation 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
Other safety assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptom-directed physical 
examination 
 
X 
 
 
X 
X 
 
 
X 
X 
 
 
X 
X 
Vital signs 
X 
Xg 
 
 
X 
Xg 
 
 
X 
Xg 
 
 
X 
X 
Medical occurrences 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events  
 
========================================================================================= 
Serious adverse 
events/AESIsc 
Xh 
========================================================================================= 

 
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Visit/Call 
Screening 
Period 
(42 d)a 
Intervention Period (Days) 
Day 1 
Dosing 
Visit 
Day 2 
Telephone 
Call 
Day 8 
Telephone 
Call 
Day 15 
Clinic 
Visit 
Day 29 
Dosing 
Visit 
Day 30 
Telephone 
Call 
Day 36 
Clinic 
Visit 
Day 43 
Clinic 
Visit 
Day 57 
Dosing 
Visit k 
Day 58 
Telephone 
Call k 
Day 64 
Clinic 
Visit k 
Day 71 
Clinic 
Visit k 
Day 91 
Clinic 
Visit 
Prior and concomitant 
medications 
================================================================================================ 
Efficacy assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum PSA 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
Radiological assessment 
Xi 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for PBMC assessmentj 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
Blood for ctDNA assessment 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Blood for PSA-binding 
antibody/anti-vector 
antibody/anti-antigen 
antibody assessment 
 
X 
 
 
X 
X 
 
 
X 
X 
 
 
X 
X 
Abbreviations: AESI – Adverse Event of Special Interest, C3=Cohort 3, ChAd=ChAdOx1-PCAQ, CRP=C-reactive protein, CT=computed tomography, ctDNA=circulating 
tumour DNA, d=day(s), ECG=electrocardiogram, ECOG=Eastern Cooperative Oncology Group, MVA=MVA-PCAQ, MRI=magnetic resonance imaging, 
PBMC=peripheral blood mononuclear cells, PET=positron emission tomography, PSA=prostate-specific antigen, SAE=serious adverse event 
a If the screening period is longer than 42 days, the participant must be reconsented. Consult with the Medical Monitor for which assessments should be repeated. 
b Windows during the intervention period are calculated from the date of the previous VTP-850 dose. 
c If a cardiac event is reported, blood should be taken for an additional assessment of troponin T and the participant should undergo an additional ECG and 
echocardiogram at the earliest opportunity. 
d Historic echocardiogram may be used if performed within 3 months of Day 1. 
e May be retrieved at any time during the intervention period. 
f If troponin T test result is abnormal, a re-test on the following day is required. 
g Pre-dose and approximately 30 min post-dose. 
h During the screening period, only SAEs that are causally related to a screening procedure should be collected. 
I Historic CT/MRI/PET scans and bone scans may be used if performed within 3 months of Day 1. If no historic scan is available, a bone scan and a CT or MRI 
will be performed. 

 
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j Only required at sites qualified by Barinthus Biotherapeutics to perform PBMC isolation/processing. 
k Optional schedule to be repeated for participants receiving a third dose of MVA-PCAQ after initial PSA response followed by progression. Schedule to be 
repeated for participants whose 2nd dose of MVA was delayed. 

 
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Table 2 
Schedule of Assessments during the Follow-up Periods 
Clinic Visit 
Short-term Follow-up Period 
Long-term Follow-up Period 
Month 4 
(Day 120)  
Month 5 
(Day 150)   
Month 6 
/EOTa 
(Day 180) 
Months 
7/9/10/11/14/ 
16/20/22 
(Days 210/270 
/300/330/420/ 
480/600/660) 
Month 8 
(Day 240) 
Month 12 
(Day 360) 
Month 18 
(Day 540) 
Month 24 
(Day 720)/ 
EOT 
Windowb 
±7d 
±7d 
±7d 
±7d 
±7d 
±7d 
±7d 
±7d 
Symptom-directed physical 
examination 
 
 
X 
 
 
 
 
X 
12-lead ECGc 
 
 
X 
 
 
 
 
 
Vital signs 
 
 
X 
 
 
 
 
X 
Adverse events  
============================ 
 
 
 
 
 
Serious adverse events/ AESIs 
=================================================================================== 
Prior and concomitant 
medications 
=================================================================================== 
Laboratory safety tests 
Haematology  
 
 
X 
 
 
 
 
 
Biochemistry 
 
 
X 
 
 
 
 
 
Liver function tests 
 
 
X 
 
 
 
 
 
Troponin Tc,d 
 
 
X 
 
 
 
 
 
Efficacy assessments 
Serum PSA 
X 
X 
X 
X 
X 
X 
X 
X 
Radiological assessment 
 
 
X 
(+/- 14 days) 
 
 
X 
(+/- 14 days) 
X 
(+/- 14 days) 
X 
(+/- 14 days) 
PSMA scan (optional)e 
===================================================================================  

 
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Clinic Visit 
Short-term Follow-up Period 
Long-term Follow-up Period 
Month 4 
(Day 120)  
Month 5 
(Day 150)   
Month 6 
/EOTa 
(Day 180) 
Months 
7/9/10/11/14/ 
16/20/22 
(Days 210/270 
/300/330/420/ 
480/600/660) 
Month 8 
(Day 240) 
Month 12 
(Day 360) 
Month 18 
(Day 540) 
Month 24 
(Day 720)/ 
EOT 
Immunogenicity assessments 
 
 
 
 
 
 
 
 
Blood for PBMC assessmentf 
 
 
 
 
X 
X 
 
 
Blood for anti-antigen antibody 
assessment 
 
 
 
 
X 
X 
 
 
Abbreviations: AESIs- Adverse Events of Special Interest, d=days, EOT=End of Trial, PBMC=peripheral blood mononuclear cells, PSA=prostate-specific antigen, 
PSMA=prostate-specific membrane antigen 
a Participants will only have 1 EOT visit at either Months 6 or 24 or earlier in the event of initiation of new therapy (such as ADT) or development of unequivocal 
metastatic prostate cancer. Participants with no PSA response in the first 6 months will not enter the Long-Term Follow-up Period. Participants with a PSA response 
through Month 6 will enter the Long-term Follow-up Period. 
b Visits during the Follow-up Periods are from Day 1. Windows are relative to the target date of the visit. 
c If a cardiac event is reported, blood should be taken for an additional assessment of troponin T and the participant should undergo an additional ECG and 
echocardiogram at the earliest opportunity 
d If troponin T test result is abnormal, a re-test on the following day is required. 
e PSMA scan can be performed at any time for participants who had a positive PSMA scan prior to screening and where a 50% reduction from baseline in PSA is 
observed. 
f Only required at sites qualified by Barinthus Biotherapeutics to perform PBMC isolation/processing.  

 
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2 
INTRODUCTION 
 
Trial Rationale 
VTP-850 is a prime-boost immunotherapeutic regimen consisting of 2 viral vectored 
components, ChAdOx1-PCAQ and MVA-PCAQ. ChAdOx1-PCAQ, the prime dose, consists of 
a recombinant nonreplicating chimpanzee adenovirus Oxford 1 (ChAdOx1) vector encoding 
4 prostate cancer antigens: prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), 
six-transmembrane epithelial antigen of prostate 1 (STEAP1), and 5T4, an oncofoetal antigen. 
MVA-PCAQ, the component used for the booster doses, consists of a replication-deficient 
recombinant Modified Vaccinia virus Ankara (MVA) vector encoding the same prostate cancer 
antigens as ChAdOx1-PCAQ. 
ChAdOx1 and MVA have been incorporated as vectors in different prophylactic vaccines and 
immunotherapeutics for infectious diseases and cancers. They have both demonstrated 
immunogenicity in nonclinical and clinical studies for these various indications. 
VTP-800 was an earlier immunotherapeutic for prostate cancer that used the same 
ChAdOx1/MVA heterologous prime/boost platform as VTP-850 but included only one antigen, 
5T4. VTP-800 was studied in prostate cancer patients in 2 trials at the University of Oxford. 
The VANCE trial in newly diagnosed prostate cancer patients demonstrated immunogenicity and 
safety of VTP-800. 5T4-specific T cell responses were seen in 25 of the 39 patients (64%), and 
the median peak for responders was 198 spot forming cells/million.[1] In the ADVANCE trial in 
metastatic castration-resistant prostate cancer, VTP-800 was administered with nivolumab, and 
5 of 23 patients (22%) had a >50% reduction in PSA level at any time point compared to 
baseline. Three of the responders had measurable lesions at baseline and also had partial 
response according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. However, 
3 of the PSA responses were transient. 
Barinthus Biotherapeutics (formerly known as Vaccitech) designed VTP-850 to induce a broader 
immune response than VTP-800 by encoding multiple antigens to reduce the ability of cancer 
cells to evade the immune response by mutating or losing expression of any one antigen. 
Trial PCA001 is the first-in-human trial of VTP-850. The aim of this trial is to evaluate the 
safety, immunogenicity, and the rate and duration of PSA response of VTP-850 in patients with 
biochemical recurrence after definitive local therapy for prostate cancer. The efficacy of 
VTP-850 will be assessed by the PSA response rate.  In addition, the quality of the responses 
will be characterised by determining the duration of PSA response and by following the 
responders to establish whether the responders require new treatment for prostate cancer or 
develop metastases during long term follow-up. During the Dose/Regimen Finding Phase, 
different dose levels of each component will be evaluated, with the MVA-PCAQ component 
evaluated in different cohorts as either an intramuscular (IM) injection or an intravenous (IV) 
infusion. 

 
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Background 
Prostate cancer is the second most frequent cancer diagnosis in men and the fifth leading cause 
of cancer-related deaths in men worldwide.[2] In 2018, approximately 1.3 million new cases 
were diagnosed, and approximately 360,000 deaths occurred. The incidence and mortality of 
prostate cancer increase with age, with the average age of diagnosis being 66 years.[2] 
Furthermore, the incidence of prostate cancer is expected to increase due to longer life 
expectancy and lifestyle factors. The rates are highest in North America, Australia, and northern 
and central Europe, and lowest in south-eastern and south-central Asia and northern Africa.[2] 
The serum concentration of PSA is usually elevated in men with prostate cancer and is used to 
monitor the progression of prostate cancer in men who have already been diagnosed with the 
disease. About 90% of patients with prostate cancer have localised or regional disease at the time 
of diagnosis. Localised or regional prostate cancer can be treated with radiation or surgical 
removal of the prostate. These localised therapies can be curative, but the cancer recurs in 
approximately 20% to 30% of patients. Patients with localised prostate cancer may also receive 
androgen deprivation therapies (ADTs), as androgens stimulate the growth of prostate cancer 
cells. Patients with recurrent disease are typically offered ADT when they present with 
symptomatic local disease progression, proven metastases or a PSA doubling time of less than 
3 months.[3] If a patient has evidence that their cancer is progressing despite ADT, such as 
increasing PSA in their blood or new bone metastases, it signifies that their disease is 
castration-resistant.[4] 
Once prostate cancer becomes metastatic, it is considered incurable. Current treatment options 
for metastatic prostate cancer include androgen receptor inhibitors, such as enzalutamide and 
abiraterone; chemotherapy including docetaxel and cabazitaxel; a radioactive isotope 
radium-223; lutetium vipivotide tetraxetan, a radiopharmaceutical, and sipuleucel-T, a 
patient-specific immunotherapeutic. All of these treatments have been shown to improve 
survival, but once the cancer is castration-resistant, the median overall survival is less than 
3 years. 
Recent Phase 3 clinical studies have shown that drugs such as enzalutamide, apalutamide, 
abiraterone and docetaxel can provide a survival advantage when used earlier in a patient’s 
course of treatment, but the optimal sequence for the different treatment types has yet to be 
determined.  
Patients with prostate cancer have few options once metastatic disease is evident. Targeting the 
disease earlier in its development may be an effective strategy to prevent or delay the 
development of metastases and may allow patients to delay or avoid ADT and other therapies. 
VTP-850 is designed as a potentially low-toxicity immunotherapeutic intervention to treat 
prostate cancer, prior to metastases forming, while the disease is still considered castration 
sensitive, but with rising PSA values. 
 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of VTP-850 may be found in the Investigator’s Brochure (IB). 

 
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2.3.1 Risk Assessment 
A summary of potential risks for VTP-850 administration is included in Table 3. 
Table 3 
Summary of Potential Risks for VTP-850 Administration 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Trial Intervention (VTP-850) 
A potential signal of cardiac risk 
has been identified and assessed 
following administration of VTP-
850 in the trial population  
In the first 14 participants 
treated, a potential cardiac-
related death has been reported 
together with non-serious 
adverse events of dyspnoea, and 
dyspnoea exertional and atrial 
fibrillation in two further 
participants. These events have 
a possible temporal relationship 
to trial intervention, occurring 
within a similar timeframe after 
the first MVA-PCAQ boost. 
Participants with a history of 
cardiac events that put them at 
risk will be excluded from the 
trial.  In addition, cardiac 
monitoring (ECG and laboratory 
blood tests) will be performed at 
pre-defined timepoints during the 
first 6 months of the trial and a 
baseline echocardiogram will be 
performed to exclude participants 
with any clinically significant 
abnormalities. 
Potential for local reactions 
(injection site redness, injection 
site swelling and injection site 
pain) and systemic reactions 
(including fever, chills, 
feverishness and headache) 
following IM administration.  
These are common reactions seen 
with other products that use the 
same viral vectors as are used in 
VTP-850. Further details are 
provided in the current IB. 
The investigator site will contact 
the participant one day after the 
administration of each component 
of VTP-850 7 days after the 
administration of 
ChAdOx1-PCAQ, and the 
participant will return to the clinic
7 days after each administration 
of MVA-PCAQ, at which times 
the trial staff will record AEs  
With any immunotherapeutic 
there is a rare risk of anaphylaxis 
which can be fatal. 
- 
Participants will be dosed in a 
clinical area where appropriate 
drugs and medical equipment to 
treat acute anaphylactic reactions 
are immediately available for the 
management of such adverse 
reactions in the immediate 
post-administration period. 
Participants are observed in the 
clinic for at least 30 min 
post-dose.  
Participants with history of 
anaphylaxis to previous 
vaccination are excluded. 

 
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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Potential risk of elevated liver 
function tests following IV 
MVA-PCAQ. 
Transient laboratory 
abnormalities including increases 
in liver function tests following 
IV dosing were observed in 
clinical studies with an MVA-
vectored vaccine for malaria. 
These abnormalities were without 
clinical symptoms or signs and 
returned toward baseline values 
over time. The clinical 
significance of these observations 
is unknown. 
Safety labs at 7 and 14 days after 
each IV administration of 
MVA-PCAQ. 
The first 3 participants who 
receive IV MVA-PCAQ will be 
staggered so that the second and 
third participants do not receive 
MVA-PCAQ until the laboratory 
results following the previous 
participant’s initial MVA-PCAQ 
dosing have been assessed. 
Unknown AEs and laboratory 
abnormalities with a novel 
immunotherapeutic. 
This trial is the first time VTP-
850 will be administered to 
humans. 
Routine safety laboratory testing 
(including haematology, 
chemistry, liver function tests) 
and clinical assessments will be 
obtained during the Intervention 
and Follow-up Periods to monitor 
for expected and unexpected AEs.
A Safety Monitoring Committee 
(SMC) will review safety data 
during the trial. 
Potential very rare adverse events 
that have occurred in people who 
have received a different 
ChAdOx1-vectored product. 
There have been very rare events 
of thrombosis with 
thrombocytopenia, Guillain Barré 
Syndrome, and capillary leak 
syndrome with the ChAdOx1-
vectored vaccine Vaxzevria, 
which is authorised in many parts 
of the world. It is not known if 
these are related to the ChAdOx1 
vector. Such events have not been 
detected with other ChAdOx1-
vectored products to date, and it 
is not known if they will occur 
with ChAdOx1-PCAQ. 
Participants with previous history 
of thrombosis with 
thrombocytopenia, Guillain Barré 
Syndrome, and capillary leak 
syndrome have been excluded 
from the trial because it is 
possible that they may be at 
higher risk. 
Trial Procedures 
Venipuncture will be performed 
during the trial. 
There is the risk of bleeding, 
bruising, haematoma formation 
and infection at the venipuncture 
site. 
Only appropriately qualified 
personnel would perform the 
blood draw. 

 
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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Bone scans and radiographic 
assessments will be performed 
during the trial. 
There is a low risk of allergic 
reaction to contrast material. 
Bone scans and CT scans involve 
exposure to small amounts of 
radiation. 
Only appropriately qualified 
personnel would perform 
radiographic procedures. 
Abbreviations: AE=adverse event, CT=computed tomography, IM=intramuscular, IV=intravenous 
2.3.2 Benefit Assessment 
Potential benefits to individual participants may include:  
Receipt of a potentially efficacious immunotherapeutic for prostate cancer. However, as this is an early 
development trial with no previous efficacy data, there may be no such benefit to trial participants. 
The participants will receive additional monitoring of their prostate cancer compared to the standard 
of care. 
• 
Contributing to research to help others. Participation in this trial may contribute to the 
development of a treatment for prostate cancer. 
2.3.3 Overall Benefit-Risk Conclusion 
Taking into account the measures taken to minimise risk to participants participating in this trial, 
the potential risks identified in association with VTP-850 are justified by the anticipated benefits 
that may be afforded to participants with prostate cancer.  
 
 

 
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3 
OBJECTIVES AND ENDPOINTS 
Primary Objective 
Primary Endpoints 
To evaluate the safety of VTP-850 prime-boost 
regimens, with the booster dose administered either 
IM or IV, and establish an RP2R  
• Number and proportion of participants with AEs, 
treatment-related AEs, ≥Grade 3 AEs, ≥Grade 3 
treatment-related AEs, serious adverse events, and 
treatment-related serious adverse events 
• Number and proportion of participants with clinically 
significant laboratory values  
• Change from baseline for laboratory tests and vital 
sign measurements at each time point of collection 
Secondary Objectives 
Secondary Endpoints 
To evaluate the PSA response rate to VTP-850  
• Percentage of participants with ≥50% reduction in 
serum PSA compared to baseline at any time, based on 
two consecutive measurements, at least 2 weeks apart 
To evaluate the durable PSA response rate to 
VTP-850 
• Percentage of participants with confirmed PSA 
response compared to baseline without having PSA 
progression on or before Month 8. 
To evaluate the duration of PSA response to 
VTP-850 (for the subset of participants with PSA 
response) 
• Duration of PSA response (for the subset of 
participants with PSA response), defined as time from 
date of first dose of VTP-850 to the date of PSA 
progression (i.e., an increase of ≥25% and an absolute 
increase of 0.2 ng/mL or more from nadir)  
To assess the Metastasis-free Survival (MFS) and 
Time to Metastases (TTM) of the subset of 
participants with PSA response 
• MFS is defined as the time from date of first dose of 
VTP-850 until metastatic disease by conventional 
imaging (CT/MRI and/or technetium-99 bone scan) or 
death from any cause, whichever occurs first 
• TTM is defined as the time from date of first dose of 
VTP-850 until metastatic disease by conventional 
imaging (CT/MRI and/or technetium-99 bone scan)  
Note that MFS and TTM events do not include local 
progression events, e.g., progression in pelvic lymph 
nodes below the aortic bifurcation.  
To assess the time to start of ADT for the participants 
with PSA response 
• Time from date of first dose of VTP-850 to the earliest 
of the start of ADT or the date when criteria to start 
ADT are met 
Exploratory Objectives 
Exploratory Endpoints 
To characterise immunogenicity (including antigen-
specific 
T 
cell 
magnitude, 
phenotype 
and 
functionality associated with each regimen) 
CD4+ and CD8+ T cell response to the VTP-850 antigens 
in 
the 
peripheral 
blood 
as 
measured 
by 
multi-parameter flow cytometry and enzyme linked 
immunospot assays 
• Other immune responses to VTP-850 

 
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To explore association of PSA response with 
biomarkers 
Microsatellite instability-high status (MSI-H), Breast 
Cancer gene (BRCA) mutations and other molecular 
markers 
Expression level of the VTP-850 antigens (PSA, prostatic 
acid phosphatase [PAP], six-transmembrane epithelial 
antigen of prostate 1 [STEAP1], 5T4) in historic 
tumour samples 
• Circulating tumour DNA 
• Serum PSA-binding antibodies 
To look for evidence of resolution of lesions on 
PSMA scan after administration of VTP-850 (if 
documented at baseline), and association of 
resolution of such lesions with PSA response in the 
subset of participants with baseline PSMA scan who 
have a PSA response on trial 
• PSMA scans (optional)  
To assess the MFS and TTM of all participants 
• MFS is defined as the time from date of first dose of 
VTP-850 until metastatic disease by conventional 
imaging (CT/MRI and/or technetium-99 bone scan) or 
death from any cause, whichever occurs first 
• TTM is defined as the time from date of first dose of 
VTP-850 until metastatic disease by conventional 
imaging (CT/MRI and/or technetium-99 bone scan)  
Note that MFS and TTM events do not include local 
progression events, e.g., progression in pelvic lymph 
nodes below the aortic bifurcation 
Abbreviations: ADT=androgen deprivation therapy, CT=computed tomography, IM=intramuscular, 
IV=intravenous, MFS=Metastasis-free Survival, MRI=magnetic resonance imaging, PSA= prostate-specific 
antigen, PSMA=prostate-specific membrane antigen, RP2R=recommended Phase 2 regimen, TTM=Time to 
Metastases 
4 
TRIAL DESIGN 
 
Overall Trial Design 
This is a multicentre, Phase 1/2, open-label clinical trial of the VTP-850 prime-boost 
immunotherapeutic in men with biochemical recurrence after definitive local therapy for prostate 
cancer. The trial will be conducted in up to 30 centres worldwide. 
Participants in all cohorts will receive the ChAdOx1-PCAQ component on Day 1 (prime) and the 
MVA-PCAQ component on Days 29 and 57 (boosts). Participants will be followed until the 
Month 6 Visit or start of new therapy such as ADT or until development of unequivocal 
metastatic prostate cancer. Participants who have a PSA response will be followed for an 
additional 18 months, up to 24 months from first dose, or until start of new therapy such as ADT 
or development of unequivocal metastatic prostate cancer. In the event that a participant 
experiences a confirmed PSA response but subsequently experiences PSA progression more than 
2 months after their final dose of VTP-850, an additional dose of MVA-PCAQ may be offered to 
the participant. 

 
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4.1.1 Phase 1 – Dose/Regimen Finding Phase 
Phase 1 will determine the recommended Phase 2 regimen (RP2R; dose level of both 
ChAdOx1-PCAQ and MVA-PCAQ, and route of administration of MVA-PCAQ) that will be 
used in Phase 2 and will follow a 3+3 design. 
Participants will be dosed according to Table 1 during the Screening and Intervention 
PeriodsTable 5. The first 3 participants will be enrolled in Cohort 1. Enrolment of the first 3 
participants in each cohort will be staggered by at least 9 days. The medical monitor will review 
the safety data for the previous participant, at least 7 days after the prime dose and after the first 
booster dose of VTP-850, before the corresponding dose is administered to the next participant. 
The safety review will include data from at least 7 days after each ChAdOx1-PCAQ prime dose; 
at least 7 days after the first booster MVA-PCAQ dose if administered IM; and at least 14 days 
after the first booster dose of MVA-PCAQ if administered IV. If 1 or more of the 3 participants 
has a dose limiting toxicity (DLT), 3 additional participants may be enrolled into Cohort 1. If 
there is no DLT after the first dose of VTP-850 in the first 3 participants, 3 participants will be 
enrolled into each of Cohorts 2 and 3 concurrently, with the first participants in Cohorts 2 and 3 
staggered by at least 9 days to allow for medical review.  
If DLT is not seen in more than 1 participant in Cohort 2 after the first dose of VTP-850, then an 
additional 3 participants will be enrolled into Cohort 2. Safety data for the DLT period following 
each booster dose will be assessed by the medical monitor prior to the corresponding booster 
dose being administered to additional participants. 
If DLT is not seen after the first dose of VTP-850 in more than 1 participant in Cohort 3, then an 
additional 3 participants will be enrolled into Cohort 3. Safety data for the DLT period following 
each booster dose will be assessed by the medical monitor prior to the corresponding booster 
dose being administered to additional participants. 
A total of 6 participants in each of Cohorts 2 and 3 will be dosed with MVA-PCAQ on Day 29 
and Day 57. Therefore, participants who withdraw before dosing, before completion of dosing or 
who have dose delays will be replaced (unless the reason for not completing dosing per protocol 
is related to a stopping rule criteria being met). 
If the safety of one or more cohorts is acceptable after all participants have been followed 
through the DLT period after the first booster dose of VTP-850, then a Phase 2 dosing regimen 
will be selected based on safety data, and recruitment to Phase 2 will be opened. 
A Safety Monitoring Committee (SMC) consisting of the Medical Monitor, sponsor physician, a 
prostate cancer physician not participating in the trial, and at least 2 investigators will review 
cumulative safety data and decide whether to enrol each cohort in Phase 1 and whether to open 
enrolment in Phase 2, and will also choose the RP2R.  The SMC will evaluate all events that 
meet the DLT criteria, taking into consideration the outcome and recovery time of each event. 
The DLT evaluation period ends 7 days after each IM injection and 14 days after each IV 
injection of MVA-PCAQ. 
A DLT is defined as any of the following toxicities that occur during the DLT evaluation period 
and are considered related to trial intervention (Grading is per CTCAE Version 5.0): 

 
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• 
Grade 4 or fatal AE  
• 
Grade 3 or greater hematologic AE that does not recover to Grade 1 or baseline Grade 
within 72 hours 
• 
Grade 3 or greater hepatic and renal dysfunction that does not improve to ≤ Grade 2 within 
7 days  
Grade 3 or greater AE affecting heart, lung or Central Nervous System (CNS) of any duration 
(including encephalopathy as defined by Immune Effector Cell Encephalopathy [ICE] or Immune 
Effector Cell -Associated Encephalopathy criteria [ICAN])  
• 
Grade 3 or greater cytokine release syndrome (CRS) that does not improve to ≤ Grade 2 
within 72 hours  
• 
Grade 3 or greater clinical AE other than heart, lung or CNS toxicity, hepatic or renal 
dysfunctions, not resolving to <Grade 2 within 72 hours 
4.1.2 Phase 2 – Main Phase 
Phase 2 of the trial will consist of 2 sequential stages. 
In Stage 1 of Phase 2, 19 additional participants will be enrolled at the chosen Phase 2 regimen. 
If 4 or more of the 25 participants at the RP2R (out of the 19 Phase 2 participants and the 
6 Phase 1 participants who received the same dose regimen according to the dosing schedule) 
have a PSA response, Stage 2 will be opened to enrolment. If 3 or fewer of the 25 participants 
receiving the RP2R have a PSA response, no further participants will be enrolled. PSA response 
is defined as ≥50% reduction in serum PSA compared to baseline at any time, measured at two 
consecutive timepoints, at least 2 weeks apart. The decision to open recruitment in Stage 2 will 
be made by the SMC after reviewing available safety and efficacy data after at least 
4 participants have exhibited a PSA response. 
4.1.3 Selection of Phase 2 Regimen 
This trial will test 2 dose levels of ChAdOx1-PCAQ and 2 dose levels of MVA-PCAQ delivered 
IM and one dose level of MVA-PCAQ delivered IV. 
Based on previous experience with vaccines and immunotherapeutics made with the ChAdOx1 
vector, it is expected that the higher dose level of ChAdOx1-PCAQ (2.5×1010 viral particles [vp]; 
Cohorts 2 and 3) will be more immunogenic and therefore will be chosen over the lower dose if 
both have acceptable safety. Similarly, for IM administration of MVA-PCAQ, the higher of the 
2 IM doses (2×108 plaque forming units [pfu] IM; Cohort 2) is expected to be more 
immunogenic and will be chosen over the lower dose if both have acceptable safety. 
Based on previous preclinical and clinical experience with vaccines and immunotherapeutics 
made with the MVA vector used as a booster, it is expected that the IV route of administration 
will result in enhanced T cell responses and better delivery of T cells to tissues, resulting in 
better efficacy. Therefore, the IV route of administration of MVA-PCAQ (Cohort 3) will be 
chosen over the IM route if both have acceptable safety.  

 
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4.1.4 Duration of Trial for Participants 
The trial consists of the following periods: 
• 
Screening Period: Up to 42 days from informed consent until VTP-850 prime dose. 
• 
Intervention Period: From VTP-850 prime dose until the Day 91 Clinic Visit. 
Short-term Follow-up Period: All participants will be followed monthly from the end of the 
intervention period until the Month 6 Visit or until start of new therapy such as ADT or 
development of unequivocal metastatic prostate cancer, if sooner. If a participant does not have a 
PSA response by their Month 6 visit, they will complete their EoT visit and will not enter the 
Long-term Follow-up Period. 
Long-term Follow-up Period: Participants who have PSA response will be followed for an 
additional 18 months, up to 24 months from first dose, or until start of new therapy such as ADT 
or development of unequivocal metastatic prostate cancer, if sooner. Clinic visits will be monthly 
to Month 12 and bimonthly thereafter. If a participant has a significant decrease in PSA but does 
not meet the criteria for a PSA responder e.g., the confirmatory measurement is not yet performed, 
discuss with the Medical Monitor whether the participant should continue follow-up. 
4.1.5 Safety Review During the Trial 
The Medical Monitor will review the trial data throughout the trial. 
The SMC will review the trial data periodically and make recommendations as detailed in 
Appendix A1.5.  
4.1.6 Pausing/Stopping Rules 
The trial will be temporarily paused and there will also be an unscheduled review of trial data by 
the SMC in the event of one or more of the following at any time during the trial:  
A CTCAE Grade 4 or 5 AE that is considered related to either component of VTP-850 
An SAE that is considered related to either component of VTP-850 
Death that occurs within 30 days of receiving either component of VTP-850 
The regulatory authority and independent ethics committee (IEC)/institutional review board 
(IRB) will be notified of a temporary halt according to local requirements. If, following review 
of data, a recommendation is made by the SMC to resume trial enrolment and VTP-850 
administration, the SMC will record their judgment in a memorandum to the trial file. The SMC 
memorandum will be forwarded to the investigators. 
If the trial is terminated early, the regulatory authority and IEC/IRB will be notified according to 
local requirements. 
4.1.7 Progression after Initial PSA Response 
In the event that a participant experiences a confirmed PSA response but subsequently 
experiences PSA progression more than 2 months after their final dose of VTP-850, an 

 
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additional dose of MVA-PCAQ may be offered to the participant if the investigator believes it 
may be in the participant’s best interest, after discussion with the medical monitor and agreement 
of the SMC. In this case, the participant will have an additional dosing visit which will include 
the events done on the Day 57 Dosing Visit in the Schedule of Assessments (SoA; see Table 1). 
Additional follow-up visits 1, 7, and 14 days after the additional dose will include the 
assessments done on the Day 58, Day 64, and Day 71 Visits in the SoA,. Subsequently they will 
continue to follow the SoA from the Day 91 Clinic Visit for their remaining time on trial 
(Section 1.3). Participants will be followed up to the Month 6 visit following the additional dose 
of VTP-850 or, if a PSA response is seen, for up to 24 months following the first dose of VTP-
850, or until start of new therapy such as ADT or development of unequivocal metastatic 
prostate cancer, at which point an End of Trial (EOT) visit will be performed.   
In order to perform sufficient follow-up post dose, the latest a participant can qualify for an 
additional MVA-PCAQ dose is using the blood test taken at the Month 18 visit.  
 
Justification for Dose 
The doses/regimens chosen for evaluation in this trial are provided in Table 4. 
The doses of each component and the dosing intervals chosen for this trial are based on historical 
data from previous studies of other products made with the same vectors. MVA boosts and 
prolongs the CD4+ and CD8+ T cells induced by ChAdOx1. This heterologous prime/boost 
immunotherapeutic regimen has been safe and immunogenic when used with products for other 
indications. ChAdOx1, including doses up to 5×1010 vp, and MVA, including doses up to 
2.5×108 pfu IM and up to 1×109 pfu IV, were evaluated in various indications.[6-9,12]  
4.2.1 Selection of ChAdOx1-PCAQ Target Dose 
The target ChAdOx1-PCAQ dose level selected for this trial is 2.5×1010 vp, based on the review 
of doses employed in other programs employing the ChAdOx1 platform in which this dose level, 
or higher, of ChAdOx1-based products has been safely administered: 
This is the same dose as the ChAdOx1 component of VTP-800, a prostate cancer 
immunotherapeutic that was made with the same ChAdOx1/MVA platform as VTP-850 and which 
included only the 5T4 oncofoetal antigen. It was safely administered in 2 clinical trials at 
University of Oxford. 
Two dose levels of ChAdOx1-HBV were studied in trial HBV001 (2.5×109 vp and 2.5×1010 vp). 
Safety data were reviewed from HBV001 by the SMC, and the higher dose was chosen to use in 
trial HBV002. 
• 
Over one billion people have been immunised with a ChAdOx1-vectored COVID-19 
vaccine at a dose of 5×1010 vp.[13] 
Safety and immunogenicity data from an additional clinical trial, MERS001 (NCT03399578), 
using the ChAdOx1 vector at this dose, also helped inform dose selection. 

 
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4.2.2 Selection of MVA-PCAQ Doses and Regimen 
The target MVA-PCAQ doses selected for this trial are 2×108 pfu for IM administration and 
2×107 pfu for IV administration, based on the review of historical data from previous studies in 
other programs employing the MVA platform. 
• 
In the completed studies of VTP-800, the prostate cancer immunotherapeutic that was 
made with the same ChAdOx1/MVA platform as VTP-850 and which included only the 
5T4 oncofoetal antigen, booster doses of MVA.5T4 were safely administered IM in 
2 clinical trials at University of Oxford at a dose of 1.2×108 pfu in the first trial, in 
patients with early phase prostate cancer, and at a dose of 2×108 pfu in the second trial, in 
patients with advanced prostate cancer. 
• 
One dose level of MVAHBV fixed at 1×108 pfu is being administered IM in the ongoing 
HBV002 trial. 
A dose of 1.5×108 pfu MVA was administered IM to nearly 2,000 healthy participants in 
influenza studies conducted by Oxford University and Barinthus Biotherapeutics . 
An MVA-vectored smallpox vaccine was approved in the US in 2019. JYNNEOS (IMVANEX, 
IMVAMUNE) is a vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic 
(MVA-BN). Each 0.5 mL dose is formulated to contain 0.5×108 to 3.95×108 infectious units of 
MVA-BN live virus. The overall clinical trial program included 22 studies and a total of 7859 
individuals 18 through 80 years of age who received at least 1 dose of JYNNEOS. 
4.2.3 Justification for Intravenous Administration of MVA-PCAQ 
In addition to IM dosing, which has been used in the studies described in the previous section, 
the booster doses of MVA-PCAQ will also be administered IV to investigate whether this route 
of administration might lead to increased efficacy. 
Preclinical studies have demonstrated that IV administration of some vaccines, including 
MVA-based constructs, can induce superior immunogenicity compared with subcutaneous or IM 
routes. Studies of a prophylactic vaccine for malaria (ChAd63-ME-TRAP/MVA-ME-TRAP) in 
mice, which used a similar prime-boost vaccination regimen, showed that changing the route of 
administration of the booster vaccine from IM to IV resulted in delivery of higher numbers of 
resident memory T-cells to the liver and improvement of efficacy against sporozoite challenge. A 
clinical trial of this vaccine at University of Oxford, in which participants received the booster 
vaccine intravenously, showed enhanced T cell responses to the malaria antigens in the vaccine 
(personal communication). 
In a first-in-human trial at the National Institutes of Health Clinical Center [12], 13 cancer 
patients received IV MVA-BN-brachyury-TRICOM, an MVA vector-based therapeutic cancer 
vaccine designed to induce an immune response against brachyury, which is overexpressed in 
many solid tumours. The maximum administered dose was 1×109 infectious units every 3 weeks 
for 3 doses. No DLTs were observed, and no SAEs were attributed to the vaccine. The maximum 
tolerated dose was not reached. One patient achieved a partial response. 

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Scientific Rationale for Trial Design 
Barinthus Biotherapeutics is developing a prime-boost immunotherapeutic strategy using 2 
non-replicating viral vectors to deliver immunogens in various indications: ChAdOx1 followed 
by boosting with a heterologous vector, MVA, containing the same immunogens. These vectors 
have been shown to induce high magnitude CD4+ and CD8+ T-cell responses and to generate 
lasting cell-mediated immunity.[5-9] 
Adenoviral vectors are exceptional priming vectors but there is a concern that anti-vector 
immunity could interfere with boosting the immune response when the ChAdOx1 vector is used 
repeatedly at short intervals. For this reason, product developers often use a different vector 
(known as a heterologous prime-boost) to augment the levels of the induced T cells.[10,11] 
Previous studies have shown that heterologous prime-boost regimens employing different 
vectors tend to produce more potent T-cell responses in nonhuman primates and humans than do 
homologous prime-boost regimens. 
VTP-850 has been designed following a Phase 1/2 clinical trial with VTP800, a prime-boost 
regimen with ChAdOx1 and MVA but encoding 5T4 only. Barinthus Biotherapeutics designed 
VTP-850 to induce a broader immune response by encoding multiple antigens (PSA, PAP, 
STEAP1, 5T4) to reduce the ability of cancer cells to evade the immune response by mutating or 
losing expression of any one antigen. These components are known as ChAdOx1-PCAQ and 
MVA-PCAQ. 
The dose escalation design including a small number of participants used in the dose/regimen 
finding phase is standard in first-in-human studies to minimise exposure to ineffective or poorly 
tolerated doses. 
Both ChAdOx1-PCAQ and MVA-PCAQ will be administered by IM injection. MVA-PCAQ 
will also be administered IV in one dose regimen cohort because preclinical data and previous 
clinical data suggest that boosting by the IV route might lead to increased efficacy. 
5 
TRIAL POPULATION 
Prospective approval of protocol deviations to eligibility criteria, also known as protocol waivers 
or exemptions, is not permitted. 
Inclusion Criteria 
Participants are eligible to be included in the trial only if all of the following criteria apply: 
Age 
1. Males aged 18 years and above at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Histologically or cytologically confirmed adenocarcinoma of the prostate.
3. Has undergone primary therapy for prostate cancer (radical prostatectomy and/or definitive
external beam radiation and/or brachytherapy). Salvage external radiation therapy (XRT)
following radical prostatectomy >6 months prior to Day 1 is allowed.

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4. No further local therapy to prostate or systemic therapy for prostate cancer and no metastasis-
directed therapy for PSA-positron emission tomography (PET) positive lesions planned within
4 months after the first dose of VTP-850.
5. Serum testosterone >175 ng/dL.
6. Nonmetastatic (M0) disease and no evidence of prostatic bed recurrence verified by whole
body bone scintigraphy and either computed tomography (CT) or magnetic resonance imaging
(MRI). Note that a positive PSMA PET does not exclude the participant if the conventional
scans are negative.
7. Serum PSA of >0.3 ng/mL for participants with prior radical prostatectomy (with or without
salvage radiotherapy), or serum PSA of 2 ng/mL above nadir for participants with prior
external beam radiation or brachytherapy.
8. PSA doubling time ≤12 months.
9. Not planning to start ADT for at least 4 months after Day 1.
10. Eastern Cooperative Oncology Group (ECOG) Score 0 or 1.
11. Baseline laboratory parameters must meet the following criteria:
•
Haemoglobin ≥110 g/L
•
White cell count ≥2.0×109/L
•
Absolute neutrophil count ≥1.5×109/L
•
Lymphocytes ≥0.9×109/L
•
Platelets ≥100×109/L
•
Creatinine ≤1.5×upper limit of normal (ULN) OR calculated creatinine clearance
≥50 mL/min by the Cockcroft Gault formula
•
Total bilirubin ≤1.5×ULN, (total bilirubin >1.5×ULN is acceptable if total bilirubin is
fractionated and direct bilirubin < 35%)
•
Alanine aminotransferase ≤1.5×ULN
•
Aspartate aminotransferase ≤1.5×ULN
•
Troponin T within normal range
•
HbA1c <7 %
Sex and Contraceptive/Barrier Requirements 
12. Agrees to the following during the trial and for at least 65 days after the last dose of VTP-850:
•
Refrain from donating sperm
PLUS, either 
•
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent
on a long-term and persistent basis) and agree to remain abstinent
OR 

 
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• 
Agrees to use a male condom when having sexual intercourse with a woman of 
childbearing potential, and should also be advised of the benefit for a female partner to use 
a highly effective method of contraception as a condom may break or leak 
Other Inclusions 
Agrees to comply with all scheduled visits, VTP-850 administration plan, laboratory tests, lifestyle 
considerations and other trial procedures. 
 
 
Exclusion Criteria  
Participants are excluded from the trial if any of the following criteria apply: 
Cancer History 
1. Any other prior malignancy within the past 5 years except for basal cell or squamous 
epithelial carcinomas of the skin that have been resected with no evidence of metastatic 
disease for 3 years. 
Medical Conditions 
2. Unstable medical condition, drug or alcohol abuse, or medical or psychiatric condition that in 
the opinion of the investigator would affect the safety of the participant or the evaluation of 
the data or interfere with adherence to the trial requirements. 
3. Significant history of or current cardiovascular, respiratory, renal, gastrointestinal, 
endocrinological, haematological or neurological disorders constituting a risk when taking the 
trial intervention or interfering with the interpretation of data; cardiac event or heart failure in 
the previous 6 months. 
4. Current or chronic history of liver disease. This includes but is not limited to: hepatitis virus 
infections, cirrhosis, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, 
autoimmune hepatitis, hemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency, primary 
biliary cholangitis, primary sclerosing cholangitis or any other liver disease considered 
clinically significant by the investigator. (Note that history of hepatitis C infection, Gilbert’s 
syndrome or non-alcoholic fatty liver not associated with steatohepatitis are not exclusions. In 
line with Exclusion Criterion 10, active hepatitis C infection is exclusionary.) 
5. Active autoimmune disease that has required systemic treatment in past 2 years with use of 
disease modifying agents, chronic corticosteroids (>14 days) or immunosuppressive drugs. 
Note that hormone replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency) is allowed. 
6. History of severe allergy to eggs or history of severe reaction to any previous vaccination that 
required medical attention. 
7. Medical history that could increase the participant’s risk of reaction to a vaccine, including but 
not limited to capillary leak syndrome, transverse myelitis, multiple sclerosis, Guillain Barré 
syndrome, significant thrombocytopenia, thrombosis with thrombocytopenia syndrome (also 
termed vaccine-induced thrombotic thrombocytopenia), heparin-induced thrombocytopenia, 
or hereditary angioedema, acquired angioedema or idiopathic angioedema. 

 
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8. Any immunocompromised state, or history of solid organ or stem cell transplantation. 
9. Active infection requiring parenteral antibiotic therapy or causing fever (temperature 
≥38.0˚C) within 7 days prior to Day 1, or unexplained fever (temperature ≥38.0˚C) within 7 
days prior to Day 1. 
10.  Known history of infection with hepatitis B virus, or human immunodeficiency virus, or 
active hepatitis C virus infection (antibody and RNA positive). 
Prior/Concomitant Therapy 
11.  Received XRT following radical prostatectomy within 6 months prior to Day 1. 
12.  Received ADT outside of the initial primary therapy.  
13.  Prior chemotherapy or immunotherapy (including vaccines or checkpoint inhibitors) or 
experimental agent or participation in a clinical trial for prostate cancer with the exception of 
those taking part as primary treatment option. 
14.  Received a vaccine with adenovirus vector within 3 months prior to Day 1. 
15.  Received any live vaccine within 30 days prior to Day 1, or planned vaccination to occur 
within 3 months after Day 1. 
16.  Received any non-live/inactivated vaccine within 14 days of Day 1 or planned non-live 
vaccination to occur within 10 weeks after Day 1. 
17.  Administration of immunoglobulins and/or any blood products within 28 days prior to Day 1.  
18.  Condition requiring systemic treatment with corticosteroids or other immunosuppressive 
medications within 14 days of first dose of VTP-850. Note that adrenal replacement doses are 
permitted. Inhaled and topical corticosteroids are allowed. 
19.  Received an investigational product or investigational surgical procedure in the 3 months prior 
to Day 1 or planned use during the trial period, or participation at any time in clinical trial for 
prostate cancer with exception of those taking part as primary treatment. 
Cardiovascular Risk Profile 
20.  Any significant cardiovascular conditions per the investigator within 6 months before study 
entry including but not limited to: myocardial infarction, stroke, New York Heart Association 
class III or IV heart failure, thromboembolic events, major cardiovascular or cerebrovascular 
procedures, history of cardiac valvular disease or other structural heart disease or any other 
condition that in the investigator’s opinion puts the participant at unacceptable risk to enter the 
study.  
21.  Participant with QT interval corrected for heart rate (QTc) determined using Fridericia’s 
formula (QTcF; QTcF = QT/[R-R interval {RR}^0.33]) > 470 msec and any other ECG 
findings deemed clinically significant at screening. 
22.  Uncontrolled hypertension that, in the opinion of the Investigator, puts participant at increased 
risk of a cardiovascular event at the time of screening.  
23.  Uncontrolled dyslipidemia that, in the opinion of the Investigator, puts participant at increased 
risk of cardiovascular event at the time of screening. 

 
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Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical trial is not 
subsequently entered in the trial. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE causally related to a screening procedure. 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened after discussion with the medical monitor.  
 
End of Trial Definition 
The end of the trial is defined as the date of the last visit of the last participant in the trial. 
6 
TRIAL INTERVENTIONS AND CONCOMITANT THERAPIES 
 
Identity of Investigational Products 
Details of the components of VTP-850 are provided in Table 4. 
Table 4 
Interventions Administered 
Intervention Name 
ChAdOx1-PCAQ 
MVA-PCAQ 
Investigational Medicinal 
Product Type  
Biologic (Immunotherapeutic) 
Biologic (Immunotherapeutic) 
Dose Formulation 
Suspension in a glass vial 
10 mM TRIS, 10 mM L-histidine, 
75 mM NaCl, 5% sucrose (w/v), 
1 mM MgCl2, 0.02% Polysorbate 80 
(w/v), 
0.1 mM ethylenediaminetetraacetic acid, 
0.5% ethanol (v/v), water for injections 
to 0.7 mL, pH 7.4 
Suspension in a glass vial 
sucrose 50 g/L, 50 mM NaCl, 
10 mM TRIS, 10 mM sodium glutamate, 
pH 8.0 
Route of Administration 
IM injection  
IM injection or 
Slow injection and flushing into IV line 
Use 
Experimental (Prime vaccination) 
Experimental (Booster vaccination) 
Sourcing 
Provided centrally by the sponsor 
Provided centrally by the sponsor  
Packaging and Labelling Will be provided in glass vials. 
Secondary packaged in a cardboard 
carton, with tamperproof seal. 
Each carton and vial will be labelled as 
per country requirement. 
Will be provided in glass vials. 
Secondary packaged in a cardboard 
carton, with tamperproof seal. 
Each carton and vial will be labelled as 
per country requirement. 
Target Concentration per 
Vial 
5.0×1010 vp/mL 
4.0×108 pfu/mL 
Abbreviations: IM=intramuscular, IV=intravenous, pfu=plaque forming units, TRIS=Tris (hydroxymethyl) 
aminomethane, v=volume, vp=viral particles, w=weight 

 
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Dose Levels Administered 
The doses/regimens chosen for evaluation in this trial are provided in Table 5. 
Table 5 
Phase 1 Trial Cohorts 
Cohort 
 
Number of Participants 
completing MVA-PCAQ 
dosing at Day 29 and 57  
Trial Intervention 
ChAdOx1-PCAQ 
Day 1 
MVA-PCAQ 
Days 29 and 57 
1 
3-6 
5×109 vp IM 
5×107 pfu IM 
2 
6 
2.5×1010 vp IM 
2×108 pfu IM 
3 
6 
2.5×1010 vp IM 
2×107 pfu IV 
Abbreviations: IM=intramuscular, IV=intravenous, pfu=plaque forming units, vp=viral particles 
 
Preparation, Handling, Storage, and Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit and storage for all trial intervention received, and any discrepancies are 
reported and resolved before use of the trial intervention. Any excursions from the storage 
conditions of the trial intervention as described in the label should be reported to Barinthus 
Biotherapeutics upon discovery along with any actions taken. The site should actively pursue 
options for returning the trial intervention to the storage conditions described in the labelling, as 
soon as possible. Once an excursion is identified, the trial intervention must be quarantined and 
not used until Barinthus Biotherapeutics provides permission to use the trial intervention. 
Specific details regarding the definition of an excursion and information the site should report for 
each excursion will be provided to the site in the pharmacy manual. 
Only participants enrolled in the trial may receive trial intervention, and only authorised site staff 
may supply or administer trial intervention. All trial intervention must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labelled storage conditions with access limited to the investigator and authorised site staff. 
The investigator, institution or the head of the medical institution (where applicable) is 
responsible for trial intervention accountability, reconciliation and record maintenance (i.e., 
receipt, reconciliation and final disposition records). Copies of these records will be provided to 
the sponsor for filing in the trial master file. 
Detailed instructions on administration of the components of VTP-850 are provided in the 
pharmacy manual. 
Further guidance and information for the final disposition of unused trial interventions are 
provided in the pharmacy manual. 
 
Measures to Minimise Bias: Randomisation and Blinding 
Not applicable. This is an open-label trial with no randomisation or blinding. 

 
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Trial Intervention Compliance 
All participants will be dosed at the site and will receive trial intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose administered 
in the clinic will be recorded in the source documents and electronic case report form (eCRF). 
 
Dose Modification 
No dose modifications of VTP-850 for individual participants are planned. 
 
Continued Access to Trial Intervention after the End of the Trial 
VTP-850 will not be made available to the participants after the trial is completed, as 
immunotherapeutic regimens of this type are intended to produce long-lasting immune responses 
and are not meant to require chronic use. 
 
Overdose or Incorrect Administration 
For this trial, any dose of VTP-850 greater than 50% above the intended dose is considered an 
overdose. 
An overdose or incorrect administration of either component of VTP-850 is not an AE unless it 
results in untoward medical effects. 
In the case of overdose the participant should be monitored for evidence of toxicity and standard 
supportive treatment provided based on any signs or symptoms experienced. There is no rescue 
medication. In the event of an overdose or other significant medication error that might impact 
the safety of the participant, the investigator should: 
Contact the medical monitor immediately 
Closely monitor the participant for any AE/SAE and laboratory abnormalities 
• 
Record any overdose or incorrect administration of VTP-850 in the eCRF as part of the 
administration information 
 
Rescue Medicine 
There is no rescue medication for VTP-850. 
 Prior and Concomitant Medications 
Any medication (including ADT, over-the-counter or prescription medicines, recreational drugs, 
vitamins and/or herbal supplements) that the participant receives from 30 days prior to Day 1 
until the End of Trial Visit should be recorded, along with: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 

 
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All vaccines that the participant received any time from 6 months prior to enrolment and any 
time during the trial should be recorded. Any prior adenoviral-vectored vaccine administered at 
any time should be recorded (e.g., Covid-19 vaccines made by Janssen/Johnson & Johnson or by 
AstraZeneca). 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  
Concurrent administration of certain agents might confound efficacy and safety assessments. 
These agents include:  
• 
Immunosuppressants (such as cyclosporin, mycophenolate mofetil, tacrolimus). 
• 
Immunomodulators used in autoimmune conditions (such as rituximab, anti-tumour 
necrosis factor inhibitors). 
High-dose systemic steroids at greater than physiological replacement dose (typically 
>10 mg/day prednisone or equivalent). However, inhaled, otic and ophthalmic corticosteroids or 
localised injections (e.g., intra-articular, intrabursal) are typically not a problem. 
Medications should not be withheld if they are required for a participant’s medical care. Use of 
these drugs during the trial should be discussed with the medical monitor. 
Note: any condition requiring systemic treatment with corticosteroids or other 
immunosuppressive medications within 14 days of the first dose of VTP-850, other than   inhaled 
and topical corticosteroids, are exclusionary (exclusion criterion 18, Section 5.2). 
Vaccines may interfere with the response to each other if administered too closely together. The 
following restrictions apply unless the investigator considers a vaccine to be medically indicated 
for the participant. Exceptions to these restrictions should be discussed with the medical monitor 
so that optimal timing of the vaccine in relation to VTP-850 can be discussed. 
Live vaccines should not be administered within 30 days before or after either component of VTP-
850 
Inactivated or non-live vaccines (e.g., mRNA vaccines) should not be administered within 14 days 
of either component of VTP-850 
Adenoviral-vectored vaccines should not be administered within 3 months before or after the 
ChAdOx1-PCAQ component of VTP-850 
  Contraindications/Delay to Dosing 
If the participant has an acute illness (moderate or severe illness with or without fever) or a fever 
(temperature ≥38.0°C) at the scheduled time or within 48 h before VTP-850 is to be 
administered, administration of the relevant component should be temporarily delayed. Trial 
intervention may be administered to that participant once the condition(s) has/have resolved, 
even if subsequent administration of components of VTP-850 will fall outside of the visit 
windows specified in the relevant SoA (Table 1). Delays in VTP-850 administration should be 
discussed with the Medical Monitor so that the optimal timing of administration and subsequent 
assessments can be agreed upon. See Section 7.1 for permanent discontinuation of trial 
intervention. 

 
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 Delay to Dosing Due to Study Pause 
Participants whose scheduled dosing of MVA-PCAQ is delayed due to a study pause during the 
Phase 1 portion of the study will be offered to recommence dosing and follow the SoA from Day 
57. These participants will also be replaced to ensure that 6 participants are dosed in each of 
Cohorts 2 and 3, to allow for a meaningful assessment at the end of Phase 1. 
7 
DISCONTINUATION OF TRIAL INTERVENTION AND PARTICIPANT 
DISCONTINUATION OR WITHDRAWAL 
Discontinuation of specific sites or of the trial as a whole are detailed in Appendix 1. 
 
Discontinuation of Trial Intervention 
It may be necessary for a participant to permanently discontinue trial intervention. Trial 
participants who present with at least one of the following VTP-850 discontinuation criteria 
listed below will be withdrawn from further trial intervention but will remain in the trial to be 
evaluated for safety, immunogenicity and efficacy, according to their PSA response and SoA 
(Section 1.3). 
Ulceration, abscess or necrosis at the site of injection of trial VTP-850 
Any CTCAE > Grade 3 AE considered related to VTP-850 and persisting continuously at > Grade 
3 for >72 h, with the exception of Grade 3 laboratory test abnormalities that improve to Grade 1 
or baseline grade within 14 days 
• 
An SAE considered related to VTP-850 
• 
Acute allergic reaction attributed to the administration of VTP-850 
If the participant requests discontinuation of further dosing with VTP-850, it must be 
documented on the appropriate eCRF and in the medical records whether the participant is 
discontinuing also from trial procedures, post-intervention trial follow-up, and/or future 
collection of additional information. 
 
Participant Discontinuation/Withdrawal from the Trial 
A participant may withdraw from the trial at any time at his own request or may be withdrawn at 
any time at the discretion of the investigator for safety, behavioural, disease-management (for 
example, in the case of rapid PSA progression, a participant may need to discontinue the trial to 
consider other treatment options) or compliance reasons.  
At the time of discontinuing from the trial, if possible, an End of Trial visit should be conducted, 
as shown in the SoA (Section 1.3). 
The participant will be permanently discontinued from the trial intervention and the trial at that 
time. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 

 
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If a participant withdraws from the trial, he may request destruction of any samples taken and not 
tested, and the investigator must document this in the site trial records. 
 
Lost to Follow-up 
A participant will be considered lost to follow-up on the date of latest successful contact if he 
repeatedly fails to return for scheduled visits and is unable to be contacted by the trial site. 
The following actions must be taken if a participant fails to return to the clinic for a required trial 
visit: 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit schedule, 
and ascertain whether the participant wishes to and/or should continue in the trial. 
Before a participant is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls, and if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he will be considered to have 
withdrawn from the trial.  
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants enrolled, including those who 
did not get trial intervention. Public sources may be searched for vital status information. If vital 
status is determined as deceased, this will be documented, and the participant will not be 
considered lost to follow-up. Sponsor personnel will not be involved in any attempts to collect 
vital status information. 
8 
TRIAL ASSESSMENTS AND PROCEDURES 
• 
Trial procedures and their timing are summarised in the SoA (Section 1.3) 
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood count) 
and obtained before signing of the informed consent form (ICF) may be utilised for screening or 
baseline purposes provided the procedures meet the protocol-specified criteria and were 
performed within the timeframe defined in the SoA 
 
Intervention Assessments 
Participants will receive the relevant VTP-850 dose for their visit based on their Phase/cohort 
allocation, administered according to the pharmacy manual. 
All participants will be observed in the clinic for at least 30 min post-dose in case of immediate 
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The following will be performed post-dose: 
• 
Vital signs (pulse rate, blood pressure and temperature) will be measured at approximately 
30 min post-dose 
• 
The participant will be assessed for local or systemic reactions (e.g., change in vital signs, 
occurrence of pain or swelling at the injection site) 
 
Efficacy Assessments 
8.2.1 Serum Prostate-Specific Antigen  
Blood samples for high-sensitivity serum PSA will be assessed at the central laboratory. 
8.2.2 Tumour Imaging 
To assess eligibility (Inclusion Criterion #6, see Section 5.1), historic CT or MRI scans and bone 
scans may be used if performed within 3 months of Day 1. If no historic scan is available, a bone 
scan and a CT or MRI will be performed. 
Participants will be assessed by whole body bone scintigraphy and either CT or MRI at least 
approximately every 6 months on trial. The optimal type of radiographic assessment for each 
participant will be determined by the investigator. 
Specific imaging of the prostate bed is not required for every participant. If there is a question of 
locally persistent or recurrent disease, a directed MRI of the prostate or prostate bed and/or 
biopsy of the site is recommended.  Participants with evidence of prostatic bed recurrence will be 
excluded from trial participation.  
Metastasis-free Survival (MFS) will be determined based on the Prostate Cancer Working 
Group 3 (PCWG-3) criteria. If radiographic progression occurs, it should be recorded whether it 
was manifested by lesions in bone and/or nodes and/or viscera. 
8.2.2.1 Technetium-99 Bone Scan 
The use of 99mTc-methylene diphosphonate radionuclide bone scintigraphy is the standard for 
bone imaging to assess the presence or absence of metastasis. 
8.2.2.2 CT or MRI of Chest, Abdomen and Pelvis 
Imaging of the chest, abdomen and pelvis using a contrast-enhanced CT scan with ≤5 mm axial 
slices is advised. For those intolerant of contrast, a cross-sectional MRI scan of the abdomen and 
pelvis, with a noncontrast CT scan of the chest, may be considered. 
If there is a question of locally persistent or recurrent disease, a directed MRI of the prostate or 
prostate bed and/or biopsy of the site is recommended. 
Extraskeletal disease should be assessed by RECIST 1.1. To establish nonmetastatic (M0) status, 
per PCWG3 criteria.  

 
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It is recommended that the same standard imaging modalities (e.g., bone scan, CT and/or MRI) 
used to determine eligibility be used for monitoring the participant on trial. 
8.2.3 Assessment of Progression to Metastatic Disease Based on PCWG3 Criteria 
Tumour progression will be based on the PCWG3 criteria for nonmetastatic disease. MFS is 
defined as the time from date of first dose of VTP-850 until unequivocal metastatic disease by 
conventional imaging (CT/MRI and/or technetium-99 bone scan) or death from any cause, 
whichever occurs first. Note that MFS events do not include local progression events, 
e.g., progression in pelvic lymph nodes below the aortic bifurcation. 
Bone 
Bone lesions will be assessed by bone scintigraphy commonly performed with technetium-99. 
Documentation of radiographic evidence of metastatic disease should include the time of the 
unequivocal development of new sites on bone scintigraphy. Confirmation of additional lesions 
(2+2) is not required. 
Lymph Nodes 
Lymph nodes that were previously normal in size (<1.0 cm) or pathologic in size must have 
grown by at least 5 mm in the short axis from baseline or nadir and be ≥1.0 cm in the short axis 
to be considered to have progressed. If the node progresses to ≥1.5 cm in the short axis, it is 
pathologic and measurable. Nodes that have progressed to between 1.0 and <1.5 cm are 
pathologic subject to clinical discretion and are nonmeasurable.  
Visceral 
The date of first metastasis is the date on which an unequivocal visceral lesion by RECIST 1.1 is 
determined. No confirmatory scan is required. Visceral disease should be reported as being with 
or without other patterns of spread (node, bone). 
 
Exploratory Assessments 
8.3.1 Cellular Immune Response 
Immunogenicity samples (peripheral blood mononuclear cells; PBMCs) will be taken for 
planned and potential exploratory analyses at each of the timepoints according to the SoA 
(Section 1.3). These samples will not be required at sites not qualified to process PBMCs. 
Immunogenicity studies will include (but are not limited to) analysis of samples ex vivo by 
multiparameter flow cytometry (including Mean Fluorescence Intensity measurements) and 
ex vivo IFN-γ enzyme linked immunospot assays (ELISpot) assays. The latter may be used for 
specific epitope mapping. Additional immunogenicity assessments may be performed. 
Prostate cancer-specific CD4+, CD8+ and T cell subsets within PBMCs will be further defined 
by phenotypic markers of activation, differentiation, memory and functionality using 
multiparameter flow cytometry assays such as intracellular cytokine staining. Peripheral blood 
mononuclear cells will also be used in IFN-γ ELISpot assays to determine the breadth of prostate 

 
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cancer-specific T cell responses (defined by number of peptide pools or individual peptides 
recognised). These data may be used to build immunologic models of the immune system. 
Left over immunology blood samples may, with participant consent, be retained for future research 
related to ChAdOx1-PCAQ and MVA-PCAQ.  This additional consent is optional, will not be 
required for participation in the trial and may be withdrawn at any time. 
8.3.2 Biomarkers 
Biomarker samples will only be analysed after Phase 2 Stage 2 is opened following the SMC’s 
review of efficacy and safety data after at least 4 PSA responses have been confirmed among the 
25 participants treated at the RP2R. If 3 or fewer of the 25 participants have a PSA response at 
the RP2R in Stage 1, biomarker sample analysis may not be performed. 
The investigator should attempt to collect an historical prostate tumour sample for assessment of: 
• 
Microsatellite instability-high status, BRCA and other molecular markers 
• 
Expression level of the VTP-850 antigens (PSA, PAP, STEAP1, 5T4) in tumour samples 
Blood will be taken for the assessment of biomarkers including:  
• 
Circulating tumour DNA 
• 
Serum PSA-binding antibodies 
• 
Anti-antigen antibodies 
8.3.3 Serum PSA-binding and anti-antigen Antibodies 
Serum PSA-binding and anti-antigen antibodies will be evaluated in blood samples collected 
from all participants according to the SoA (Section 1.3), using a validated assay method. 
8.3.4 PSMA scan 
PSMA scans are not required at baseline, but if a participant has had a PSMA scan in the 
previous 3 months or if they have ever had a PSMA scan showing lesions, the result of the 
PSMA scan should be collected in the eCRF. Optional PSMA scans will be performed to assess 
lesions in the subset of participants who had lesions on PSMA scan at baseline and who have a 
50% reduction in PSA from baseline on trial. The optional PSMA scan may be performed at any 
time during the trial after a PSA response is documented. 
If a participant has a PSMA scan on trial and it shows progression, the participant should also be 
assessed by standard radiography to confirm progression. 
 
 Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.4.1 Vital Signs 
Vital signs will be performed as per the SoA 

 
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• 
Vital signs will include temperature, systolic and diastolic blood pressure, and pulse. Blood 
pressure and pulse will be measured in a sitting position after 3 min rest 
8.4.2 Physical Examinations 
A complete physical examination will be performed at screening and will include, at a minimum, 
assessments of the cardiovascular, gastrointestinal and lymphatic systems. Height and weight 
will also be measured and recorded 
A symptom-directed physical examination will be performed as per the SoA 
Investigators should pay special attention to clinical signs related to previous serious illnesses 
and any symptoms or signs potentially pertaining to cardiotoxicity 
Results will be recorded as normal, abnormal and not clinically significant, or abnormal and 
clinically significant 
8.4.3 Clinical Laboratory Assessments 
Scheduled clinical laboratory assessments will be performed and samples will be sent to a central 
laboratory, with the exception of troponin T which will be performed by local laboratories. 
• 
Unscheduled or emergency laboratory assessments may be performed using a local 
laboratory if needed to ensure rapid delivery of test results, otherwise unscheduled study 
laboratory assessments will be done at the central laboratory. 
• 
See Appendix 2 for the list of clinical laboratory tests to be performed and the SoA 
(Section 1.3) for the timing and frequency. 
• 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the trial as an AE. The laboratory reports 
must be filed with the source documents.  
• 
Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant unless judged by the investigator to be more severe than expected 
for the participant’s condition. 
• 
All laboratory tests with values considered clinically significantly abnormal after the first 
dose with VTP-850 in the trial should be repeated until the values return to normal or to 
baseline grade or are no longer considered to be required by the investigator or medical 
monitor. 
If clinically significant abnormal safety laboratory values do not return to normal/baseline grade 
within a period of time judged reasonable by the investigator, the aetiology should be identified, 
and discussed with the Medical Monitor. 
• 
If laboratory values from non-protocol-specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded in the eCRF. 

 
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8.4.4 Electrocardiograms 
12-lead ECG(s) will be obtained as outlined in the SoA (Section 1.3) using an ECG machine 
that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals. 
The investigator should review the result and assess as normal or abnormal; if abnormal, it 
should be assessed as clinically significant or not clinically significant. 
8.4.5 Echocardiogram 
An echocardiogram will be obtained as outlined in the SoA (Section 1.3). The Investigator 
should review the result and, at screening, assess if the participant is eligible for dosing. If a 
cardiac event is reported during the trial period, an additional echocardiogram should be 
performed at the earliest opportunity. 
 
8.4.6 Pregnancy 
• 
If the partner of a participant becomes pregnant within 2 months of a participant 
receiving a dose of VTP-850, the partner will be asked to provide signed informed 
consent for the collection of details of the pregnancy and outcome. 
If a pregnancy is reported, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor after obtaining the necessary signed informed consent from the 
female partner. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported as 
such. 
The pregnant female partner will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the pregnant female partner and the neonate, 
and the information will be forwarded to the sponsor. 
• 
Any post-trial pregnancy-related SAE considered reasonably related to the trial 
intervention by the investigator will be reported to the sponsor as described in 
Appendix 3. While the investigator is not obligated to actively seek this information in 
former pregnant female partners, he or she may learn of an SAE through spontaneous 
reporting. 
8.4.7 Other Safety Assessments 
On the day of each dose, during the telephone calls the day following administration of each 
component of VTP-850 and 7 days following the administration of ChAdOx1-PCAQ and at the 
7-day post-dose visits following administration of MVA-PCAQ, the investigator will assess the 
injection/IV site and ask the participant how they are feeling since receiving VTP-850. 

 
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• 
If a participant experiences necrosis or exfoliative dermatitis at the injection site or 
requires an Emergency Room visit or hospitalisation for severe injection site pain, the 
investigator must immediately notify the sponsor and, if it is determined to be related to 
the administration of the trial intervention, further administration will be discontinued in 
that participant (see Section 7.1). 
• 
To allow participants to obtain information on fever when not at site, they will be given a 
thermometer with instructions on how to measure temperature at home. Temperature will 
be measured at any time during the trial when fever is suspected. Fever is defined as a 
temperature of ≥38.0°C.  
9 
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, ADVERSE EVENTS OF 
SPECIAL INTEREST AND OTHER SAFETY REPORTING 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate 
or the participant’s legally authorised representative). 
The investigator and any qualified designees are responsible for detecting, documenting and 
recording events that meet the definition of an AE, adverse event of special interest (AESI), or 
SAE and remain responsible for following up all AEs and SAEs that are considered related to the 
VTP-850 administration or trial procedures, or that caused the participant to discontinue VTP-850 
or the trial. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the procedures 
for completing and transmitting SAE/AESI reports are provided in Appendix 3. 
 
Time Period and Frequency for Collecting AE, SAE and AESI Information 
Adverse Events 
All AEs will be collected from the start of the first VTP-850 administration, continuing until the 
Month 6 Visit (see Table 1 and Table 2).  
Serious Adverse Events and Adverse Events of Special Interest During the Trial Intervention 
and Follow-up Periods 
SAEs and AESIs (see Section 9.5) will be collected from the start of the first VTP-850 
administration until the last trial visit. All SAEs and AESIs will be recorded and reported to the 
sponsor or designee within 24 h, as indicated in Appendix 3. The investigator will submit any 
updated SAE data to the sponsor within 24 h of its being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the trial participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the trial, and he/she considers the event to be 
reasonably related to the trial intervention or trial participation, the investigator must promptly 
notify the sponsor. 
Medical Occurrences Prior to First Dose of VTP-850 
This trial enrols participants who are not receiving other therapy for their prostate cancer. There 
is no required washout period, and there is no prolonged screening period, or invasive or unusual 

 
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procedures required during the screening period. Therefore, collection of AEs or SAEs prior to 
dosing in this trial would not help the sponsor monitor the safety of the participants or 
understand the safety profile of the trial intervention. Medical occurrences that begin before the 
start of trial intervention but after obtaining informed consent will be considered part of the 
participant’s medical history/current medical conditions. However, any medical occurrence that 
begins before the start of trial intervention but after obtaining informed consent that meets the 
criteria for seriousness (Appendix 3) and is causally related to a screening procedure should be 
reported to the sponsor or designee following the SAE/AESI reporting procedure within 24 h. 
 
Follow-up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs that occur after the first VTP-850 
administration will be followed until resolution, stabilisation, the event is otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is provided in Appendix 3. 
 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a trial intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a trial intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IECs/IRBs, and investigators. 
An investigator who receives an individual case safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Individual case safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs or 
SAEs 
Progression of prostate cancer including radiographic evidence of progression will be captured as 
an endpoint and does not need to be reported as an AE or SAE. 
 
Adverse Events of Special Interest 
The following events have been identified as adverse events of special interest (AESI) for the 
purpose of expedited reporting to Sponsor during the conduct of this trial::  
• any cardiac event 

 
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• shortness of breath / dyspnoea 
• abnormal cardiac investigation or examination 
 
If a cardiac event is reported, blood should be taken for assessment of troponin T and C-reactive 
protein (CRP) and the participant should undergo an ECG and echocardiogram at the earliest 
opportunity along with any other appropriate assessments as determined by the Investigator.  
10 PHARMACOKINETICS  
Pharmacokinetic parameters are not evaluated in this trial. 
11 STATISTICAL CONSIDERATIONS 
The statistical analysis plan (SAP) will be finalised prior to database lock, and it will include a 
more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
  Statistical Objectives 
The primary objective is to demonstrate that VTP-850 has a reasonable safety and tolerability 
profile. No formal hypothesis will be tested.  
The secondary objectives include evaluating the presence and durability of PSA response to 
VTP-850. Estimated response rates and durability may be used for power and sample size 
purposes in subsequent trials. 
11.1.1 Multiplicity Adjustment 
The analyses associated with this trial are primarily descriptive in nature, and multiplicity 
adjustments have not been specified.  
11.1.2 Analysis sets 
• The intent-to-treat analysis set (full analysis set) will consist of all participants who are 
enrolled into the trial and who received at least one dose of VTP-850 
• The safety analysis set will consist of all participants who receive at least one dose of 
VTP-850 (data will be summarised according to the dose levels and regimens actually 
received) 
• The per-protocol analysis set will consist of all participants in the safety analysis set who 
received the correct trial intervention and who had no major protocol deviations that 
would potentially bias the trial’s analyses 
• The immunogenicity analysis set will consist of all participants who have available 
immunogenicity data to evaluate the immunogenicity endpoints and do not have any 
major protocol deviations that would impact the results of the immunological analysis 

 
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Assignment of participants to the analysis sets (and whether any participant or specific data from 
a participant will be excluded) will be determined at the pre-database-lock Data Review meeting. 
  Statistical Analyses 
11.2.1 General Considerations 
Most analyses will be descriptive in nature. Unless stated otherwise, continuous variables will be 
summarised using descriptive statistics (number of participants, mean, standard deviation, 
median, minimum and maximum values), and the number and percentage of participants will be 
presented for categorical variables. Data will be summarised by trial cohort and, where 
appropriate, overall. Immunogenicity and efficacy data may have additional statistical analysis, 
which will be detailed in the trial’s SAP. 
The SAP will describe and account for the occurrence of and extent of missing data and its 
possible impact on the trial analysis. 
11.2.2 Primary Endpoint Analysis 
Safety data will be summarised descriptively. Adverse Events are defined as those occurring 
after trial intervention administration. 
11.2.2.1 Adverse Events 
All AEs will be listed, including the verbatim description and the Medical Dictionary for 
Regulatory Activities (MedDRA) preferred term (PT) and system organ class (SOC). 
All AEs will be summarised by SOC and PT over the course of AE follow-up, as well as during 
the 28-day period following each administration of VTP-850. The incidence of AEs will be 
based on the numbers and percentages of participants with events. AEs will be further 
summarised by severity and relationship to trial intervention. 
An overall summary of AE incidence will also be presented by trial cohort and overall to include 
the number and percentage of participants with at least one: AE, treatment-related AE, Grade 3 
to Grade 5 AE, death, SAE, treatment-related SAE, AE leading to trial intervention 
discontinuation and AE leading to trial discontinuation. 
Narratives will be written for any deaths, other SAEs, AESIs, AEs leading to trial intervention 
discontinuation and AEs leading to trial discontinuation. 
11.2.2.2 Laboratory Safety Tests 
Severity grading using CTCAE Version 5.0 will be assigned to laboratory safety values where 
applicable. Laboratory results in reported units and International System of Units (SI) units will 
be listed, including high and low flags, severity grades where applicable, the corresponding 
normal range and clinical significance. 

 
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Safety laboratory tests summaries will be based on results in SI units. Absolute and change from 
baseline results, including the worst change for each parameter for each participant, will be 
summarised using descriptive statistics. 
Treatment-emergent, out-of-range results with the corresponding severity grade, normal ranges, 
baseline results and clinical significance will be listed separately. Shift tables of the CTCAE 
grades will be used to show changes from baseline at each timepoint and the worst change in 
each participant. The number of participants showing shifts of at least 2 severity grades will be 
summarised. 
The number of participants with treatment-emergent clinically significant safety laboratory test 
results and safety laboratory test results of Grade 3 or 4 will be summarised. 
11.2.2.3 Vital Signs 
Absolute and change from baseline vital sign results, including the worst change for each 
variable for each participant will be summarised using descriptive statistics. Treatment-emergent, 
out-of-range results with the corresponding normal ranges, baseline results and clinical 
significance will be listed separately. The number of participants with treatment-emergent, 
clinically significant results will be summarised. 
11.2.3 Secondary Endpoint Analyses 
11.2.3.1 PSA Response to VTP-850 
The number, proportion, and 90% confidence interval (CI) of participants with a PSA response, 
defined as ≥50% reduction in serum PSA compared to baseline and measured twice 
consecutively, will be summarised by timepoint and overall. This will be further broken down by 
whether the participants had prior radical prostatectomy or prior external beam radiation. The 
maximum PSA reduction from baseline will be summarised, as well as by whether participants 
had prior radical prostatectomy, external beam radiation or brachytherapy.  
11.2.3.2 Durable PSA Response to VTP-850 at Month 8 
The number, proportion and 90% CI of participants with a durable PSA response at Month 8 will 
be summarised, among all participants and among those with a response by Month 6. Durable 
PSA response is defined as having follow-up through Month 8 and a confirmed PSA response 
without having PSA progression (i.e., an increase relative to nadir of ≥25% and an absolute 
increase of 0.2 ng/mL or more) on or before Month 8. This will be further summarised by 
whether the participants had prior radical prostatectomy, external beam radiation or 
brachytherapy. 
11.2.3.3 Duration of PSA Response to VTP-850 
Among those participants who experienced a PSA response, the duration of PSA response, 
defined as the time from first dose of VTP-850 to the date of PSA progression, will be 
summarised (n, median, interquartile range, minimum, maximum) and presented using a 

 
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Kaplan-Meier plot. Participants whose PSA response is ongoing upon the completion of 
follow-up will be censored at the time of their last follow-up visit with a non-missing PSA 
evaluation. An additional analysis will evaluate duration of PSA response, defined as the time 
from observation of PSA reduction of at least 50% to the date of PSA progression. 
This endpoint will be further summarised by whether the participants had prior radical 
prostatectomy, external beam radiation or brachytherapy. 
11.2.3.4 Metastasis-Free Survival and Time to Metastases 
The duration of MFS, defined as the time from first dose of VTP-850 to detection of metastatic 
disease or all-cause mortality, will be summarised (n, median, interquartile range, minimum, 
maximum) and presented using a Kaplan-Meier plot. Participants who have survived without 
development of metastatic disease by the end of follow-up will be censored at the time of their 
last follow-up visit with an evaluable assessment of metastatic disease. 
The duration of TTM, defined as the time from first dose of VTP-850 to detection of metastatic 
disease, will be summarised (n, median, interquartile range, minimum, maximum) and presented 
using a Kaplan-Meier plot. Participants who have not developed metastatic disease by the end of 
follow-up will be censored at the time of their last follow-up visit with an evaluable assessment 
of metastatic disease.  
These endpoints will be further summarised by whether the participants had prior radical 
prostatectomy, external beam radiation or brachytherapy. These endpoints will be further 
summarised for participants who experienced a PSA response. 
11.2.3.5 Time to Start of ADT for Participants with PSA Response 
Among those participants who experienced a PSA response, the time to initiation of ADT 
treatment (or when they have met the criteria to initiate ADT) will be summarised (number of 
participants, median, interquartile range, minimum, maximum) and presented using a 
Kaplan-Meier plot. Responders who have not started ADT or met the criteria to start ADT by the 
end of follow-up will be censored at the time of their last follow-up visit. 
This endpoint will be further summarised by whether the participants had prior radical 
prostatectomy or external beam radiation. This endpoint will be further summarised for 
participants who experienced a PSA response. 
11.2.4 Exploratory Endpoint Analyses 
Exploratory endpoints and planned analyses will be described in detail within the SAP. 
11.2.5 Other Analyses 
11.2.5.1 Disposition  
Participant disposition (such as the number screened, screen failed, treated, completed, 
discontinued from treatment and discontinued from trial), including reasons for withdrawal, if 
applicable, will be summarised descriptively.  

 
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11.2.5.2 Protocol Deviations  
Protocol deviations will be listed including the nature (e.g., missed procedure(s), early or late 
procedure(s), missed visits, visit performed out of protocol defined window, prohibited 
medication taken, trial intervention dosing deviation, inclusion/exclusion criteria deviations, 
participants not withdrawn but meeting withdrawal criteria, biological sample handling error, 
other) and major or minor classification.  
11.2.5.3 Demographics and Baseline Characteristics  
Demographics and baseline characteristics will be listed and summarised descriptively for 
participants in the safety analysis set.  
11.2.5.4 Prior and Concomitant Medications and Procedures 
Concomitant medications and procedures will be summarised by Anatomic Therapeutic 
Chemical classification. Both prior and concomitant medications and procedures will be listed. 
11.2.5.5 Medical History 
Medical history will be listed, including the verbatim description and associated MedDRA PT 
and SOC. 
  Interim Analysis 
Two interim reviews of trial data are planned.  
The first is a preliminary assessment of data from the 25 participants who received the RP2R 
through Stage 1 of Phase 2 to determine whether the trial has provided sufficient evidence of 
PSA response to warrant enrolment of an additional 100 participants in Phase 2, Stage 2. 
Enrolment in Stage 2 will begin following the SMC’s review of efficacy and safety data after at 
least 4 PSA responses have occurred among the 25 participants. 
In addition to this and other data reviews performed by the SMC (refer to Section 4.1.1), an 
interim analysis will be conducted once all participants enrolled in the Phase 2 portion of the trial 
have been followed through at least the Month 3 visit. The results from this interim analysis will 
solely be used for the purpose of planning future clinical trials and will not impact the conduct of 
this trial, i.e., the sample size of the ongoing trial will not expand as a result of this review. 
Further, given this is an open-label trial without a control arm, and the trial’s endpoints will only 
be evaluated in a descriptive manner upon trial completion, this interim look will not result in a 
penalty on any pre-planned alpha level. All secondary endpoints described above will be 
included in the interim analysis. 
 Sample Size Determination 
A total of approximately 144 participants will be enrolled. A sample size of approximately 
125 participants will be eligible for inclusion in the Phase 2 efficacy evaluation.  

 
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Twenty-five participants are to be included in the preliminary Stage 1 assessment to expand into 
Stage 2 of Phase 2 (i.e., the first 19 participants enrolled in Stage 1 and the 6 participants from 
Phase 1 receiving the RP2R according to the dosing schedule). If the true response rate (where 
response is defined as ≥50% reduction in serum PSA at any 2 consecutive post-baseline 
timepoints at least 2 weeks apart) associated with VTP-850 administration is ≥20%, 25 
participants will yield a 76.6% chance (i.e., power) of observing 4 or more responders. 
One hundred and twenty-five participants (combined Stage 1 enrolment as described above and 
Stage 2 enrolment in Phase 2) will yield the following 90% and 95% Confidence Intervals (CIs) 
for the true response rate based on the example observed response rates in Table 6. This Phase 2 
sample size has 89.3% power to rule out a null proportion of PSA responders of 10% using a 
two-sided exact test with a target significance level of 0.05 assuming a true response percentage 
of 20%. The null hypothesis response rate of 10% will be rejected if at least 20 PSA responders 
(16%) are observed amongst the 125 participants. 
The observed response rate and associated CIs will facilitate decision-making regarding whether 
to continue the program as well as the appropriate sample size for subsequent trials. 
 
Table 6 
Confidence Intervals for True Serum PSA Response Rate Based on Observed 
Response Rate (n=125) 
Observed Response Rate (%) 
90% Confidence Interval 
95% Confidence Interval 
0.10 
(0.059, 0.156) 
(0.054, 0.166) 
0.15 
(0.100, 0.213) 
(0.092, 0.225) 
0.20 
(0.143, 0.268) 
(0.134, 0.281) 
0.25 
(0.187, 0.322) 
(0.177, 0.335) 
0.30 
(0.233, 0.375) 
(0.221, 0.388) 
 
 

 
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12 REFERENCES 
1. Cappuccini F, Bryant R, Pollock E, et al. Safety and immunogenicity of novel 5T4 viral 
vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial. J 
ImmunoTher Cancer. 2020;8:e000928. doi: 10.1136/jitc-2020-000928. 
2. Artibani W, Porcaro AB, De Marco V, Cerruto MA, Siracusano S. Management of 
biochemical recurrence after primary curative treatment for prostate cancer: a review. 
Urol Int. 2018;100:251-262. doi: 10.1159/000481438. 
3. National Comprehensive Cancer Network®. 2021. NCCN clinical practice guidelines in 
oncology (NCCN Guidelines®-prostate cancer; version 3.202f2. [online] Available at: 
https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459 
4. George DJ, Sartor O, Miller K, et al. Treatment patterns and outcomes in patients with 
metastatic castration-resistant prostate cancer in a real-world clinical practice setting in 
the United States. Clin Genitourin Cancer. 2020;18(4):284-294. doi: 
10.1016/j.clgc.2019.12.019. Epub 2020 Jan 7. PMID: 32057714 
5. Ewer KJ, Lambe T, Rollier CS, Spencer AJ, Hill AV, Dorrell L. Viral vectors as vaccine 
platforms: from immunogenicity to impact. Curr Opin Immunol. 2016;41:47-54. doi: 
10.1016/j.coi.2016.05.014. Epub 2016 Jun 7. PMID: 27286566. 
6. Antrobus RD, Coughlan L, Berthoud TK, et al. Clinical assessment of a novel 
recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved 
Influenza A antigens. Mol Ther. 2014;22(3):668-674. doi: 10.1038/mt.2013.284. Epub 
2013 Dec 30. PMID: 24374965; PMCID: PMC3944330. 
7. Folegatti PM, Bittaye M, Flaxman A, et al. Safety and immunogenicity of a candidate 
Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, 
open-label, non-randomised, uncontrolled, Phase 1 trial. Lancet Infect Dis. 
2020;20(7):816-826. doi: 10.1016/S1473-3099(20)30160-2. Epub 2020 Apr 21. Erratum 
in: Lancet Infect Dis. 2020 May 12;: Erratum in: Lancet Infect Dis. 2020 Jun 8;: PMID: 
32325038; PMCID: PMC7172901. 
8. Folegatti PM, Ewer KJ, Aley PK, et al. Safety and immunogenicity of the ChAdOx1 
nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a Phase 1/2, single-blind, 
randomised controlled trial. Lancet. 2020;396(10249):467-478. doi: 10.1016/S0140-
6736(20)31604-4. Epub 2020 Jul 20. Erratum in: Lancet. 2020 Aug 15;396(10249):466. 
Erratum in: Lancet. 2020 Dec 12;396(10266):1884. PMID: 32702298; PMCID: 
PMC7445431. 
9. Berthoud TK, Hamill M, Lillie PJ, et al. Potent CD8+ T-cell immunogenicity in humans 
of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clin Infect Dis. 
2011;52(1):1-7. doi: 10.1093/cid/ciq015. PMID: 21148512; PMCID: PMC3060888. 
10. Lu S. Heterologous prime-boost vaccination. Curr Opin Immunol. 2009;21(3):346-351. 
doi: 10.1016/j.coi.2009.05.016. Epub 2009 Jun 6. PMID: 19500964; PMCID: 
PMC3743086. 

 
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11. Schneider J, Gilbert SC, Hannan CM, et al. Induction of CD8+ T cells using heterologous 
prime‐boost immunisation strategies. Immunol Rev. 1999;170:29-38. doi: 
10.1111/j.1600-065x.1999.tb01326.x. PMID: 10566139. 
12. DeMaria PJ, Lee-Wisdom K, Donahue RN, et al. Phase 1 open-label trial of intravenous 
administration of MVA-BN-brachyury-TRICOM vaccine in patients with advanced 
cancer. J Immunother Cancer. 2021;9(9):e003238. doi: 10.1136/jitc-2021-003238. PMID: 
34479925; PMCID: PMC8420671.  
13. European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk 
Assessment Committee (PRAC) 10 - 13 January 2022. Available at: 
https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-
assessment-committee-prac-10-13-january-2022 
 
 

 
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 Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations 
A1.1. 
REGULATORY AND ETHICAL CONSIDERATIONS 
This trial will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) international ethical guidelines 
o Applicable ICH Good Clinical Practice (GCP) guidelines 
o Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC 
before the trial is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of changes 
made to the trial design, except for changes necessary to eliminate an immediate hazard to trial 
participants.  
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to trial 
participants. 
The investigator will be responsible for the following: 
o Providing written summaries of the status of the trial to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies and procedures 
established by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the trial at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
A1.2. 
FINANCIAL DISCLOSURE 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the trial and for 
1 year after completion of the trial. 
A1.3. 
INFORMED CONSENT PROCESS 
The investigator or his representative will explain the nature of the trial, including the risks and 
benefits, to the participant and answer all questions regarding the trial. 
Participants must be informed that their participation is voluntary. Participants will be required to 

 
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sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the 
IRB/IEC or trial centre. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the trial and the date the written 
consent was obtained. The authorised person obtaining the informed consent must 
also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the trial. 
• A copy of the ICF(s) must be provided to the participant. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 42 days from the previous ICF signature date, or there is a new ICF including updated 
safety or trial information. 
A1.4. 
DATA PROTECTION 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 
The participant must be informed that his personal trial-related data will be used by the sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the participant who will be required to give consent for their data to be used as described in the 
informed consent  
The participant must be informed that his medical records may be examined by Clinical Quality 
Assurance auditors or other authorised personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
A1.5. 
SAFETY MONITORING COMMITTEE 
Participant safety will be continuously monitored by the SMC. 
The SMC, consisting of the sponsor trial physician, the Medical Monitor, a prostate cancer 
physician not participating in the trial, and at least 2 investigators will be appointed to review the 
trial data periodically or when needed and make recommendations concerning the continuation, 
modification or termination of the trial. 
• The timings of SMC meetings will be defined in a trial-specific SMC Charter. 
• The SMC will make recommendations about: 
o Opening each cohort in Phase 1 
o Choosing the regimen for Phase 2 and opening enrolment in Phase 2 
o Opening recruitment in Stage 2 of Phase 2, after reviewing available safety and 
efficacy data after at least 4 PSA responders have been identified 
o Altering the dose/ regimen (e.g., dropping back a dose level or dropping the 
second booster dose) 
o Pausing or stopping the trial 
o The institution of additional safety measures, if considered to be required 
 

 
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A1.6. 
DISSEMINATION OF CLINICAL TRIAL DATA 
• Barinthus Biotherapeutics will share anonymised trial data on a publicly available 
database, as per local regulations. 
Clinical Trial Reports (CSRs), periodic safety reports, and clinical trial summary reports will be 
disclosed after review by regulatory authorities. This includes access to Clinical Trial Reports 
from studies with negative outcomes and from terminated development programs. 
A1.7. 
DATA QUALITY ASSURANCE 
All participant data relating to the trial will be recorded on eCRFs unless transmitted to the 
sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by electronically signing the eCRF. 
• Guidance on completion of eCRFs will be provided. 
The investigator must permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy, including definition of trial critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote or on-site monitoring) will be described in the monitoring plan. 
The sponsor or designee is responsible for the data management of this trial, including quality 
checking of the data. 
• The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organisations). 
Records and documents, including signed ICFs, pertaining to the conduct of this trial must be 
retained by the investigator for 25 years after trial completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
A1.8. 
SOURCE DOCUMENTS 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with the 
source documents or the discrepancies must be explained. The investigator may need to request 
previous medical records or transfer records, depending on the trial. Also, current medical 
records must be available. 
Definition of what constitutes source data and its location will be agreed with the sites and 
documented. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
• Trial monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorised site personnel are accurate, complete and 
verifiable from source documents; that the safety and rights of participants are being 

 
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protected; and that the trial is being conducted in accordance with the currently 
approved protocol and any other trial agreements, ICH GCP and all applicable 
regulatory requirements. 
A1.9. 
TRIAL AND SITE CLOSURE 
The sponsor or designee reserves the right to close the trial site or terminate the trial at any time 
for any reason at the sole discretion of the sponsor. Trial sites will be closed upon trial 
completion. A trial site is considered closed when all required documents and trial supplies have 
been collected and a trial-site closure visit has been performed. 
The investigator may initiate trial-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a trial site by the sponsor or investigator may include but are not 
limited to: 
For trial termination: 
• Discontinuation of further trial intervention development 
For site termination: 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or local 
health authorities, the sponsor’s procedures or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• Total number of participants included earlier than expected 
If the trial is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities and any contract research organisation(s) 
used in the trial of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
A1.10. 
PUBLICATION POLICY 
The final trial report will be made available to the investigator for purposes of publications. The 
investigator and trial team must send all manuscripts, abstracts and presentations using data from 
this trial to the sponsor for review prior to their submission. The sponsor reserves the right to 
publish first or to delete any part or parts of the investigator’s materials deemed to be 
confidential or proprietary. 
 

 
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 Appendix 2: Clinical Laboratory Tests – Analytes and Laboratory Locations 
• The tests detailed in Table 7 will be performed by the central laboratory with the 
exception of troponin T which will be performed by local laboratories. 
Except for troponin T, local laboratory results are only required if the central laboratory results 
are not available in time for either trial intervention administration and/or response evaluation. If 
a local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a trial intervention 
decision or response evaluation, the results must be recorded. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
Additional tests may be performed at any time during the trial as determined necessary by the 
investigator or required by local regulations. 
Table 7 
Protocol-Required Laboratory Safety Tests 
Laboratory Tests 
Parameters 
Haematology 
Platelet count  
RBC indices: 
Mean corpuscular 
volume (MCV) 
Mean corpuscular 
haemoglobin (MCH) 
%Reticulocytes 
White blood cell (WBC) 
count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red blood cell (RBC) 
count 
Haemoglobin 
Haematocrit 
Biochemistry 
Blood urea nitrogen (BUN) 
Calcium 
Creatinine 
Glucose (non-fasting) 
Potassium 
Sodium 
Total protein 
Liver function tests 
Alanine aminotransferase (ALT) 
Alkaline phosphatase (ALP) 
Aspartate aminotransferase (AST) 
Total and direct bilirubin 
Markers for cardiac 
dysfunction or 
inflammatory response  
Troponin T 
C-reactive protein (CRP) 
Routine urinalysis 
• Specific gravity 
• pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick (read locally) 
• Microscopic examination (if blood or protein is abnormal) 
Investigators must document their review of each laboratory safety report. 
 

 
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 Appendix 3: AEs, AESIs and SAEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up and Reporting 
A3.1. 
DEFINITION OF AE 
AE Definition 
• An AE is any untoward medical occurrence in a participant or clinical investigation subject 
administered the investigational product and which does not necessarily have to have a causal 
relationship with this treatment. 
• An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the use of trial 
intervention, whether considered related to the investigational product. 
 
Events Meeting the AE Definition 
• Any clinically significant worsening of a pre-existing condition 
• An AE occurring from overdose of an investigational or marketed product, whether 
accidental or intentional 
• An AE occurring from abuse (e.g., use for non-clinical reasons) of an investigational or 
marketed product 
An event related to a medical procedure or associated with the discontinuation of the previous 
use of an investigational or marketed product required by protocol (protocol related AE) 
• Not all vital sign or laboratory abnormalities will be considered an AE. Usually these will 
be considered as an AE: 
o If CTCAE Grade 3 (severe) or greater in severity 
o If judged to be clinically significant by the investigator 
o If accompanied by clinical symptoms 
o If meeting the definition of an SAE 
o If resulting in dose interruption or discontinuation of trial intervention 
o If requiring specific treatment 
 
Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition 
• The disease/disorder being studied (prostate cancer) or expected progression, signs, 
or symptoms of the disease/disorder being studied, unless more severe than 
expected for the participant’s condition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 

 
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leads to the procedure is the AE 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the trial that do not worsen 
 
Recording Medical Occurrences Prior to Trial Dosing 
• Any medical occurrence that occurs after the participant has given their informed 
consent and prior to the start of the first dose of VTP-850, including clinically 
significant abnormalities found in screening assessments, will be considered part of 
the participant’s medical history. 
 
A3.2. 
DEFINITION OF AESI 
AESI Definition 
An AESI is defined as: 
• 
any cardiac event 
• 
shortness of breath / dyspnoea 
• 
abnormal cardiac investigation or examination 
 
A3.3. 
DEFINITION OF SAE 
An SAE is defined as any untoward medical occurrence that meets one of more of the 
criteria listed that occurs after the start of the first dose of VTP-850, or occurs after 
informed consent has been provided and is causally related to a trial procedure: 
Results in death (i.e., the adverse event caused or led to the fatality). Serious does not 
describe an event which hypothetically might have caused death if it were more severe 
a. Is life threatening 
The term life threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
b. Requires inpatient hospitalisation or prolongation of existing hospitalisation 
It required inpatient hospitalisation or prolonged hospitalisation beyond the expected length of 
stay. Hospitalisations for scheduled treatments and elective medical/surgical procedures 
related to a pre-existing condition that did not increase in severity or frequency following 
receipt of trial intervention, are not serious by this criterion. Hospitalisation is defined as a 
hospital admission or an emergency room visit for a period greater than 24 h 

 
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• Hospitalisation for social reasons or for elective treatment of a pre-existing 
condition that did not worsen from baseline is not considered an AE. 
c. Results in persistent or significant disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhoea, influenza, and accidental 
trauma (e.g., sprained ankle) that may interfere with or prevent everyday life functions but do 
not constitute a substantial disruption. 
d. Is a congenital anomaly/birth defect (i.e., an adverse finding in a child or foetus of a 
participant exposed to the trial intervention prior to conception or during pregnancy). 
Other medically significant events: 
• 
An adverse finding that may not result in death, threaten life or require 
hospitalisation (i.e., the adverse event does not meet any of the above serious 
criteria) may be considered an SAE when, based on appropriate medical judgment, 
they may jeopardise the participant and require medical or surgical intervention to 
prevent one of the serious outcomes listed in these criteria (e.g., allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in hospitalisation, or the 
development of drug dependency or drug abuse). 
A3.4. 
RECORDING AND FOLLOW-UP OF AE AND/OR SAE  
AE and SAE Recording 
• 
All AEs are recorded in the eCRF at all telephone and clinic visits until the Month 6 
visit. All AEs will be reported using a recognised medical term or diagnosis that 
accurately reflects the event. 
• 
Adverse events will be assessed by the investigator, or a medically qualified trial team 
member, for severity, relationship to VTP-850, action taken, outcome and whether the 
event meets criteria as an SAE according to the guidelines in this appendix. 
Assessment of Intensity 
• 
The severity of AEs and laboratory values will be graded according to the Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The scale shown in 
Table 8 will be used to assess severity of AEs not listed in the CTCAE. 
 
Table 8 
Severity Grading of Adverse Events not listed in CTCAE  
Grade 
Severity1 
1 
Mild  
Asymptomatic or mild symptoms; clinical or diagnostic observations only; or 
intervention not indicated. 

 
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2 
Moderate 
Minimal, local or non-invasive intervention indicated; limiting age-appropriate 
instrumental Activities of Daily Living (ADL)2. 
3 
Severe 
Severe or medically significant but not immediately life-threatening; hospitalisation 
or prolongation of hospitalisation indicated; disabling; limiting self care ADL3. 
4 
Lifethreatening 
Life-threatening consequences; urgent intervention indicated. 
5 
Fatal 
Death related to this AE 
1 A semi-colon indicates ‘or’ within the description of the grade 
2 Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
3 Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications and not 
bedridden. 
 
A change in severity of an AE will be recorded as a new AE with the outcome of the event prior 
to the change in severity stated as “change in severity”. The onset and resolution dates will 
encompass the duration of each severity.  
Note: It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Section A3.3. 
Assessment of Causality 
For all AEs reported in the eCRF, the investigator will determine a causal relationship to VTP-
850. 
A number of factors will be considered in making this assessment, including: 1) the temporal 
relationship of the event to the administration of VTP-850, 2) whether an alternative aetiology 
has been identified and 3) biological plausibility.  
Causality of all adverse events should be assessed by the investigator using the following 
question: 
“Is there a reasonable possibility that the adverse event may have been caused by VTP-850” 
• 
YES (related): There is a reasonable possibility that VTP-850 contributed to the AE 
• 
NO (not related): There is no reasonable possibility that the AE is causally related to 
the administration of VTP-850. There are other, more likely causes and administration 
of VTP-850 is not suspected to have contributed to the AE 
The investigator is required to provide an assessment of relationship of AEs to VTP-850 or trial 
procedures and determine causality. The sponsor and Medical Monitor can add another causality 
assessment to the investigator’s causality. If the sponsor or the Medical Monitor disagrees with 
the investigator’s causality assessment, the opinion of both the investigator, the sponsor and the 
Medical Monitor should be provided with the report. 
Every effort should be made by the investigator to determine the existence of any pre-existing 
conditions (e.g., headache on trial Day 1 with onset prior to VTP-850 administration) that must 
be taken into consideration when assessing causal relationship of an AE. Pre-existing conditions 
should be recorded in the eCRF as medical history and substantiated by appropriate source 
documentation. Intermittent conditions such as headaches may be present on trial Day 1 but may 

 
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represent an AE if the intensity or duration of the event is worse than usual following trial 
intervention. 
 
Assessment of Outcome 
The outcome of the AE will be assessed as: 
• Recovered/resolved 
• Recovered/resolved with sequelae 
• Not recovered/resolved 
• Unknown 
• Fatal 
• Change in severity 
 
Follow-up of AEs and SAEs 
Treatment of any AEs will be determined by the investigator using their best medical judgment 
and according to current clinical practice guidelines. All applied measures as well as follow-up 
will be recorded in the appropriate eCRF. 
The investigator will continue follow-up on AEs, including laboratory abnormalities, until the 
event has resolved, stabilised, is otherwise explained, the participant completes the trial or is 
lost to follow-up. The resolution date will be recorded on the eCRF as the last date on which the 
participant experienced the AE. If an AE resolution date is uncertain the investigator should 
estimate the completion date based on medical judgment and interview of the participant. 
Approximate dates of resolution from phone or other communications may be taken as AE 
resolution dates. Some examples of estimation of adverse event resolution are: 1) an 
asymptomatic laboratory abnormality on one visit that has not been followed up between visits 
but has resolved by the next visit may be assumed to have resolved by the midpoint of the inter-
visit interval; 2) A resolved AE that was treated may be assumed to have been resolved by the 
end of treatment.  
Adverse events that are still present at the end of the trial should be recorded as ongoing.  
Information recorded on the eCRF must be substantiated in the source documents. If an AE 
evolves into a condition that becomes “serious,” it will be designated as serious on the AE eCRF, 
and a supplemental SAE report form will be completed. 
Follow-up for SAEs will be attempted until resolution or stabilisation and the outcome 
reported to the sponsor, even if this extends beyond the SAE reporting period. 
A3.5. 
REPORTING OF SAES AND/OR AESIS 
All SAEs/AESIs are reported to the sponsor or designee until the end of the trial. Suspected 
unexpected serious adverse reactions are reported even after the trial is over, if the investigator 
becomes aware of them. The trial centre will be provided with specific reporting procedures 
including the SAE/AESI Report form and any supplemental reporting forms to be used. 

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SAEs/AESIs will be reported on the SAE/AESI form and the AE eCRF using a recognised 
medical term or diagnosis that accurately reflects the event. 
SAEs/AESIs will be assessed for severity, causal relationship to VTP-850 or alternative 
aetiology by the sponsor and investigator. The onset and resolution dates of the event and 
medical care taken in response to the event will be documented. If the event has not resolved by 
the end of the trial, it will be documented as “ongoing” on the eCRF, however, follow-up of the 
SAE/AESIs should be attempted until resolved or the condition has stabilised. Information 
recorded on the eCRF must be substantiated in the source documents. 
The SAE form should be completed with all information known at the time and reported per the 
SAE/AESIs reporting guidelines. 
Likewise, fatal or life-threatening SAEs will have to be reported per the SAE reporting 
guidelines. If the Medical Monitor is required by the protocol or chooses to suspend enrolment, 
they shall immediately create a written memorandum for record to the trial file and 
telephonically notify the sponsor of this act. 
Contact information for all safety personnel is contained in the Team Contact List, which will 
be stored at the trial centre in the Investigator Site File and maintained by the trial sponsor. 
Investigators must not wait to collect additional information to fully document the event before 
notifying the Medical Monitor of an SAE/AESI. The initial notification should include the 
following (at a minimum):  
• Protocol number and name and contact number of the investigator 
• Participant identification 
• Investigational product 
• Event term 
 
All SAEs/AESIs must be recorded on the SAE/AESI Report Form and sent to 
 
via email 
within 24 hours of awareness.  Additionally, the 
investigator must submit any updated SAE data to Precision Safety within 24 hours of 
awareness.   
 
Initial notification via telephone or email does not replace the need for the Investigator to 
complete, sign, and return the SAE/AESI report form within the designated reporting time 
frames. 
 
 

 
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 Appendix 4: Contraceptive and Barrier Guidance 
Participants should refrain from donating sperm during the trial for at least 65 days after the last 
dose of VTP-850 
PLUS, either 
• 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent 
OR 
• 
Agree to use a male condom when having sexual intercourse with a woman of childbearing 
potential, and should also be advised of the benefit for a female partner to use a highly 
effective method of contraception as a condom may break or leak 
 
 

 
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 Appendix 5: Abbreviations and Definitions 
List of Abbreviations  
ABBREVIATION 
DEFINITION 
ADT 
androgen deprivation therapy 
AE 
adverse event 
AESI 
Adverse event of special interest 
BRCA 
BReast CAncer gene 
ChAdOx1 
chimpanzee adenovirus Oxford 1 
CI 
confidence interval 
CRP 
C-reactive protein 
CRS 
cytokine release syndrome 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CNS 
Central Nervous System 
DLT 
dose limiting toxicity 
eCRF 
electronic case report form 
ELISpot 
enzyme linked immunospot assay 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
IEC 
independent ethics committee 
IM 
intramuscular(ly) 
IRB 
institutional review board 
IV 
intravenous(ly) 
MedDRA 
The Medical Dictionary for Regulatory Activities 
MFS 
metastasis-free survival 
MRI 
magnetic resonance imaging 
MVA 
Modified Vaccinia virus Ankara 
MVA-BN 
Modified Vaccinia Ankara-Bavarian Nordic 
PAP 
prostatic acid phosphatase 
PBMC 
peripheral blood mononuclear cells 
PCWG3 
Prostate Cancer Working Group 3 
PET 
positron emission tomography 
pfu 
plaque forming units 
PSA 
prostate-specific antigen 
PSMA 
prostate specific membrane antigen 
PT 
preferred term 
RECIST 
Response Evaluation Criteria in Solid Tumours 
RP2R 
recommended Phase 2 regimen 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SI 
International System of Units 
SMC 
Safety Monitoring Committee 
SoA 
Schedule of Assessments 

 
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ABBREVIATION 
DEFINITION 
SOC 
system organ class 
STEAP1 
six-transmembrane epithelial antigen of prostate 1 
TTM 
Time to Metastases 
ULN 
upper limit of normal 
vp 
viral particles 
XRT 
external radiation therapy 
 
List of Definitions  
TERM 
DEFINITION 
Enrolment 
The point at which a participant has met all entry criteria and is 
eligible for dosing.  
VTP-850 
A prime-boost immunotherapeutic regimen consisting of 2 viral 
vectored components, ChAdOx1-PCAQ and MVA-PCAQ 
 
 
 

 
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 Appendix 6: Changes made in Protocol Amendment 
This is Version 5.0 of the protocol. The original protocol (Version 1.0) was issued on 
22 April 2022, Version 2.0 was issued on 01 July 2022, Version 3.0 was issued on 
06 December 2022 and Version 4.0 was issued on 04 March 2024. 
Summary of changes: 
Version 5.0 18 April 2024 
Summary and Justification of Change 
The following changes were made in response to the request from the US Central IRB to 
minimise potential cardiac risks for trial participants: 
• Schedule of Assessments: addition of screening echocardiogram. A historic 
echocardiogram can be used if performed within 3 months of the first dose of 
VTP-850 
• Table 3 Section 2.3.1: addition of echocardiogram in the cardiac risk statement 
• Addition of Section 8.4.5: echocardiogram 
• Section 9.5: included echocardiogram in the assessments that should be 
performed in the event of a cardiac-related event 
Version 4.0 04 March 2024 
Summary and Justification of Change 
The following changes were made to increase participant safety, to minimise potential 
cardiac risks and to monitor cardiac status subsequent to safety review: 
Cardiac safety: 
• Inclusion criterion 11: addition of inclusion criteria regarding troponin T and 
HbA1c 
• Exclusion criterion 12: increased exclusion of prior ADT from within 6 months 
prior to Day1 to outside of the primary prostate cancer therapy 
• Exclusion criterion 13: clarification that of the exclusion of receipt of 
experimental agents for prostate cancer includes participation in any clinical trials 
for prostate cancer with the exception of as being part of primary treatment 
options 
• Exclusion Criterion 19: addition of exclusion of participation in prior clinical trials 
to include previous participating in any clinical trials for prostate cancer with the 
exception of those as part of the primary treatment 
• Addition of exclusion criterion 20 detailing exclusionary cardiovascular conditions 
• Addition of exclusion criterion 21 detailing exclusionary ECG findings 
• Addition of exclusion criterion 22 specifying exclusion of uncontrolled 
hypertension 

 
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• Schedule of Assessments: Addition of on trial monitoring of ECGs 
• Schedule of Assessment and Appendix 2: addition of troponin T and CRP analysis 
• Schedule of Assessments, Section 9 (including addition of Section 9.5) and 
Appendix 3: Addition of classifying cardiac events as AESI and associated 
reporting 
• Table 3 Section 2.3.1: Addition of cardiac risk statement 
• Section 8.4.2: Addition that investigators should pay special attention to any 
symptoms or signs potentially pertaining to cardiotoxicity 
• Section 8.4.3 and Appendix 2: clarification that Troponin T samples will be 
analysed in local laboratories 
 
Other safety parameters: 
• 
Addition of monitoring of anti-antigen antibodies 
The following changes were made to increase homogeneity of participants and data 
collection: 
Clarification of prostate cancer history: 
• 
Inc 4 addition of "or systemic therapy for prostate cancer" 
• 
Inc 6 addition of "and no evidence of prostatic bed recurrence" 
 
Data consistency: 
• 
Inc 6 removal of " An existing PSMA=PET scan showing no metastatic lesions may 
be used instead to confirm M0 status" 
• 
Addition of a PSA collection at Day 91 
• 
Section 4.1: addition that a total of 6 participants in each of cohorts 2 and 3 will 
be required to be dosed with MVA-PCAQ on Day 29 and Day 57 so participants 
whose dosing was delayed will be replaced (unless dosing not to be completed 
for pause of stopping rule criteria being met) 
• 
Section 6.12: addition to detail how recommencement of dosing for participants 
whose dosing was delayed in Phase 1 due to a study pause will be managed 
Clarification of the requirement to qualify sites for the collection of PBMCs as part of 
exploratory analyses: 
• The collection of PBMC samples has changed from being required for all 
participants to only required at those sites that are qualified by Barinthus 
Biotherapeutics to process PBMC samples 
The following changes were made for clarification: 
• 
Exclusion criterion 4: clarification that history of Hep C infection is not 
exclusionary but in line with Ex 10 active Hepatitis C infection is exclusionary. 
• 
Exclusion criterion 10: Updated to clarity that only active hepatitis C virus 
infection is exclusionary 
• 
Update to SoA and associated footnotes following additional assessments 

 
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• 
Secondary Endpoint: rewording of endpoint regarding PSA response to ensure 
clarity 
• 
Exploratory endpoint: moving "other immune responses" from the objective 
around PSA response to the objective around immunogenicity. 
• 
Section 4.1 and Synopsis: clarification of the situation around when a participant 
could be offered an additional dose of MVA-PCAQ 
• 
Section 4.1.2: clarification that if 3 or fewer of the 25 participants at the RP2R in 
Phase 1/ Phase 2 Stage 1 have a PSA response then no further participants will be 
enrolled in the trial 
• 
Section 4.1.4: clarification that if a participant does not have a PSA response by 
their Month 6 visit they will not enter the Long-term Follow-up Period of the trial 
• 
Section 4.1.7: clarification of how any additional MVA-PCAQ doses will be 
managed. 
• 
Section 6.10: clarification that systemic treatment with corticosteroids or other 
immunosuppressive medications within 14 days of the first dose of VTP-850 are 
exclusionary. 
• 
Section 7.2: clarification that disease management for example in the case of 
rapid PSA progression is a reason that the participant may need to discontinue 
from the trial to consider other treatment options. 
• 
Section 8.2.2 clarification that participants with evidence of prostatic bed 
recurrence will be excluded from trial participation  
• 
Section 8.3.2: clarification that biomarker samples will only be analysed after 
Phase 2 Stage 2 is opened.  If Phase 2 Stage 2 is not opened then biomarker 
sample analysis may not be performed. 
• 
Section 9.3: correction of "investigator safety report" to "individual case safety 
report" in bullets 3 and 4 
• 
Section 11: minor updates to enhance clarity 
• 
Section 11.3: addition of statement documenting the review of data of the 25 
participants receiving RP2P to determine whether Phase 2 Stage 2 will be 
opened. 
• 
Appendix 5: updated to include new abbreviations 
• 
Administrative amendments to ensure internal consistency and correct 
typographical errors 
In addition, Vaccitech (UK) Limited changed its name to Barinthus Biotherapeutics (UK) 
Limited on 06 November 2023. Consequent updates have also been made. 
 
Version 3.0, 06 December 2022 
Summary and Justification of Change 
The following changes and clarification were made in response to FDA requests: 

 
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Addition of assessment of TTM in the subset of participants with PSA response to the 
secondary objectives and endpoints 
Addition of assessment of MFS and TTM as exploratory objectives and endpoints 
• 
Revision of DLT criteria 
• 
Clarification of the staggering of enrolment during Phase 1 
Following feedback on current treatment paradigms in this population inclusion criterion 
7 was amended so that participants who had prior prostatectomy should have a Serum 
PSA of >0.3 ng/mL at screening 
Administrative amendments to ensure internal consistency and correct typographical 
errors 
 
Version 2.0, 01 July 2022 
Summary and Justification of Change 
Changes were made to: 
• Amend inclusion criterion 3 to include participants that had undergone primary therapy 
for prostate cancer with brachytherapy. 
• Amend inclusion criterion 7 to document that participants that had prior brachytherapy 
should have a serum PSA of 2ng/mL above nadir. 
• Section 4.1.1 to reorder and slightly reword DLT criteria to improve clarity 
• Include Investigator Agreement within the protocol 
Remove previous legal registered address of sponsor (current legal address was already 
listed) 
Section 8.3.1 included statement that left over immunology blood samples may, with 
participant consent, be retained for future research related to ChAdOx1-PCAQ and 
MVA-PCAQ, confirming that this additional consent is optional, will not be required for 
participation in the trial and may be withdrawn at any time. 
Clarified that SMC will also contain a prostate cancer physician who is not participating in 
the trial 
• Add summary of changes Appendix 6 
Administrative amendments to ensure internal consistency and correct typographical 
errors