Clinical trial NCT04382898
Conditions: Prostate Cancer
Keywords: Prostate cancer PRO-MERIT Cancer vaccine W_pro1 BioNTech SE RNA mCRPC LPC Cemiplimab BNT112
Sponsor: BioNTech SE
Start date: 2019-12-19; Completion date: 2024-01-23
Enrollment: 75 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Open-label, multicenter, dose titration and four-arm expansion trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of BNT112 cancer vaccine (BNT112) monotherapy or in combination with cemiplimab in patients with metastatic castration resistant prostate cancer (mCRPC: Part 1 and Part 2 Arms 1A and 1B) and in patients with high-risk, localized prostate cancer (LPC).

As of February 2023, the trial only recruited LPC patients and no longer mCRPC patients.

Detailed description:
* BNT112 consisted of messenger ribonucleic acid (mRNA \[or RNA\]) targeting 5 antigens expressed in de novo and metastatic prostate cancer that were separately complexed with liposomes to form serum-stable RNA lipoplexes (RNA-LPX).
* The RNA molecules were immune-pharmacologically optimized for high stability, translational efficiency and presentation on major histocompatibility complex (MHC) class I and II molecules. The vaccine was intended for intravenous (IV) bolus injection.
* The RNA-LPX cancer vaccine induced activation of both the adaptive immune system (vaccine antigen-specific CD8+/CD4+ T cell) as well as the innate immune system (TLR7 agonism of single-stranded RNA). The physiology of efficient induction, expansion and differentiation of antigen-specific T cells was associated with programmed death receptor-1 (PD-1) upregulation on these T cells. Thus, the cancer vaccine was expected to have a synergistic mechanism of action with anti-PD-1.
* The step-up dose titration approach allowed for optimal dose management on an individual basis and accounted for inter- and intra-individual variability of the immune system.
* In summary, the mechanism of action of BNT112 both in monotherapy and in combination with anti-PD-1 immune checkpoint inhibitor cemiplimab, together with carefully selected and refined clinical setting presented a unique opportunity for patients with different stages of prostate cancer.

Arms: arm 1: BNT112 monotherapy

Enrollment into this arm is completed. arm 2: BNT112 in combination with cemiplimab

Enrollment into this arm is completed. arm 3: BNT112 monotherapy

Enrollment into this arm is completed. arm 4: BNT112 in combination with cemiplimab arm 5: BNT112 monotherapy arm 6: Following progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with cemiplimab monotherapy

Enrollment into this arm is completed.
Interventions: intervention 1: BNT112 intervention 2: Cemiplimab
Intervention descriptions: intervention 1: Intravenous bolus injection intervention 2: Intravenous infusion

Protocol documents:
Prot_000.pdf: 
BioNTech SE 
Protocol number: RN5609C00 version 6.0 
CONFIDENTIAL 
Page 1 of 122
 
 
CLINICAL TRIAL PROTOCOL 
First-in-human, dose titration and expansion trial to evaluate safety, 
immunogenicity and preliminary efficacy of W_pro1 (BNT112) monotherapy 
and in combination with cemiplimab in patients with prostate cancer 
 
Protocol Number: 
RN5609C00 
Protocol Version: 
6.0 
Including Amendments: 
1 to 5 
Short Title / Acronym: 
PRO-MERIT (Prostate Cancer Messenger RNA 
Immunotherapy) 
Trial Phase: 
1/2A 
Compounds: 
BNT112, cemiplimab 
Sponsor: 
BioNTech SE 
An der Goldgrube 12, 
55131 Mainz, 
Germany 
Clinical Research Organization: 
Syneos Health 
1030 Sync Street, 
Morrisville, NC 27560,  
USA 
Coordinating Investigator: 
Dr. Mark Linch FRCP PhD 
University College London Cancer Institute 
72 Huntley Street, London, United Kingdom 
Regulatory Agency Identifier 
Number(s): 
EudraCT: 2018-004321-86; NCT04382898; 
IND: 26912 
Approval Date: 
23 FEB 2022 
 
The information in this document is confidential and is proprietary to BioNTech SE. It is understood that 
information in this document shall not be disclosed to any third party, in any form, without prior written consent of 
an authorized officer of BioNTech SE. 


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Statement of Compliance 
GCP Compliance 
This trial will be conducted in compliance with the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical 
Practice (ICH) E6(R2), and applicable regulatory requirements. 
Confidentiality Statement 
The information in this document contains trade secrets and commercial information that are 
privileged or confidential and may not be disclosed unless such disclosure is required by 
applicable law or regulations. In any event, persons to whom the information is disclosed must 
be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you 
that is indicated as privileged or confidential. 
 
 


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Sponsor Signatory 
 
 
Özlem Türeci, MD  
Chief Medical Officer 
Telephone: 
+49 (0) 6131 9084 0   
Telefax: 
+49 (0) 6131 9084 39 2010 
E-Mail:  
 
 
Date 
 
 
PPD


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Protocol Amendment Summary of Changes 
 
DOCUMENT HISTORY 
Document 
Date 
Amendment 5 
23 FEB 2022 
Amendment 4_USA 
06 APR 2021 
Amendment 4_DEU 
06 APR 2021 
Amendment 4 
06 APR 2021 
Amendment 3.2 
04 NOV 2020 
Amendment 3.1 
01 OCT 2020 
Amendment 3 
01 OCT 2020 
Amendment 2 
05 MAR 2020 
Amendment 1 
12 SEP 2019 
Original Protocol 
05 MAR 2019 
 
Changes made to the protocol using the protocol amendments are described in detail in the 
document Protocol Amendment History which is available upon request. This Protocol 
Amendment History is filed together with the protocol in the trial master file. A short description 
of the changes made in each amendment are listed below. 
Amendment 1 (12 SEP 2019) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
A new protocol template was implemented, and inconsistencies in the previous protocol version 
were corrected.  
Amendment 2 (05 MAR 2020) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.  
Overall Rationale for the Amendment: 
The dose-limiting toxicity section was updated, and inconsistencies in the previous protocol 
version were corrected.  


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Amendment 3 (01 OCT 2020) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
Amendment 3 implemented primarily cemiplimab-relevant information and changes reflecting 
feedback from the pre-IND meeting with the US Food and Drug Administration (FDA) 
regarding the newly diagnosed localized prostate cancer clinical setting. The company product 
code BNT112 for BNT112 cancer vaccine was introduced. Also, information relevant to Part 2 
was corrected and actualized including the dose range confirmation. 
Amendment 3.1 (01 OCT 2020) – Local amendment for Germany 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.  
Overall Rationale for the Amendment:  
Amendment 3.1 incorporated an additional exclusion criterion to the trial protocol in regards to 
mentally incapacitated patients, as requested by German authorities. 
Amendment 3.2 (04 NOV 2020) – Local amendment for the United States 
Overall Rationale for the Amendment:  
Amendment 3.2 incorporated an additional exclusion criterion to the trial protocol in regards to 
mentally incapacitated patients, as requested by the United States authorities. 
Amendment 4 (06 APR 2021) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
Amendment 4 implemented the option for patients with mCRPC on BNT112 monotherapy to 
switch to cemiplimab monotherapy after disease progression. Additional changes were 
incorporated following regulatory agency feedback. 
Amendment 4_DEU (06 APR 2021) – Local amendment for Germany 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
Amendment 4_DEU incorporated an additional exclusion criterion to the amended global 
protocol (v5.0) in regards to mentally incapacitated patients, as previously requested by German 
authorities. 
Amendment 4_USA (06 APR 2021) – Local amendment for the United States 
Overall Rationale for the Amendment: 
Amendment 4_USA incorporated an additional exclusion criterion to the amended global 
protocol (v5.0) in regards to mentally incapacitated patients, as previously requested by the 
United States authorities. 


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Amendment 5 (23 FEB 2022) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
Amendment 5 included the following substantial changes: 
• Change of the immunogenicity secondary endpoint to an exploratory endpoint. 
- 
Immunogenicity assessments, within the context of the PRO-MERIT trial, support 
the generation of a hypothesis to investigate if there will be induction/expansion of 
vaccine antigen-specific T cells following treatment with BNT112 (W_pro1). The 
importance of induction of immunogenicity for the assessment of safety and 
preliminary clinical activity is not proven, which justifies re-classification of this 
endpoint. 
• Additional exclusion criterion regarding mentally incapacitated patients, as previously 
requested by the United States and German authorities. 
• The Schedule of Assessments was adapted to allow for additional blood draws at C1D8, 
C1D15, C2D8, and C2D15 for prostate-specific antigen level assessment. 
- 
This change is considered substantial as it affects one of the secondary objectives to 
evaluate anti-tumor activity based on levels of PSA and diagnostic or medical 
monitoring procedures. This change is likely to positively impact the scientific value 
of the trial as it may facilitate a deeper understanding of the pharmacological effects 
induced at the early stages of trial treatment. 
Other changes included a terminology change from W_pro1 to BNT112 and the correction of 
inconsistencies. 
 


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Table of Contents 
 
Statement of Compliance ..............................................................................................................2 
Sponsor Signatory ..........................................................................................................................3 
Protocol Amendment Summary of Changes ...............................................................................4 
Table of Contents ...........................................................................................................................7 
List of In-Text Tables ....................................................................................................................9 
List of In-Text Figures ...................................................................................................................9 
1. 
Protocol Summary ........................................................................................................10 
1.1. 
Synopsis ..........................................................................................................................10 
1.2. 
Schema ............................................................................................................................25 
1.3. 
Schedule of Activities: Part 1 and Part 2 Arms 1A and 1B ............................................27 
1.4. 
Schedule of Activities: Part 2 Arms 2 and 3 ...................................................................30 
1.5. 
Schedule of Activities: Part 2 Arm 1B – Optional Cemiplimab 
Treatment Following Progression after BNT112 Monotherapy .....................................33 
2. 
Introduction ...................................................................................................................36 
2.1. 
Background .....................................................................................................................36 
2.2. 
Trial Rationale ................................................................................................................39 
2.3. 
Benefit/Risk Assessment ................................................................................................41 
3. 
Objectives and Endpoints ............................................................................................43 
4. 
Trial Design ...................................................................................................................46 
4.1. 
Overall Design ................................................................................................................46 
4.2. 
Planned Number of Patients ...........................................................................................49 
4.3. 
Trial Design Rationale ....................................................................................................49 
4.4. 
Dose and Schedule Rationale .........................................................................................51 
4.5. 
End of Trial Definition ...................................................................................................52 
5. 
Trial Population ............................................................................................................52 
5.1. 
Inclusion Criteria ............................................................................................................52 
5.2. 
Exclusion Criteria ...........................................................................................................55 
5.3. 
Screen Failures ................................................................................................................58 
6. 
Trial Treatment.............................................................................................................59 
6.1. 
Trial Treatments Administered .......................................................................................62 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................64 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................64 
6.4. 
Trial Treatment Compliance ...........................................................................................64 
6.5. 
Concomitant Therapy .....................................................................................................65 
6.6. 
Dose Modifications .........................................................................................................67 
6.7. 
Treatment After the End of the Trial ..............................................................................71 


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7. 
Discontinuation of Trial Treatment and Patient 
Discontinuation/Withdrawal........................................................................................71 
7.1. 
Discontinuation of Trial Treatment ................................................................................71 
7.2. 
Patient Discontinuation/Withdrawal from the Trial .......................................................72 
7.3. 
Lost to Follow-up............................................................................................................72 
8. 
Trial Assessments and Procedures ..............................................................................72 
8.1. 
Efficacy Assessments .....................................................................................................73 
8.2. 
Safety Assessments .........................................................................................................75 
8.3. 
Other Assessments ..........................................................................................................77 
8.4. 
AEs and SAEs .................................................................................................................77 
8.5. 
Treatment of Overdose ...................................................................................................80 
8.6. 
Pharmacokinetics ............................................................................................................80 
8.7. 
Pharmacodynamics .........................................................................................................80 
8.8. 
Biomarkers ......................................................................................................................81 
8.9. 
Immunogenicity Assessments.........................................................................................82 
9. 
Statistical Considerations .............................................................................................82 
9.1. 
Statistical Hypotheses .....................................................................................................82 
9.2. 
Sample Size Determination ............................................................................................82 
9.3. 
Analyses Sets ..................................................................................................................83 
9.4. 
Statistical Analyses .........................................................................................................84 
9.5. 
Interim and Final Analyses .............................................................................................88 
9.6. 
Data Monitoring Committee/Safety Review Committee................................................88 
10. 
Supporting Documentation and Operational Considerations ..................................89 
10.1. 
Appendix 1: Regulatory, Ethical, and Trial Oversight 
Considerations ................................................................................................................89 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................94 
10.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................95 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information .................................................................................................109 
10.5. 
Appendix 5: Declaration of Helsinki ............................................................................110 
10.6. 
Appendix 6: ECOG PS .................................................................................................111 
10.7. 
Appendix 7: Graphical Illustration of PSA Progression for Trial 
Eligibility ......................................................................................................................112 
10.8. 
Appendix 8: Consensus Grading for Cytokine Release Syndrome ..............................112 
10.9. 
Appendix 9: Criteria for Disease Response Assessment ..............................................113 
10.10. 
Appendix 10: Abbreviations .........................................................................................115 
10.11. 
Appendix 11: Protocol Amendment History ................................................................119 
11. 
References ....................................................................................................................119 
 
 


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List of In-Text Tables 
Table 3-1: 
Objectives and endpoints of the clinical trial .................................................... 43 
Table 4-1: 
Dose Titration Scenarios and Rules .................................................................. 48 
Table 6-1: 
Identity and Properties of IMP1: BNT112 (IMP) ............................................. 62 
Table 6-2: 
Identity and Properties of IMP2: Cemiplimab .................................................. 63 
Table 6-3: 
Identity and Properties of NIMP: Goserelin Acetate ........................................ 63 
Table 10-1: 
Local Safety Laboratory Tests (Blood and Urine) - Overview ......................... 94 
Table 10-2: 
Central Blood Biomarker Assessment - Overview ........................................... 94 
Table 10-3: 
Highly Effective Methods of Contraception ................................................... 109 
Table 10-4: 
ECOG PS ......................................................................................................... 111 
Table 10-5: 
ASTCT CRS Consensus grading .................................................................... 112 
 
List of In-Text Figures 
Figure 1-1: 
Trial Design ....................................................................................................... 25 
Figure 1-2: 
Treatment Administration – Part 1 and Part 2 ................................................... 26 
Figure 6-1: 
Treatment Administration – Part 1 and Part 2 ................................................... 61 
Figure 6-2: 
Handling of TEAEs fulfilling the DLT criteria ................................................. 69 
Figure 10-1: 
Graphical Illustration of PSA Progression for Trial Eligibility ...................... 112 
 


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1. 
Protocol Summary 
1.1. 
Synopsis 
Title: 
First-in-human, dose titration and expansion trial to evaluate safety, 
immunogenicity and preliminary efficacy of W_pro1 (BNT112) monotherapy 
and in combination with cemiplimab in patients with prostate cancer 
Acronym: 
PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy) 
Sponsor’s trial no.: 
RN5609C00 
EudraCT no.: 
2018-004321-86 
Clinical development: Phase 1/2A 
Trial design: 
Open-label, multicenter, dose titration and expansion four-arm trial to 
evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of 
BNT112 cancer vaccine (BNT112) monotherapy or in combination with 
cemiplimab in patients with metastatic castration-resistant prostate cancer 
(mCRPC: Part 1 and Part 2 Arms 1A and 1B) and in patients with high-risk, 
localized prostate cancer (LPC) eligible for treatment with androgen-
deprivation therapy (ADT) followed by radical prostatectomy (LPC: Part 2 
Arms 2 and 3) 
Trial centers and 
investigators: 
Approximately 30 investigational sites (trial centers)  
Countries: 
Up to 5 countries  
Trial objectives and endpoints: 
 
OBJECTIVES 
ENDPOINTS 
PRIMARY OBJECTIVE 
PRIMARY ENDPOINTS 
• 
(Part 1 and Part 2) Assess safety 
and tolerability profile of 
BNT112 monotherapy or in 
combination with cemiplimab 
• 
Occurrence of dose-limiting toxicities (DLTs). 
• 
Occurrence of treatment-emergent adverse events 
(TEAEs) reported by relationship, grade, and 
seriousness according to National Cancer Institute 
(NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0. 
• 
(Part 2 Arms 1a and 1b) 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy and in 
combination with cemiplimab in 
patients with mCRPC based on 
objective response rate (ORR) 
• 
ORR, defined as the number of patients with a 
complete response (CR) or partial response (PR) per 
Prostate Cancer Working Group 3 (PCWG3) as 
determined by the investigator as best objective 
response divided by the number of patients in the 
analysis set. 


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OBJECTIVES 
ENDPOINTS 
SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
• 
Evaluate anti-tumor activity 
based on levels of prostate-
specific antigen (PSA) 
• 
PSA decline of 0 to 25%, >25% to 50%, and >50% 
compared to baseline. 
• 
PSA doubling time (PSADT) post-treatment on C4D1 
and D1 of every fourth subsequent cycle (e.g., C8D1, 
C12D1, etc.) in Part 1 and Part 2 Arms 1A and 1B, or 
on C4D1, C8D1, and end of treatment (EoT) in Part 2 
Arms 2 and 3 compared to baseline. 
• 
PSA decline of ≥50% (according to the PCWG3). 
• 
(Part 1) Evaluate preliminary 
anti-tumor activity of BNT112 
monotherapy in patients with 
mCRPC based on ORR 
• 
ORR, defined as the number of patients with a CR or 
PR per PCWG3 as determined by the investigator as 
best objective response divided by the number of 
patients in the analysis set. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy or in combination 
with cemiplimab in patients with 
newly diagnosed LPC 
• 
Tumor response post-treatment compared to baseline. 
EXPLORATORY OBJECTIVES 
EXPLORATORY ENDPOINTS 
• 
Determine systemic 
induction/expansion of BNT112 
antigen-specific T cells for 
BNT112 monotherapy or in 
combination with cemiplimab 
• 
Occurrence of de novo induction or increase of 
BNT112 antigen-specific T cells in peripheral blood 
under treatment on Cycle 3 Day 15 (C3D15), and/or 
C8D15, EoT, or safety follow-up compared to baseline. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy and in combination 
with cemiplimab in patients with 
mCRPC 
• 
Duration of response (DoR), defined as the time from 
the first occurrence of a documented OR to the time of 
the first disease progression per PCWG3, as determined 
by the investigator, or death from any cause, whichever 
occurs first. 
• 
ORR and DoR, defined as above, using immune-
modified Response Evaluation Criteria in Solid Tumors 
(iRECIST).  
• 
Progression-free survival (PFS), defined as the time 
from the first trial treatment to the first disease 
progression per PCWG3 as determined by the 
investigator, and per iRECIST determined by central 
reading, or death from any cause, whichever occurs 
first. 
• 
Overall survival (OS), defined as the time from first 
trial treatment until death from any cause. 
• 
Number of cycles received and relative dose intensity 
(RDI). 


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OBJECTIVES 
ENDPOINTS 
• 
Evaluate preliminary anti-tumor 
activity of cemiplimab in 
patients with mCRPC who have 
been previously treated with, and 
who have progressed after 
BNT112 monotherapy 
• 
ORR, defined as the number of patients with a CR or 
PR per PCWG3 as determined by the investigator as 
best objective response (OR) divided by the number of 
patients in the analysis set. 
• 
DoR, defined as the time from the first occurrence of a 
documented OR to the time of the first disease 
progression per PCWG3, as determined by the 
investigator, or death from any cause, whichever occurs 
first. 
• 
ORR and DoR, defined as above, using iRECIST.  
• 
PFS, defined as the time from the first cemiplimab 
treatment to the first disease progression per PCWG3 as 
determined by the investigator, and per iRECIST 
determined by central reading, or death from any cause, 
whichever occurs first. 
• 
PFS2, defined as the time from the first trial treatment 
to the first disease progression after start of cemiplimab 
per PCWG3 as determined by the investigator, or death 
from any cause, whichever occurs first. 
• 
OS, defined as the time from first trial treatment until 
death from any cause. 
• 
Number of cycles received and RDI. 
• 
Assess safety and tolerability 
profile of cemiplimab 
monotherapy in patients 
following progression after 
BNT112 monotherapy 
• 
Occurrence of TEAEs reported by relationship, grade, 
and seriousness according to NCI CTCAE v5.0. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 monotherapy 
or in combination with 
cemiplimab in patients with 
newly diagnosed LPC  
• 
PFS, defined as the time from the first trial treatment to 
the first disease progression per PCWG3 as determined 
by the investigator, or death from any cause, whichever 
occurs first. 
• 
OS, defined as the time from first trial treatment until 
death from any cause. 
• 
Preliminary assessment of 
biomarkers that might act as 
potential predictive, 
pharmacodynamics, anti-tumor, 
and safety indicators of activity 
of BNT112 monotherapy or in 
combination with cemiplimab  
• 
Status of tumor mutational burden and immune-related 
gene expression (at the ribonucleic acid [RNA] level) in 
tumor tissue prior to treatment. 
• 
Change in protein expression pattern/levels of tumor 
microenvironment markers (e.g., CD3, CD8, MHC-I, 
PD-L1, etc.) and prostate tumor markers (e.g., PSA, 
PSAP, NKX3-1, etc.) in tumor tissue post-treatment 
compared to baseline. 


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OBJECTIVES 
ENDPOINTS 
• 
Baseline status or change in RNA target expression of 
BNT112–encoded antigens in the post-treatment tissue 
compared to baseline.  
• 
Change in T cell clonality/diversity post-treatment 
compared to baseline. 
• 
Changes in blood biomarkers prior to and during trial 
treatment. 
Abbreviations: C = cycle; CR = complete response; CTCAE v5.0 = Common Terminology Criteria for Adverse 
Events, version 5.0; D = day of cycle; DLT = dose-limiting toxicity; DoR = duration of response; EoT = end of 
treatment; iRECIST = immune-modified Response Evaluation Criteria in Solid Tumors; MHC = major 
histocompatibility complex; NCI = National Cancer Institute; NKX3-1 = NK3 homeobox 1; OR = objective 
response; ORR = objective response rate; OS = overall survival; PCWG3 = Prostate Cancer Working Group 3; PD-
L1 = programmed cell death 1 ligand 1; PFS = progression-free survival; PR = partial response; PSA = prostate-
specific antigen; PSADT = prostate-specific antigen doubling time; PSAP = prostate-specific acid phosphatase; RDI 
= relative dose intensity; TEAE = treatment-emergent adverse event. 
 
Investigational medicinal products (IMPs): 
IMP 1: 
BNT112 (previously referred to as W_pro1 in this and other trial-related 
documentation) 
Composition: 
BNT112 consists of messenger RNA (mRNA; further referred to as RNA) 
targeting 5 antigens expressed in de novo and metastatic prostate cancer that 
are separately complexed with liposomes to form serum-stable 
RNA lipoplexes 
Administration: 
Five slow intravenous (IV) bolus injections per administration (i.e., one 
injection per each antigen followed by a saline flush and separated from the 
next injection by at least 5 minutes) 
Dosage regimen: 
One cycle (C) is defined as 21 days 
The patients will receive the following treatments in the following dose and 
schedule:  
Part 1 and Part 2 Arms 1A and 1B (mCRPC) 
• 
IV administration of BNT112 on Day (D)1/8/15 of C1 (intra-patient 
dose titration) and C2, thereafter starting with D1 of C3 every 3 weeks 
(Q3W) until the EoT criterion is met 
• 
Part 1/Dose Titration 
- 
Three doses of BNT112 will be used for an intra-patient dose 
titration during C1:
µg,
µg, and 
µg of total RNA, 
comprising
µg, 
µg, and 
µg of RNA of each of the 
5 antigens encoded by BNT112, respectively 
• 
Part 2/Expansion 
- 
Recommended expansion dose range (REDR) was selected 
after the review of individual and cumulative safety data, and 
CCI
CCI
CCI
CCI
CCI
CCI


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preliminary pharmacodynamic data of Part 1 by the Safety 
Review Committee (SRC). The selected dose range consists of 
a starting first dose of BNT112 of
 µg, with an intra-patient 
dose titration to
µg in the second dose, and 
µg of total 
RNA in the next doses. Total RNA of 
µg,
µg and 
µg 
comprise
µg, 
µg, and 
µg of RNA of each of the 
5 antigens encoded by BNT112, respectively 
- 
Part 2 Arm 1A: Cemiplimab
mg IV Q3W 
- 
Part 2 Arm 1B: Following progression after BNT112 
monotherapy, patients have the option to be treated with 
cemiplimab
mg IV Q3W monotherapy  
Part 2 Arms 2 and 3 (LPC) – Part 2/Expansion ONLY 
• 
IV administration of BNT112 on D1/8/15 of C1 (intra-patient dose 
titration) and C2, thereafter starting with D1 of C3 in a Q3W schedule 
until C8 followed by radical prostatectomy 
• 
Part 2 Arm 2: Cemiplimab
mg IV Q3W 
Duration of 
treatment: 
• 
Part 1 and Part 2 Arms 1A and 1B (mCRPC): The treatment with 
BNT112 will last until unacceptable toxicity or disease progression 
• 
Part 2 Arms 2 and 3 (LPC): The treatment with BNT112, cemiplimab 
will last until unacceptable toxicity or disease progression, or up to C8. 
• 
If either BNT112 or cemiplimab needs to be discontinued, treatment 
with either cemiplimab or BNT112 can continue upon investigator’s 
and sponsor’s agreement 
• 
If treatment with ADT (e.g., goserelin acetate) needs to be 
discontinued, cemiplimab and/or BNT112 also need(s) to be 
discontinued 
IMP 2: 
Cemiplimab (Libtayo) 
Composition: 
Programmed death receptor-1 (PD-1) blocking antibody 
Dosage regimen and 
duration of 
treatment: 
Refer to above description of IMP1 for dosage regimen and duration of 
treatment 
Non-investigational medicinal product (NIMP):  
Part 2 Arms 2 and 3 (LPC) 
ADT, e.g., Goserelin acetate subcutaneous (SC) injection at a dose of 10.8 mg every 12 weeks 
(Q12W) or other ADT according the current prescribing information valid in a given country. 
Product: 
Goserelin acetate (Zoladex® LA 10.8 mg implant) 
Composition: 
Goserelin acetate (equivalent to 10.8 mg goserelin) 
Administration: 
SC 
Dosage regimen: 
One 10.8 mg depot injection given into the anterior abdominal wall Q12W 
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Duration of 
treatment: 
Two injections (≤7 days C1D1 and 12 weeks after the first injection); 
treatment will last until unacceptable toxicity or disease progression, or up to 
C8 
Treatment overview: 
 
 
 
Abbreviations and Footnotes: 
LPC = localized prostate cancer; mCRPC = metastatic castration-resistant prostate cancer; Q3W = every 
three weeks. 
& 
Recommended dose range (REDR) is confirmed in Part 1. 
* 
Maximum administered dose 
µg; minimum administered dose
µg; no dose re-escalation allowed. 
# 
In combination with ADT (e.g., goserelin). 
$ 
From Day 1 of C1 onward, each patient will receive the individual standard dose (or the highest tolerated dose 
from Cycle 1) at each BNT112 administration. 
% 
Following progression after BNT112 monotherapy, patients have the option to be treated with cemiplimab 
monotherapy 
mg IV Q3W. 
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Background 
treatment: 
Not applicable 
Discontinuation-of-
treatment criteria: 
Unacceptable toxicity, evidence of tumor progression, consent withdrawal or 
patient’s withdrawal from the trial at the discretion of the investigator may 
lead to termination of treatment. 
Indication: 
Prostate cancer (adenocarcinoma) 
Number of patients: 
There will be 3 to 9 patients in Part 1 (dose titration part, single arm) and up 
to 106 patients in Part 2 (expansion part, four arms: up to 33 patients in 
Arm 1A and Arm 1B, respectively, and approximately 20 patients in Arm 2 
and Arm 3, respectively). Drop-outs may be replaced. In total, there will be 
approximately 115 patients. 
Diagnosis and main 
criteria for inclusion: 
Each potential participant must fulfill all of the following criteria at screening 
to be enrolled in the trial. In addition, all lab criteria must be fulfilled within 
7 days prior to starting IMP. 
Inclusion criteria for all patients 
1. Patients must be male and aged ≥18 years. 
2. Patients must have histologically confirmed prostate adenocarcinoma. 
3. Patients or their legally authorized representative (if applicable) must sign 
an informed consent form (ICF) indicating that they understand the 
purpose of the procedures required for the trial and are willing to 
participate. 
4. Patients must have an Eastern Cooperative Oncology Group Performance 
Status (ECOG PS) score of 0 or 1.  
5. Patients must have adequate organ and bone marrow function, defined as:  
a. Bone marrow/hematological function:  
- 
Absolute neutrophil count ≥1.5 × 109/L.  
- 
Hemoglobin ≥9.0 g/dL. No transfusion is allowed within 
2 weeks prior to trial treatment initiation.  
- 
Platelet count ≥100 × 109/L. 
b. Coagulation status: 
- 
International normalized ratio ≤1.5 upper limit of normal 
(ULN). Unless on therapeutic anticoagulants with values 
within therapeutic window. 
c. Renal function: 
- 
Glomerular filtration rate ≥45 mL/min/1.73 m² according to the 
abbreviated Modification of Diet in Renal Disease equation. 
6. Patients who are sexually active with a woman of childbearing potential 
must agree to use a condom with spermicidal 
foam/gel/film/cream/suppository in addition to at least one form of highly 
effective contraception used by the patient or their partner during the trial 
starting after signing the ICF and for 90 days after receiving the last dose 
of BNT112 OR for 6 months after receiving the last dose of cemiplimab. 


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7. Patients should not donate sperm during the trial starting after signing the 
ICF and for 90 days after receiving the last dose of BNT112 OR for 
6 months after receiving the last dose of cemiplimab. 
8. Patients must be willing and able to adhere to the prohibitions and 
restrictions specified in this protocol.  
In addition to the above inclusion criteria the following are mandatory for the 
different treatment arms: 
 
Specific inclusion criteria for mCRPC patients (Part 1 and Part 2 
Arms 1A and 1B) 
9. Patients must have histologically confirmed mCRPC and have progressed 
after at least 2 but no more than 3 lines of life-prolonging systemic therapy 
(e.g., abiraterone or enzalutamide, docetaxel, cabazitaxel) or cannot 
tolerate or have refused any of these therapies. These lines of therapy 
include life-prolonging therapies administered in the metastatic hormone–
sensitive setting.  
10. Prior surgical or chemical castration with a serum testosterone 
<1.7 nmol/L (50 ng/dL). If the method of castration is luteinizing 
hormone-releasing hormone analogue (LHRHa), there must be a plan to 
maintain effective LHRHa therapy for the duration of the trial. 
11. Patients must have documented mCRPC progression within 6 months prior 
to screening (assuming no subsequent change in treatments), as 
determined by the investigator, by means of 1 or more of the following 
criteria: 
a. PSA progression as defined by a minimum of 2 rising PSA levels 
with an interval of ≥1 week between each assessment where the 
PSA value at screening should be >2 ng/mL. 
b. Two rises out of 3 PSA sequential tests separated by at least 
1 week also satisfies the criteria for baseline progression providing 
a new nadir is not established (i.e., upward trend). 
c. Radiographic disease progression in soft tissue based on modified 
Response Evaluation Criteria in Solid Tumors, version 1.1 
(RECIST 1.1) with or without PSA progression. 
d. Radiographic disease progression in bone defined as the 
appearance of 2 or more new bone lesions on bone scan with or 
without PSA progression. 
12. Patients must have adequate liver function defined as:  
a. Total bilirubin <1.5 × ULN (≤3 × ULN is acceptable for patients 
with known Gilbert disease). 
b. Aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) ≤2.5 × ULN.  
- 
For patients with hepatic metastases, total bilirubin 
<3 × ULN and AST or ALT <5 × ULN are acceptable. 


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- 
For patients with bone metastases, alkaline phosphatase 
<5 × ULN and albumin ≥2.5 g/dL are acceptable.  
13. Patients must agree to provide an archival pre-treatment formalin-fixed, 
paraffin-embedded tumor sample if available. 
Specific inclusion criteria for newly diagnosed LPC patients (Part 2 
Arms 2 and 3)  
14. Treatment-naïve patients with LPC (i.e., N0, M0). According to risk levels 
of the European Association of Urology Guidelines on Prostate Cancer 
(2018)24, and in line with the U.S. National Comprehensive Cancer 
Network (NCCN 2020)35, patients must have at least 1 of the following: 
a. PSA >20 ng/mL or 
b. Gleason Score >7 or 
c. Localized stage ≥cT2c, N0, M0 according to tumor, node, 
metastasis classification 
15. Patients who intend to have and are suitable for a radical prostatectomy. 
16. Patients must have adequate liver function defined as: 
a. Total bilirubin ≤1.5 × ULN (≤3 × ULN is acceptable for patients 
with known Gilbert disease) 
b. AST and ALT ≤2.5 × ULN 
17. Patients must agree to provide tumor sample(s) from pre-treatment 
diagnostic biopsy and planned post-treatment surgery. 
18. Patient must be eligible for up to 6 months of ADT treatment before 
prostatectomy. 
Diagnosis and main 
criteria for exclusion: Exclusion criteria for all patients 
Medical Conditions  
1. Patients with uncontrolled intercurrent illness, including but not limited 
to: 
a. Ongoing or active infection which requires systemic treatment with 
antibiotics or corticosteroid therapy within 14 days before the first 
dose of IMP. 
b. Symptomatic congestive heart failure (Grade III or IV as classified 
by the New York Heart Association), myocardial infarction within 
3 months before screening, unstable angina pectoris, or cardiac 
arrhythmia. 
c. Known recent history (in the past 5 years) or presence of significant 
pulmonary conditions such as uncontrolled chronic lung disease, or 
any evidence of interstitial lung disease, or active, non-infectious 
pneumonitis. 
d. Uncontrolled hypertension defined as systolic blood pressure 
≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite 
optimal medical management. 


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e. Known primary immunodeficiencies, either cellular (e.g., DiGeorge 
syndrome, T cell negative severe combined immunodeficiency 
[SCID]) or combined T- and B-cell immunodeficiencies (e.g., T- and 
B-cell negative SCID, Wiskott Aldrich syndrome, ataxia 
telangiectasia, common variable immunodeficiency). 
f. Ongoing or recent evidence (within the past year) of significant 
autoimmune disease that required treatment with systemic 
immunosuppressive treatments which may suggest risk for immune-
related adverse events (AE). 
Note: Patients with autoimmune-related hyperthyroidism, 
autoimmune-related hypothyroidism who are in remission, or on a 
stable dose of thyroid-replacement hormone, vitiligo, or psoriasis 
may be included. 
g. Non-healing wound, skin ulcer (of any grade), or bone fracture. 
h. Patients with prior allogeneic stem cell or solid organ 
transplantation. 
i. 
Patients with the following risk factors for bowel perforation (e.g., 
history of acute diverticulitis or intra-abdominal abscess in the last 
3 years; history of gastrointestinal obstruction or abdominal 
carcinomatosis). 
j. 
Patients with uncontrolled type 1 diabetes mellitus. 
Note: Patients controlled on a stable insulin regimen are eligible. 
k. Patients with uncontrolled adrenal insufficiency. 
l. 
Any other disease, metabolic dysfunction, physical examination 
finding, and/or laboratory finding giving reasonable suspicion of a 
disease or condition that contraindicates the use of an investigational 
drug or may render the patient at high-risk for treatment of 
complications. 
2. Patients with a known history or current malignancy other than the 
inclusion diagnosis.  
Note: Exceptions are patients with malignancies with a negligible risk of 
metastasis or death, that have been adequately treated, such as non-
invasive basal cell or non-invasive squamous cell skin carcinoma, non-
invasive, superficial bladder cancer, and any cancer with a CR that lasted 
more than 2 years may be included. 
3. Patients who have had a splenectomy. 
4. Patients who have had major surgery (e.g., requiring general anesthesia) 
within 4 weeks before screening, or have not fully recovered from surgery, 
or have a surgery planned during the time of trial participation, except for 
the radical prostatectomy planned for patients in Part 2 Arms 2 and 3.  
5. Patients who have a known history of any of the following: 
a. HIV 1 or 2 
b. Hepatitis B (carrier or active infection) 


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c. Hepatitis C (unless considered cured 5 years post curative anti-viral 
therapy) 
6. Patients with a known allergy, hypersensitivity, or intolerance to BNT112 
or its excipients (all patients in Parts 1 and 2), cemiplimab or its excipients 
(patients in Part 2 Arm 1A, Arm 1B switch-over patients, and Arm 2 
only), or to ADT (e.g., goserelin) or excipients thereof (patients in Part 2 
Arms 2 and 3 only). 
7. Patients with any condition for which, in the opinion of the investigator, 
participation would not be in the best interest of the patient (e.g., 
compromise the well-being) or that could prevent, limit, or confound the 
protocol-specified assessments. 
8. In situations where trial patients are not legally competent to provide 
consent (e.g., mentally incapacitated), these patients are not allowed to 
enter the trial. 
Prior/Concomitant Therapy 
9. Patients who have received or currently receive the following 
therapy/treatment: 
a. Chronic systemic immunosuppressive corticosteroid treatment 
(prednisone >5 mg daily orally [PO] or IV, or equivalent) during the 
trial.  
Note: Replacement therapy (e.g., physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency) is not 
considered a form of systemic treatment and is permitted. 
b. Prior treatment with other immune-modulating agents that was (a) 
within fewer than 4 weeks (28 days) or 5 half-lives (whichever is 
longer) prior to the first dose of cemiplimab, or (b) associated with 
immune-mediated AEs that were Grade ≥1 within 90 days prior to 
the first dose of cemiplimab, or (c) associated with toxicity that 
resulted in discontinuation of the immune-modulating agent. 
c. Prior treatment with other immune-modulating agents for any non-
cancer disease within 4 weeks or 5 half-lives of the agent (whichever 
is longer) before the first dose of IMP. 
d. Prior treatment with live-attenuated vaccines within 4 weeks before 
the first dose of IMP and during treatment with IMP.  
e. Prior treatment with an investigational drug (including 
investigational vaccines) within 4 weeks or 5 half-lives of the agent 
(whichever is longer) before the planned first dose of IMP.  
f. Therapeutic PO or IV antibiotics within 14 days prior to enrollment.  
Note: Patients receiving prophylactic antibiotics (e.g., for prevention 
of a urinary tract infection or chronic obstructive pulmonary 
disease) may be enrolled. 
g. Concurrent use of herbal products that may decrease PSA levels 
(e.g., saw palmetto). 


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Other exclusion criteria for ALL patients 
10. Patients who have previously been enrolled in this trial. 
11. Patients with substance abuse or known medical, psychological, or social 
conditions that may interfere with the patient’s participation in the trial or 
evaluation of the trial results. 
12. Patients affiliated with the investigational site (e.g., a close relative of the 
investigator or dependent person, such as an employee or student of the 
investigational site) 
Specific exclusion criteria for mCRPC patients (Part 1 and Part 2 Arms 1A 
and 1B) 
Excluded medical conditions  
13. Patients with toxicities from previous anti-cancer therapies that have not 
resolved to baseline levels or to Grade ≤1 according to NCI CTCAE v5.0 
with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, 
hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, 
hypothyroidism, and peripheral neuropathy must have recovered to 
Grade ≤2.  
14. Patients with clinically active brain metastases.  
a. Patients with a history of symptomatic metastatic brain or meningeal 
tumors may be included, if the end of definitive therapy is >3 months 
before the first dose of BNT112 and the patients have no clinical or 
radiological evidence of tumor growth. 
b. Patients with brain metastases must not be undergoing acute or 
chronic corticosteroid therapy or steroid taper.  
c. Patients with central nervous system symptoms should undergo a 
computed tomography (CT) scan or magnetic resonance imaging 
(MRI) of the brain to exclude new or progressive brain metastases. 
Spinal cord metastasis is acceptable. However, patients with spinal 
cord compression should be excluded. 
Excluded prior or concomitant anti-cancer therapies  
15. Patients who have received or currently receive the following anti-cancer 
therapy/agent:  
a. Prior radiation therapy with curative intent within 14 days before the 
first dose of IMP. 
Note: Palliative radiotherapy is allowed. 
b. Prior treatment with an anti-cancer agent (within 4 weeks or for 
systemic therapies after at least 5 half-lives of the drug [whichever is 
longer] before the first dose of IMP). 
Note: Prior treatment with bone resorptive therapy, such as 
bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and 
denosumab, is allowed assuming that the patients have been on 
stable doses for ≥4 weeks prior to first dose of trial treatment. 
c. Prior treatment with anti-cancer immunomodulating agents, such as 
blockers of PD-1, programmed cell death 1 ligand 1 (PD-L1), tumor 


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necrosis factor receptor superfamily member 9 (TNRSF9, 4-1BB, 
CD137), tumor necrosis factor receptor superfamily member 4 
(OX-40), therapeutic vaccines, cytokine treatments, or any 
investigational agent within 4 weeks or 5 half-lives (whichever is 
longer) before the first dose of IMP. 
Specific exclusion criteria for LPC patients (Part 2 Arms 2 and 3) 
16. Patients who are expected to be unable to undergo an mpMRI or MRI. 
Coordinating 
investigator: 
Dr. Mark Linch FRCP PhD, Consultant Medical Oncologist UCL-Cancer 
Institute, London, United Kingdom. 
Methodology: 
The trial consists of 2 parts: Part 1 – dose titration and Part 2 – expansion with 
four arms: Arms 1A and 1B (mCRPC) and Arms 2 and 3 (LPC). Each arm 
will have a screening period, a treatment period and a post-treatment follow-
up period.  
Re-screening of patients is allowed. Part 1 and Part 2 Arms 1A and 1B will 
enroll patients with mCRPC. Part 2 Arms 2 and 3 will enroll patients with 
newly diagnosed LPC. Enrollment in Part 2 between Arms 1A and 1B and 
between Arms 2 and 3 will be randomized 1:1 to avoid enrollment bias.  
The safety of BNT112 in doses of
and 
µg will be evaluated on the 
DLTs during the first treatment cycle (21 days) and the overall incidence of 
BNT112-related or potentially related AEs in all arms of the trial. The safety 
of concomitant administration of cemiplimab and/or ADT (e.g., goserelin 
acetate) will be evaluated based on the overall incidence of ADT (e.g., 
goserelin acetate) or cemiplimab-related or potentially related AEs in Part 2 
Arms 2 and 3 of the trial, respectively, and will follow the same rules as 
Part 1, until the SRC reviews and confirms that the combination safety profile 
is acceptable. Based on the recommendation from the SRC, the sponsor will 
decide if enrollment should continue for the combination arms. More details 
are provided in the SRC charter. The dose titration part of the trial will 
employ a modified 3 + 3 + 3 design (adopted from Hamberg et al. 201013) 
with cohorts of up to 9 evaluable patients.  
The safety will be evaluated by the SRC. The committee will consist of the 
investigators (especially those who have patients being treated at the dose 
under discussion), the BioNTech trial team including at a minimum, the 
medical monitor, and any other person the investigators/trial team consider 
necessary to assist with trial decisions such as a statistician. The SRC will 
make a recommendation to the sponsor after each meeting on how to proceed 
with the trial and whether to activate the respective expansion arms of the 
trial. The SRC will meet at least every 3 months throughout the trial.  
The efficacy in Part 1 and Part 2 Arm 1A and 1B will be assessed by on-
treatment imaging every 8 weeks (±7 days) for 24 weeks, and then every 
3 months (±7 days) thereafter until disease progression, the start of new anti-
cancer therapy, withdrawal of consent, or death, whichever occurs first. The 
Prostate Cancer Working Group 3 (PCWG3) criteria, and immune-modified 
RECIST (iRECIST) criteria will be used for exploratory endpoint response 
evaluation. If the investigator considers radiographic changes secondary to 
drug-induced inflammation and not to tumor progression, the investigator may 
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postpone a diagnosis of progressive disease until the next radiographic 
evaluation in the trial.  
Following progression after BNT112 monotherapy, patients in Arm 1B have 
the option to be treated with cemiplimab monotherapy.  
The efficacy in Part 2 Arms 2 and 3 will be assessed by tumor measurement 
using mpMRI or MRI at baseline and prior to surgery (i.e., at the end of 
C8/EoT visit). The same imaging modality should be used at screening and at 
all subsequent assessments. 
Various blood- and tumor-based biomarkers will be analyzed in all arms. 
Trial duration: 
First patient was included on 19 December 2019. 
The end of the trial is defined as the date of last patient contact, whether in-
person or by phone, for the last patient in the trial globally, including the 
efficacy follow-up for 12 months after the last dose of trial treatment. 
Safety Review 
Committee (SRC): 
The SRC will review all DLTs and suspected unexpected serious adverse 
reactions, make the REDR recommendation at the end of the Dose Titration 
Part (Part 1) and periodically review safety and efficacy in Part 2.  
The SRC will recommend when expansion arms may be initiated. 
 
 
Plan for statistical 
analysis: 
Statistical Hypotheses 
For each Part 2 Arm 1A and 1B the null hypothesis that the true response rate 
is 5% will be tested against a one-sided alternative (i.e., H0: ORR=5% vs H1: 
ORR>5%). There will be no formal comparison between treatment arms. No 
further statistical hypothesis is under test. 
Sample Size Determination 
The sample size for Part 1 is driven by the 3+3+3 trial design and will range 
from 3 to 9 DLT evaluable patients depending on the number of DLTs which 
may occur. The main objective for the Part 2 is to perform exploratory 
biomarker analyses in the LPC setting and to preliminary assess the efficacy in 
terms of response in the mCRPC setting.  
Simon's two-stage design (Simon, 198931) based on the Minimax approach will 
be used for Part 2 Arm 1A and 1B separately. The null hypothesis that the true 
response rate is 5% will be tested against a one-sided alternative. In the first 
stage, 20 evaluable patients will be treated. Enrollment will continue following 
sponsor decision (upon recommendation from the SRC following review) and 
13 additional evaluable patients may be treated for a total of 33 evaluable 
patients. If there is one or fewer responses in the first 20 evaluable patients, the 
enrollment for that arm may be stopped. The null hypothesis will be rejected if 
five or more responses are observed in 33 evaluable patients. This design yields 
a type I error rate of 2.5% and power of 80% when the true response rate is 
20%. 
A patient will be considered as evaluable if included in the primary analysis set 
(mITT set) which is defined as all patients who are randomized to the IMP and 


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have a baseline and at least one post-baseline (i.e., one on-treatment or post-
treatment) tumor assessment (clinical or imaging assessment). 
No formal sample size calculation is performed for the LPC setting in Part 2 
(Arms 2 and 3) due to its exploratory nature. However, 20 patients are planned 
to be enrolled into Arm 2 and Arm 3. Based on this sample size (N=20) the 
one-sided 95% CI of binary endpoints will have a width of up to +/-0.19 in 
each group depending on the observed effect size. 
Primary Analysis 
DLTs and AEs 
The primary endpoint is the occurrence of DLTs and AEs reported by 
relationship, grade, and seriousness according to NCI CTCAE v5.0. The 
number and percentage of patients with any DLT and/or AE will be presented 
for patients enrolled into Part 1 and for each arm in Part 2. Moreover, a patient 
listing will be provided with all relevant dose exposure data of all patients 
enrolled into Part 1 and for each arm in Part 2 and a listing of all recorded 
DLTs and/or AEs will be presented including the reported term and Medical 
Dictionary for Regulatory Activities (MedDRA®) Preferred Term (PT) and 
System Organ Class (SOC) term, its time of onset, relationship, NCI CTCAE 
grade, and seriousness including dose exposure data (e.g., BNT112 DL). 
Objective Response Rate 
For Arm 1A and 1B in Part 2, ORR is defined as primary efficacy endpoint. 
The ORR is defined as the number of patients with CR or PR as best objective 
response divided by the number of patients in the analysis set. Patients not 
meeting the criteria for CR or PR, including those without any post-baseline 
tumor assessments, will be considered as non-responders. The ORR will be 
summarized with absolute and relative frequencies along with two-sided 95% 
Clopper-Pearson confidence intervals by treatment group/cohort.  
The primary analysis will be performed using the mITT set. 
For Part 1, ORR is defined as secondary endpoint and will be analyzed 
descriptively. 
 
 
 


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1.2. 
Schema 
Figure 1-1: 
Trial Design 
 
 
Abbreviations and Footnotes: 
C = Cycle; IV = intravenous; LPC = localized prostate cancer; mCRPC = metastatic castration-resistant prostate 
cancer; Q3W = every 3 weeks; REDR = recommended expansion dose range. 
* In combination with ADT (e.g., goserelin). 
% Following progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with 
cemiplimab monotherapy
mg IV Q3W. 
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Figure 1-2: 
Treatment Administration – Part 1 and Part 2 
 
 
Abbreviations and Footnotes: 
LPC = localized prostate cancer; mCRPC = metastatic castration-resistant prostate cancer; Q3W = every three 
weeks. 
& 
Recommended dose range (REDR) is confirmed in Part 1. 
* 
Maximum administered dose 
µg; minimum administered dose 
 µg; no dose re-escalation allowed. 
# 
In combination with ADT (e.g., goserelin). 
$ 
From Day 1 of C1 onward, each patient will receive the individual standard dose (or the highest tolerated dose 
from Cycle 1) at each BNT112 administration. 
% 
Following progression after BNT112 monotherapy, patients in Arm 1b have the option to be treated with 
cemiplimab monotherapy 
mg IV Q3W. 
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1.3. 
Schedule of Activities: Part 1 and Part 2 Arms 1A and 1B 
 
Screening 
Treatment 
Follow-up (FU) 
UV 
1 cycle = 21 days 
 
C1[4] 
C2 
C3# 
C4 
C5 
C6 
C7 
C8 
≥C9# 
EoT * 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28d 
≤7d D1 
D8 D15 D1 D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D1 
D30 / 
D90 
M6 M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
±3d 
 
+7d 
±14d ±14d 
 
Patient information/consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history[2] and body 
height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
Physical examination[3] 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X& 
X 
X 
 
 
X[5] 
ECOG PS 
X 
 
X& 
X& 
X& 
X& X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
X 
Vital signs[4] 
X 
X 
X&$ X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ 
X 
X 
 
 
X 
Single 12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
X& 
 
 
 
X[5] 
X[5] 
 
 
X[5] 
Concomitant treatment[6, 7] 
X 
X 
X& 
X& 
X& 
X& X& X& 
X& 
X 
X& 
X& 
X& 
X& 
X& 
X 
X& 
X 
X 
X 
X 
X[5] 
Tumor response assessment[8] 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X[5] 
 
 
 
X 
Archival FFPE tumor tissue 
sample 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsy sample 
(optional)[10] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional tumor sample[21] 
 
 
(X) 
 
 
 
 
Inclusion/Exclusion criteria 
X 
X 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization[22] 
 
 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP Administration 
Part 1 (monotherapy dose titration)  
BNT112 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Part 2 Arm 1A (with cemiplimab) 
BNT112 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Cemiplimab (IMP) 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Part 2 Arm 1B (monotherapy) 
IMP 1 admin. Arm: BNT112 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 


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Screening 
Treatment 
Follow-up (FU) 
UV 
1 cycle = 21 days 
 
C1[4] 
C2 
C3# 
C4 
C5 
C6 
C7 
C8 
≥C9# 
EoT * 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28d 
≤7d D1 
D8 D15 D1 D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D1 
D30 / 
D90 
M6 M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
±3d 
 
+7d 
±14d ±14d 
 
Safety laboratory tests [11] 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
X 
 
X& 
X& 
X& X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
X [5]  
Coagulation 
 
X 
 
 
 
X& 
 
 
 
 
X& 
 
X& 
 
X& 
 
X& 
X 
X 
 
 
X [5] 
Blood chemistry 
 
X 
 
X& 
X& 
X& X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
(X) [5] 
Thyroid hormones [18, 20] 
 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X20 
 
X 
 
 
(X)[5] 
Urinalysis 
 
X 
 
X& 
X& 
X& X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
(X) [5] 
 
AE/TEAE [12, 13] 
X 
X 
X&$ X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ 
X 
X 
 
 
X 
Survival/disease status [14] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Blood Biomarkers 
Cytokines 
 
 
X[15] X[15] X[15] X[15] X[15] X[15] X[15] 
 
X[17] X[17] X[17] X[17] X[17] 
 
X[17] 
X 
X 
 
 
(X) 
PSA 
 
X 
X[16] X[16] X[16] X[16] X 
[16] X[16] X[16] 
 
X[16] X[16] X[16] X[16] X[16] 
 
X[16] 
X 
X 
 
 
(X) 
Testosterone 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
ELISpot and further immune 
monitoring 
 
X[18] 
 
 
  
 
 
 
X 
 
 
 
 
 
X 
 
X[19] 
X[19] 
 
 
(X) 
HLA typing 
 
X[18] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCR profiling 
 
X[18] 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X[19] 
X[19] 
 
 
(X) 
Circulating tumor cells [9] 
(X) 
(X) 
 
 
 
 
Abbreviations and Footnotes: 
X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done before and after IMP administration; (X) = optional; AE = adverse event; 
C = cycle (One cycle is defined as 21 days); D = day of cycle; d = day(s); DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology 
Group performance status; h = hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; FFPE = formalin-fixed, paraffin-embedded; FU = follow-up; 
HLA = human leukocyte antigen; IMP = investigational medicinal product; PSA = prostate-specific antigen; SRC = Safety Review Committee; TCR = T cell receptor; 
TEAE = treatment-emergent AE; UV = unscheduled visit. 
# 
Starting with C3D1, treatment will be administered every 3 weeks until a discontinuation-of-treatment criterion is met. Planned visit schedule until C8 is shown in table. 
From Cycle 8 on, coagulation, blood chemistry, hematology, and urinalysis will be measured every second cycle (i.e., C8, C10, C12, etc.) unless clinically indicated. 


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Protocol number: RN5609C00 version 6.0 
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* 
EoT assessments will be performed up to 21 days after administration of the last dose of IMP for patients who discontinued trial treatment, except if patient was lost to 
follow-up or died or the EoT visit may be combined with the Safety FU-D30 visit. For patients of Arm 1B who will optionally start cemiplimab monotherapy as outlined in 
the Schedule of Activities shown in Section 1.5, the EoT visit may be combined with visit CemC1 if both visits are to happen with less than 7 days difference. 
** 
All patients (Part 1 and 2) will be actively followed up for safety (FU-D30) after last intake of BNT112. Patients in Part 2 Arm 1A will be followed up for safety (FU-D90) 
after last intake of cemiplimab or (FU-D30) after last intake of BNT112, whichever is later. All patients will be followed up for efficacy (FU-M6 after the last intake of IMP, 
FU-M12 after the last intake of IMP). Within 28 days after confirmation of disease progression, patients of Arm 1B can optionally start cemiplimab monotherapy and will 
follow the Schedule of Activities shown in Section 1.5 after performing the EoT for BNT112 treatment.  
[1] 
The patient ICF for trial participation must be signed before any trial-related research procedures or interventions are performed, see Section 10.1.3. Patients who agree to 
additional optional tumor biopsy sample(s) in case these are taken at the time of disease progression must give written consent for this. Refusal to give consent for the 
optional tumor biopsy sample(s) does not exclude a patient from participation in the trial. 
[2] 
Documentation of prostate cancer history and treatments, previous/ongoing concomitant diseases and tetanus vaccination status (see Section 8.3.2).  
[3] 
A comprehensive physical examination will be performed at screening and abbreviated physical examinations (overall health judgment and change of symptoms) from C1D1 
onwards prior to IMP administration, see Section 8.2.1. 
[4] 
Vital signs (blood pressure, pulse rate, body temperature) should be assessed pre-treatment and 1 h (±15 min), 4 h (±1 h) and 6 h (±1 h) post-treatment and as clinically 
indicated during C1. Patients must be observed for at least 4 to 6 h after administration of BNT112 and vital signs collected pre-treatment, 4 to 6 h (±1 h) post-treatment and 
as clinically indicated. 
[5] 
Only if clinically indicated. 
[6] 
All prior prostate cancer-related drug treatment will be recorded; other prior medication only for the period of 28 days before the planned IMP administration. 
[7] 
The period for documentation of concomitant treatment extends from C1D1 until Safety FU-D30 visit. Details of systemic anti-cancer treatments or non-drug anti-cancer 
therapies (e.g., radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of the FU period (i.e., up to Efficacy FU-
M12). 
[8] 
Bone scans and CT/MRI of the chest, abdomen, and pelvis will be done at screening, every 8 weeks for the first 24 weeks and every 3 months thereafter (window for tumor 
assessment is ±7 days of respective visit day). PCWG3 and iRECIST guidelines for imaging will apply. See Section 8.1.1.1. 
[9] 
Only if routinely performed locally.  
[10] 
Patients in Part 1 and Part 2 Arm 1A and Arm 1B will be asked if they are willing to provide optional tumor biopsy sample(s) in case these are taken at the time of disease 
progression.  
[11] 
For details on safety laboratory tests, see Section 10.2. If the time interval between screening laboratory tests and C1D1 (baseline) is more than 7 days, tests must be repeated 
at C1D1. Screening serum creatinine will be used to calculate patient’s glomerular filtration rate required for inclusion criterion. If warranted by dipstick results, urine 
sediment will be microscopically examined. Serology can be done at earlier screening time point. 
[12] 
At treatment visits, patients will also be monitored for TEAEs for at least 4 to 6 h post-treatment. 
[13] 
For details on DLT assessment period and DLT criteria, see Sections 6.6.1.2 and 6.6.1.1. 
[14] 
For details on patient’s survival status and disease status, see Sections 10.9 and 8.1. 
[15] 
Blood collection before and 4 h (±30 min) after administration of BNT112. 
[16] 
Blood collection before administration of BNT112. 
[17] 
Blood collection 4 h (±30 min) after administration of BNT112. 
[18] 
Variable time point; either during screening ≤7 d or at C1D1 before administration of BNT112. 
[19] 
A sample should be taken at EoT or at Safety FU and only if one has not previously been taken at C8D15. 
[20] 
At screening for all patients, thereafter only for Arm 1A: thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) will be 
performed at the times listed and every second cycle after C8 and when clinically indicated at the investigator’s discretion. 
[21] 
On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for 
additional potential biomarker research. 
[22] 
Randomization can be performed up to 1 day before C1D1. 
 


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1.4. 
Schedule of Activities: Part 2 Arms 2 and 3 
 
Screening  
Treatment 
Follow-up (FU) 
UV 
Surgery 
1 cycle = 21 days 
 
 
C1 
C2 
C3 
C4 
C5 
C6 
C7 
C8 
EoT* 
Safety FU ** 
Efficacy 
FU ** 
Visit 
≤28d ≤7d 
D1 
D8 
D15 D1 
D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D30/ 
D90 
M6  
M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
 
+7d 
±14d ±14d 
Patient information/ 
consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history[2] and 
body height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
 
 
 
X 
X 
 
 
 
 
Physical examination[3] 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
 
X[5] 
 
ECOG PS 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X 
 
Vital signs[4] 
X 
X 
X&$ 
X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X 
X 
 
 
X 
 
Single 12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
X& 
 
 
X[5] 
X[5] 
 
 
X[5] 
 
Concomitant    
treatment[6, 7] 
X 
 
X 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
X 
X& 
X& 
X& 
X& 
X& 
X 
X 
X 
X 
X 
X[5] 
 
Tumor response 
assessment[8, 13] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
(X) 
 
 
 
X 
(X) 
Tumor tissue 
(mandatory)[9] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional tumor 
sample[22] 
 
 
(X) 
 
 
 
 
 
Inclusion/Exclusion 
criteria 
X 
X 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization[23] 
 
 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP/NIMP administration: 
Part 2 Arm 2 (with cemiplimab)  
BNT112 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Cemiplimab (IMP) 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
ADT (NIMP) [11] 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 


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Protocol number: RN5609C00 version 6.0 
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Screening  
Treatment 
Follow-up (FU) 
UV 
Surgery 
1 cycle = 21 days 
 
 
C1 
C2 
C3 
C4 
C5 
C6 
C7 
C8 
EoT* 
Safety FU ** 
Efficacy 
FU ** 
Visit 
≤28d ≤7d 
D1 
D8 
D15 D1 
D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D30/ 
D90 
M6  
M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
 
+7d 
±14d ±14d 
Part 2 Arm 3 (monotherapy) 
BNT112 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
ADT (NIMP) [11] 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests [12] 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X[5] 
 
Coagulation 
 
X 
 
 
 
X& 
 
 
 
 
X& 
 
X& 
 
X& 
 
X 
X 
 
 
X[5] 
 
Blood chemistry 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X[5] 
 
Thyroid hormones [19, 21] 
 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
(X)[5] 
 
Urinalysis 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X 
 
 
AE/TEAE[14] 
X 
X 
 
X&$ 
X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X 
X 
 
 
X 
 
Survival/disease 
status[15] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Blood Biomarkers 
Cytokines  
 
 
X[16] 
X[16] X[16] X[16] X[16] 
 
X[16] 
 
X[18] X[18] X[18] X[18] X[18] 
 
X 
X 
 
 
(X) 
 
PSA  
 
X 
X[17] 
X[17] X[17] X[17] X[17] X[17] X[17] 
 
X[17] X[17] X[17] X[17] X[17] 
 
X 
X 
X 
X 
(X) 
X [20] 
ELISpot and further 
immune monitoring 
 
X[19] 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X[10] 
X[10] 
 
 
(X) 
 
HLA typing  
 
X[19] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCR profiling  
 
X[19] 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X[10] 
X[10] 
 
 
(X) 
 
Abbreviations and Footnotes 
X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done before and after IMP administration; (X) = optional; ADT = androgen-
deprivation therapy (e.g., goserelin acetate); AE = adverse event; C = cycle (One cycle is defined as 21 days); CT = computed tomography; D = day of cycle; d = day(s); ECG = 
electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; h = hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; 
FFPE = formalin-fixed, paraffin-embedded; FU = follow-up; HLA = human leukocyte antigen; IMP = investigational medicinal product; mpMRI = multi-parametric magnetic 
resonance imaging; MRI = magnetic resonance imaging; NIMP = non-investigational medicinal product; PSA = prostate-specific antigen; REDR = recommended expansion dose 
range; TCR = T cell receptor; TEAE = treatment-emergent adverse event; UV = unscheduled visit; h = hour(s). 
* 
EoT assessments will be performed up to 21 days after administration of the last dose of IMP for patients who discontinued trial treatment, except if patient was lost to 
follow-up or died or the EoT visit may be combined with the Safety FU-D30 visit.  


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** 
All patients (Part 1 and 2) will be actively followed up for safety (FU-D30) after last intake of BNT112. Patients in Part 2 Arm 2 will be followed up for safety (FU-D90) 
after last intake of cemiplimab or (FU-D30) after last intake of BNT112, whichever is later. Efficacy FU-M6 and M12 are performed for Part 2 Arms 2 and 3 after last IMP 
administration 
[1] 
The patient ICF for trial participation must be signed before any trial-related research procedures or interventions are performed, see Section 10.1.3. Patients who agree to 
additional optional sampling must give written consent for this. Refusal to give consent for the optional sample(s) does not exclude a patient from participation in the trial, see 
Section 10.1.3. 
[2] 
Documentation of prostate cancer history and treatments, previous/ongoing concomitant diseases and tetanus vaccination status (see Section 8.3.2).  
[3] 
A comprehensive physical examination will be performed at screening and abbreviated physical examinations overall health judgment and change of symptoms) from C1D1 
onwards prior to IMP administration, see Section 8.2.1. 
[4] 
 For all patients, vital signs (blood pressure, pulse rate, body temperature) should be assessed pre-treatment and 1 h (±15 min), 4 h (±1 h) and 6 h (±1 h) post-treatment and as 
clinically indicated during C1. Patients must be observed for at least 4 to 6 h after administration of BNT112 and vital signs collected pre-treatment, 4 to 6 h (±1 h) post-
treatment and as clinically indicated. 
[5] 
Only if clinically indicated. 
[6] 
All prior prostate cancer-related drug treatment will be recorded; other prior medication only for the period of 28 days before the planned IMP administration.  
[7] 
The period for documentation of concomitant treatment extends from C1D1 until Safety FU-D30 visit (Part 2 Arm 3) or FU-D90 (Part 2 Arm 2). Details of systemic anti-
cancer treatments or non-drug anti-cancer therapies (e.g., radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of 
the FU period (i.e., up to Efficacy FU-M12).  
[8] 
Tumor measurement using mpMRI or MRI (window for tumor assessment is ±7 days of respective visit day). The same imaging modality should be used at screening and at 
all subsequent assessments. For details on tumor imaging and time points, see Section 8.1.1.  
[9] 
An FFPE tumor sample from the diagnostic biopsy must be provided during screening. A fresh tissue sample must be provided from surgery; only if this is not feasible an 
FFPE tumor sample will be obtained.  
[10] 
A sample should be taken at EoT or at Safety FU and only if one has not previously been taken at C8D15. 
[11] 
The ADT administration should take place between 7 days before Day 1 and 12 weeks after the first administration. 
[12] 
For details on safety laboratory tests, see Section 10.2. If time interval between screening laboratory tests and C1D1 (baseline) is more than 7 days, tests must be repeated at 
C1D1. Screening serum creatinine will be used to calculate patient’s glomerular filtration rate required for inclusion. If warranted by dipstick results, urine sediment will be 
microscopically examined. Serology can be done at earlier screening time point. 
[13] 
For details on response assessment, please refer to Section 8.1.1.2. 
[14] 
At treatment visits, patients will also be monitored for TEAEs 4 to 6 h post-treatment. 
[15] 
For details on patient’s survival status and disease status, see Section 10.9 and Section 8.1. 
[16] 
Blood collection before and 4 h after administration of BNT112. 
[17] 
Blood collection before administration of BNT112. 
[18] 
Blood collection 4 h (±30 min) after administration of BNT112. 
[19] 
Variable time point; either during screening ≤7 d or at C1D1 before administration of BNT112. 
[20] 
At 6 weeks (± 1 week) after the surgery (radical prostatectomy). 
[21] 
Only for Arm 2 (and at screening for all patients if the patient is not yet randomized), thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and 
triiodothyronine [T3]) will be performed at the times listed and as clinically indicated at the investigator’s discretion. 
[22]  On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for 
additional potential biomarker research. 
[23] 
Randomization can be performed up to 1 day before C1D1. 


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1.5. 
Schedule of Activities: Part 2 Arm 1B – Optional Cemiplimab Treatment Following Progression 
after BNT112 Monotherapy 
 
Treatment# 
Follow-up (FU) 
UV 
1 cycle = 21 days 
CemC1 
≥CemC2 
EoT * 
Safety FU ** 
Efficacy FU ** 
Visit 
 
 
 
D90 
M6 
M12 
Visit window 
≤28 d after progression 
in Arm 1b 
±3d 
  
+7d 
±14d 
±14d 
 
Patient information/consent for 
cemiplimab monotherapy[1] 
X@ 
 
 
 
 
 
 
Physical examination[2] 
X& 
X& 
X 
X 
 
 
X[3] 
ECOG PS 
X& 
X& 
X 
X 
 
 
X 
Vital signs 
X&$ 
X&$ 
X 
X 
 
 
X 
Single 12-lead ECG 
X& 
X&[14] 
X[3] 
X[3] 
 
 
X[3] 
Concomitant treatment[5] 
X& 
X& 
X 
X 
X 
X 
X[3] 
Tumor response assessment[6] 
X 
X[3] 
 
 
 
 
Optional tumor sample[7] 
(X) 
 
 
 
 
IMP Administration 
Cemiplimab (IMP) 
X 
X 
 
 
 
 
 
Safety laboratory tests [8] 
Hematology 
X& 
X& 
X 
X 
 
 
X[3] 
Coagulation[4] 
X& 
X 
X 
 
 
X[3] 
Blood chemistry 
X& 
X& 
X 
X 
 
 
(X)[3] 
Thyroid hormones[4] [9]  
X 
 
X 
 
 
(X)[3] 
Urinalysis 
X& 
X& 
X 
X 
 
 
(X)[3] 
 
AE/TEAE [10] 
X&$ 
X&$ 
X 
X 
 
 
X 
Survival/disease status [11] 
 
 
 
 
X 
X 
 


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Treatment# 
Follow-up (FU) 
UV 
1 cycle = 21 days 
CemC1 
≥CemC2 
EoT * 
Safety FU ** 
Efficacy FU ** 
Visit 
 
 
 
D90 
M6 
M12 
Visit window 
≤28 d after progression 
in Arm 1b 
±3d 
  
+7d 
±14d 
±14d 
 
Blood Biomarkers 
PSA 
X& 
X& 
X 
X 
 
 
(X) 
Testosterone 
 
 
 
 
 
 
(X) 
ELISpot and further immune 
monitoring 
 
X[12] 
 
 
 
 
TCR profiling 
 
X[12] 
 
 
 
 
Circulating tumor cells [13] 
(X) 
 
 
 
 
 
Abbreviations and Footnotes: 
X@ to be done before any CemC1-specific procedure or intervention; X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done 
before and after IMP administration; (X) = optional; AE = adverse event; CemC = cycle (One cycle is defined as 21 days); d = day(s); ECG = electrocardiogram; 
ECOG PS = Eastern Cooperative Oncology Group performance status; h = hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; FFPE = formalin-
fixed, paraffin-embedded; FU = follow-up; IMP = investigational medicinal product; mCRPC = metastatic castration-resistant prostate cancer; PSA = prostate-specific antigen; 
SRC = Safety Review Committee; TCR = T cell receptor; TEAE = treatment-emergent adverse event; UV = unscheduled visit. 
# 
Treatment will be administered every 3 weeks until a discontinuation-of-treatment criterion is met. 
* 
EoT assessments will be performed up to 21 days after administration of the last dose of cemiplimab for patients who discontinued trial treatment, except if patient was lost to 
follow-up or died.  
** 
All patients will be actively followed up for safety (FU-D90) after last intake of cemiplimab. All patients will be followed up for efficacy (FU-M6 after the last intake of IMP, 
FU-M12 after the last intake of IMP). 
[1] 
The patient ICF for cemiplimab monotherapy must be signed before any trial-related research procedures or interventions are performed on CemC1, see Section 10.1.3. 
Patients who agree to additional optional sampling must give written consent for this. Refusal to give consent for the optional sample(s) does not exclude a patient from 
participation in this part of the trial, see Section 10.1.3. 
[2] 
A comprehensive physical examination will be performed at CemC1 and abbreviated physical examinations (overall health judgment and change of symptoms) from CemC2 
onwards prior to IMP administration, see Section 8.2.1. 
[3] 
Only if clinically indicated. 
[4] 
Assessments will be performed at CemC1 and then every second cycle (every 6 weeks) 
[5] 
The period for documentation of concomitant treatment extends from CemC1 until Safety FU-D90 visit. Details of systemic anti-cancer treatments or non-drug anti-cancer 
therapies (e.g., radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of the FU period (i.e., up to Efficacy FU-
M12).  
[6] 
Bone scans and CT/MRI of the chest, abdomen, and pelvis will be done every 3 months (window for tumor assessment is ±7 days of respective visit day). PCWG3 and 
iRECIST guidelines for imaging will apply. See Section 8.1.1.1. 
[7] 
On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for 
additional potential biomarker research. 


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Protocol number: RN5609C00 version 6.0 
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[8] 
For details on safety laboratory tests, see Section 10.2. If warranted by dipstick results, urine sediment will be microscopically examined. 
[9] 
Thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) will be performed every 6 weeks, at Safety FU D90, or as clinically 
indicated at the investigator’s discretion. 
[10] 
At treatment visits, patients will also be monitored for TEAEs at site, according to local prescribing guidelines for cemiplimab. 
[11] 
For details on patient’s survival status and disease status, see Sections 8.1 and 10.9. 
[12] 
Sampling at CemC3 or at EoT, whichever occurs first. 
[13] 
Only if routinely performed locally. 
[14] 
Assessments will be performed at CemC1, CemC4, CemC7 and when considered as clinically indicated by the investigator. 
 


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2. 
Introduction 
2.1. 
Background 
2.1.1. 
Overview of the Disease(s) 
Prostate cancer is the second most common malignant neoplasm in men worldwide, with an 
estimated 1,276,106 incidences and 358,989 deaths in 2018. The incidence of prostate cancer has 
increased over the past 20 years (largely due to the wide availability of prostate-specific antigen 
[PSA] testing), and currently prostate cancer is the most frequently diagnosed cancer among men 
worldwide (13.5%); in Germany (18.9%), the United Kingdom (UK; 23.6%) and in the United 
States of America (USA; 18.5%). Although mortality rates do not follow those of incidence, 
prostate cancer is still the fifth cause of cancer-related death worldwide (6.7%) and the leading 
cause of cancer deaths among men in 46 less-developed countries.5, 6 
PSA is a protein exclusively generated in prostate cells and high levels of PSA in the blood are 
often an indication of prostate cancer. Blood levels of PSA are commonly used to gauge the 
success of treatment, and the presence of recurrence. The risk of clinically significant prostate 
cancer is related to age, ethnicity, family history, PSA level, free/total PSA ratio, and findings 
from digital rectal examination.32 PSA screening for prostate cancer reduces prostate cancer 
mortality by allowing early diagnosis of the disease and implementation of curative treatments in 
many patients.  
In Western countries, most patients with prostate cancer are diagnosed with local disease and 
present with a low, intermediate, or high-risk of biochemical relapse. Approximately 15% of 
patients are classified as high-risk LPC.24 These patients are at an increased risk of recurrence, 
need for secondary therapy, metastatic progression, and death from prostate cancer. These 
patients have a significant overall survival (OS) benefit from radical prostatectomy, with a 
relative risk reduction in mortality of 31%.7 LPC remains a major cause of mortality, as the 
prostate cancer mortality worldwide during the 15 years after local treatment ranges from 6 to 
121 deaths per 1000 persons per year, depending on the Gleason score.32 Selection of an efficient 
treatment strategy is crucial for patients with high-risk LPC. Recently, multimodal treatment 
approaches that combine systemic and local therapies have been introduced and offer a 
promising strategy for improving the clinical outcomes of patients with LPC.10 This includes 
chemotherapy, hormonal therapy, as well as newly introduced immune checkpoint inhibitors and 
anti-cancer vaccines. 
In patients with recurrent or metastatic prostate cancer, there is initial benefit from hormonal 
therapies; however, patients invariably stop responding to ADT, a state known as castration-
resistant prostate cancer (CRPC). Although multiple new agents have been approved for 
metastatic CRPC (mCRPC) over the last decade which prolong survival and provide palliative 
benefit36, as of today there is no curative treatment for mCRPC available. The prognosis for 
patients with mCRPC is variable with median OS ranging from 16 to 34 months.  
Despite advances in treatment of both LPC and mCRPC, the unmet medical need for these 
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According to the guidelines of the European Association of Urology - European Society for 
Radiotherapy & Oncology - International Society of Geriatric Oncology, the initial treatment 
with curative intent for LPC includes surgery (i.e., radical prostatectomy), or dose-escalated 
intensity-modulated radiation therapy in combination with ADT.1 However, the latter treatment 
is associated with increased risk of death from cardiovascular diseases.25 Radical prostatectomy 
as a single modality leaves about 30% of patients with positive surgical margins after radical 
prostatectomy and about 30% of these patients experience biochemical recurrence.  
The benefit of combined ADT and radiotherapy in patients with locally advanced prostate cancer 
has been proved in randomized clinical trials.22, 23, 33 This treatment modality is now also 
recommended in patients with high-risk LPC.4 For example, goserelin acetate (Zoladex®) is 
approved as neoadjuvant treatment prior to radiotherapy and is also used prior to radical 
prostatectomy in patients with high-risk localized or locally advanced prostate cancer where 
Zoladex® has demonstrated improved disease-free survival (DFS). Neoadjuvant systemic 
treatments have been investigated for many years, so far without evidence from Phase 3 
randomized trials regarding the benefit of neoadjuvant treatment in LPC patients. There are 
two outcomes for neoadjuvant treatment: (i) reduction of tumor volume facilitating complete 
surgical resection, providing the control of microscopic metastatic disease and to assess the 
treatment effect in the tissue performing accurate staging of the disease, Gleason score and 
surgical margins and (ii) a prolonged effect of neoadjuvant treatment on OS or its surrogate. A 
meta-analysis published in 2017 of randomized controlled trials in patients with LPC showed 
that metastasis-free survival is a strong surrogate of OS.27  
In order to establish better neoadjuvant treatment options for patients with high-risk LPC, several 
Phase 1 and Phase 2 studies are ongoing that implement novel immunotherapies in combination 
with hormone deprivation therapies or chemotherapies. 
The initial treatment of choice for metastatic prostate cancer is medical or surgical castration 
with hormonal therapy being the standard of care since the 1940s. However, prostate cancer 
inevitably progresses to CRPC after 16 to 34 months on ADT. Currently, mCRPC is usually 
treated with chemotherapy (docetaxel, mitoxantrone, and cabazitaxel) or secondary hormonal 
therapeutic agents such as abiraterone or enzalutamide.26 Immunotherapy with sipuleucel-T has 
been employed in treating asymptomatic or minimally metastatic CRPC without visceral 
metastasis. Bone metastasis is managed with zoledronic acid, denosumab, or radium-223.38 
Radium-223 is used for symptomatic bone metastasis without visceral metastasis.11 However, the 
effects of these treatments are less than satisfactory, and the need for novel agents in treating 
mCRPC is still present. 
2.1.2. 
Introduction to the Investigational Medicinal Products 
2.1.2.1. 
BNT112 (IMP 1) 
BNT112 (previously referred to as W_pro1 in this and other trial-related documentation) consists 
of messenger RNA (mRNA; further referred to as RNA) targeting 5 antigens expressed in 
de novo and metastatic prostate cancer that are separately complexed with liposomes to form 
serum-stable RNA lipoplexes (RNA-LPXs). The RNA molecules are immune-pharmacologically 
optimized for high stability, translational efficiency and presentation on major histocompatibility 
complex (MHC) class I and II molecules.17, 28, 18 Following preparation, the final products are 
administered as five separate, consecutive IV injections. 


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The MoA of RNA-LPX vaccination relies on the recruitment of antigen-specific T-lymphocytes 
after presentation of peptide-epitopes derived from the RNA-encoded antigens on MHC 
molecules by professional antigen-presenting cells (APCs), and toll-like receptor (TLR)-
mediated immune-modulatory effects, which lead to cell activation and to the induction of 
pro-inflammatory cytokines such as type I interferons (IFNs), thereby enhancing the vaccination 
effects.16  
The IV injected RNA-LPXs are selectively taken up by professional APCs in secondary 
lymphatic tissues including spleen, lymph nodes, and bone marrow. The RNA-encoded antigens 
are presented by APCs and induction of vaccine antigen-specific CD8+ and CD4+ T cell 
responses and T cell memory is initiated.17 This is further supported by the local RNA-LPX –
induced immune-modulation in the lymphoid compartments. In addition, BNT112 also has the 
potential to induce dendritic cell activation. 
2.1.2.2. 
Cemiplimab (LIBTAYO®; IMP 2) 
Cemiplimab is a high affinity IgG4P human antibody to the PD-1 receptor (PDCD1, CD279) that 
blocks PD-1/PD-L1-mediated T cell inhibition. Cemiplimab is approved in the US, European 
Union (EU), Canada and other countries for the treatment of advanced cutaneous squamous cell 
carcinoma (CSCC), patients with non-small cell lung cancer (NSCLC) expressing PD-L1 (in 
≥50% tumor cells), and locally advanced or metastatic basal cell carcinoma (BCC)41, 42, 43. 
Additional background information on the trial drug and development program can be found in 
the latest version of the cemiplimab Investigator’s Brochure (IB). 
2.1.3. 
Non-Investigational Medicinal Products (NIMP) 
2.1.3.1. 
Androgen-deprivation therapy followed by radical prostatectomy 
Patients should be eligible for up to 6 months of ADT followed by radical prostatectomy. The 
sponsor will provide goserelin acetate if requested by the investigational site, however other 
types of ADT are allowed according to local clinical practice. In such cases, the investigational 
site will organize and reimburse the ADT of choice. The ADT can be interrupted any time prior 
to the radical prostatectomy and/or other clinically indicated treatment or intervention based on 
the investigator’s decision. 
Goserelin acetate (e.g., Zoladex® LA 10.8 mg implant): The luteinizing hormone-releasing 
hormone (LHRH) agonist Goserelin acetate, (synonym: D-Ser(But)6Azgly10-LHRH) is a 
synthetic analogue of the naturally occurring gonadotropin releasing hormone. Goserelin acetate 
10.8 mg is indicated in the treatment of metastatic or locally advanced prostate cancer and as 
adjuvant treatment to radical prostatectomy or radiotherapy, and as neoadjuvant treatment prior 
to radiotherapy in patients with high-risk localized or locally advanced prostate cancer. Goserelin 
acetate is injected subcutaneously (SC) into the anterior abdominal wall every 12 weeks 
(Q12W). On chronic administration, goserelin acetate results in inhibition of pituitary luteinizing 
hormone secretion leading to a fall in serum testosterone concentrations in males and serum 
estradiol concentrations in females. This effect is reversible on discontinuation of therapy. 
Initially, goserelin acetate, like other LHRH agonists, may transiently increase serum 
testosterone concentration in men and serum estradiol concentration in women. In men, by 
around 21 days after the first depot injection, testosterone concentrations have fallen to within 


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the castrate range and remain suppressed with treatment Q12W. This inhibition leads to prostate 
tumor regression and symptomatic improvement in the majority of patients.  
In the management of patients with metastatic prostate cancer, goserelin acetate has been shown 
in comparative clinical trials to give similar survival outcomes to those obtained with surgical 
castrations. In comparative trials, goserelin acetate has been shown to improve DFS and OS 
when used as an adjuvant therapy to radiotherapy in patients with LPC (T1-T2 and PSA of at 
least 10 ng/mL or a Gleason score of at least 7), or locally advanced (T3-T4) prostate cancer.  
Very common (≥1/10) adverse drug reactions (ADRs) include hot flushes, hyperhidrosis, a 
decrease in libido and erectile dysfunction. These are pharmacological effects which seldom 
require withdrawal of therapy. Hyperhidrosis and hot flushes may continue after stopping 
goserelin acetate. For full details, see the Summary of Product Characteristics (SmPC) for 
Zoladex® LA 10.8 mg implant.3 
Goserelin acetate is currently approved for the treatment of locally advanced prostate cancer. For 
the purposes of this trial, goserelin acetate is being used as a component of primary therapy for 
LPC, as outlined in the respective country prescribing information.  
2.2. 
Trial Rationale 
Over the last few years, immunotherapy has become a promising part of the treatment of various 
solid tumors. Since ipilimumab (Yervoy®, an anti-cytotoxic T-lymphocyte-associated protein 
[CTLA]-4 monoclonal antibody; Bristol-Meyer Squibb, Princeton, New Jersey, USA), was first 
approved in 2010 in the USA for late-stage melanoma, a number of new immunotherapy agents 
have entered development. Most notably, agents that block the programmed cell death receptor-1 
(PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis have been shown to prolong survival in 
patients with NSCLC, melanoma, kidney cancer, head and neck cancer, and others. Adoptive 
cellular therapy, mainly chimeric antigen receptor T cells, has shown activity in melanoma, 
lymphomas and leukemia. In prostate cancer, a vaccine-based active cellular therapy (sipuleucel-
T [Provenge®]; Dendreon Corporation, Seattle, Washington, USA) is approved for mCRPC.  
The new strategy of combining tumor vaccination with checkpoint inhibitors is being developed 
as potentially effective in cancer treatment. Nivolumab plus a multi-peptide vaccine (gp100, 
MART-1 [melanoma antigen recognized by T cells 1], and NY-ESO-1 [New York esophageal 
squamous cell carcinoma-1] with Montanide ISA 51 VG) has been investigated as adjuvant 
therapy in resected stage IIIC and IV melanoma patients in a Phase 1 trial, where the 
combination showed an acceptable safety profile. Despite this early success and the promise 
shown by the immune checkpoint inhibitors in other cancer types, immunotherapy in prostate 
cancer has been less effective than hoped for, with negative results in studies of checkpoint 
inhibitors15 and those with other vaccines such as GVAX® (VITAL-1 and VITAL-2) and 
Prostvac (PROSPECT).  
Immunotherapy for prostate cancer has many challenges to overcome, including lack of tumor 
immunogenicity as well as the major obstacle that prostate cancer is poorly infiltrated by T cells 
as compared to some of the more responsive tumor types where checkpoint inhibitors are already 
approved. The lack of efficacy of checkpoint inhibitors is probably caused by both the low 
expression of checkpoint ligands on prostate tumors and the low mutational burden in prostate 
cancers. Conversely, prostate cancer expresses several antigens restricted to the organ itself and 


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maintained in the process of malignant transformation (e.g., prostate-specific membrane antigen, 
PSA and prostatic acid phosphatase [PAP]), which makes it a good target for vaccines, 
potentially turning the “cold” tumors to “hot.”  
This Phase 1/2A safety, immunogenicity, pharmacodynamics, and efficacy trial with RNA-LPX 
vaccine targeting 5 tumor-associated antigens (TAAs) specific for de novo as well as metastatic 
prostate cancer, discovered and developed by BioNTech RNA Pharmaceuticals GmbH, 
predecessor of BioNTech SE (hereinafter referred to as “sponsor”), will be conducted in both 
neoadjuvant for LPC, and mCRPC settings. The clinical trial will initially start enrolling only 
mCRPC patients who have progressed after two prior lines of systemic therapy. After initial 
safety of the vaccine monotherapy is established, four expansion cohorts will be opened 
including two for newly diagnosed patients with high-risk LPC eligible for up to 6-month 
treatment with ADT (e.g., goserelin acetate) followed by radical prostatectomy. Patients with 
mCRPC will be given the option to be treated with cemiplimab monotherapy following 
progression after BNT112 monotherapy. 
This clinical setting was selected based on the following rationale: 
i. 
it provides a unique opportunity for the patients whose immune systems have not yet 
been exposed to prior hormonal and/or chemo/radiotherapy where an immunotherapy is 
believed to have the potential to stimulate long-lasting anti-tumor immune responses;  
ii. 
the addition of BNT112 monotherapy and combination with cemiplimab does not 
interfere with the established clinical practice and will not delay the planned treatment for 
these patients (i.e., the hormonal therapy followed by planned radical prostatectomy); 
iii. 
the addition of cemiplimab will begin to test the hypothesis that the immune response to 
tumor cells generated by the vaccine can be enhanced by the addition of a checkpoint 
inhibitor39; 
iv. 
the clinical setting provides a unique opportunity to study tumor-related biomarkers 
utilizing biopsies which are part of the established diagnostic work-up of the newly 
diagnosed patients; 
v. 
careful safety monitoring including implementation of the SRC, which ensures the safety 
and well-being of the patients enrolled in this trial; 
vi. 
it provides an opportunity for patients treated with BNT112 monotherapy to be treated 
with the anti-PD-1 cemiplimab after progression and to check the potential benefit of a 
sequential therapy. 
The RNA-LPX cancer vaccine induces activation of both the adaptive immune system (vaccine 
antigen-specific CD8+/CD4+ T cell) as well as the innate immune system (TLR7-agonism of 
single-stranded RNA). The physiology of efficient induction, expansion and differentiation of 
antigen-specific T cells is associated with PD-1 upregulation on these T cells. Thus, the cancer 
vaccine is expected to have a synergistic MoA with anti-PD-1. One reason for treatment failure 
in patients treated with PD-1/PD-L1 blockade is the lack of preformed antigen-specific T-
lymphocytes recognizing relevant tumor antigens. These are generated by the RNA-LPX cancer 
vaccine, which induces potent antigen-specific CD4+ and CD8+ T cell responses. These T cells 
not only execute direct anti-tumor activity by their cytotoxicity upon recognition of their target 
antigens on tumor cells, but they also induce inflammation (e.g., IFNγ secretion) in the tumor 
microenvironment thereby sensitizing tumor cells to the therapeutic effects of checkpoint 
inhibitors. The contribution of both mechanisms to anti-tumor efficacy is supported by non-


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clinical studies in mice bearing syngeneic tumors treated with RNA-LPX vaccine alone or in 
combination with anti-PD-1/PD-L1 blockade.  
In summary, the MoA of BNT112 both in monotherapy and in combination with the anti-PD-1 
immune checkpoint inhibitor cemiplimab, together with carefully selected and refined clinical 
setting, presents a unique opportunity for patients with different stages of prostate cancer. 
2.3. 
Benefit/Risk Assessment 
The purpose of the PRO-MERIT trial is to test prostate cancer-associated antigens encoded in 
BNT112 for the first time in patients with different stages of prostate cancer. 
As of today, the RNA-LPX based cancer vaccines have been administered in more than 
270 patients with melanoma, triple negative breast cancer (TNBC), and human papilloma virus 
(HPV)+ cancers and demonstrated a favorable safety and tolerability profile in different 
indications, different treatment settings (metastatic, post neo-adjuvant, adjuvant) and with 
different types of cancer vaccine antigens. In these clinical trials, no dose-limiting toxicities 
(DLTs) were reported during dose escalation, the TEAEs considered related to trial drug were 
transient, mostly Grade 1 and 2, and likely associated with the specific format of encoding and 
delivering the vaccine antigens, namely single-stranded RNA formulated as a DOTMA (1,2-di-
O-octadecenyl-3-trimethylammonium propane)/DOPE (1,2-Dioleoyl-sn-glycero-3-
phosphoethanolamine) lipoplex. In summary, the class-intrinsic safety profile of RNA-LPX per 
se appears to be dominated by mild-to-moderate, transient and manageable influenza-like AEs. 
These AEs are expected based on the distinct range of cytokines released by RNA-LPX. In 
addition, transient lymphopenia (by sequestration) observed in laboratory examinations is 
expected to be mediated by Type 1 IFN.  
In addition to RNA-LPX class-intrinsic risks, potential risks related to the individual vaccine 
antigen targets are to be considered, which may potentially result in “on-target/off-tumor” 
toxicities mediated by the respective antigen-specific T cells. As the targets for the proposed 
prostate cancer trial were not used before in conjunction with the RNA-LPX format, the risk of 
on-target/off-tumor toxicity cannot be deduced from the ongoing trials. This risk is mitigated by 
selecting antigens with exquisitely cancer cell selective expression and lack of expression in vital 
normal tissues. The same pipeline has been used to select the cancer type specific vaccine 
antigens in the other ongoing RNA-LPX trials. Moreover, 2 of the 5 selected vaccine antigens 
have been used in trials by other sponsors in conjunction with other vaccine formats without 
indications of autoimmunity. Therefore, the risk of on-target/off-tumor toxicity is considered 
low. 
Given that the Good Laboratory Practice (GLP) toxicology studies did not identify a no observed 
adverse effect level, the maximum dose (i.e., 
µg total RNA) used safely in humans in the 
melanoma trials justifies the entire proposed dose range for the proposed trial. 
The planned trial will address in the safety program potential risks of both the vaccine format 
(considered low based on aggregate data from all RNA-LPX trials conducted by the sponsor), 
and immunopathology associated with T cells induced against the individual vaccine targets 
(considered low based on the sponsor’s ongoing clinical trials and cumulative data in the public 
domain from other vaccine trials).  
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Part 1 (dose titration) of the PRO-MERIT trial has been performed in the UK and Hungary and 
enrollment has been completed with 9 patients dosed. The SRC reviewed the available safety 
data for patients in Part 1 on 17 MAY 2021. The safety profile observed indicates that BNT112 
is a tolerable drug product with a manageable safety profile at the defined dose range (
to 
 µg) using the intra-patient step-up dose titration scheme. Observed AEs considered related 
to the IMP (including pyrexia, flu-like symptoms, hypertension, nausea, chills or headache), are 
in line with the innate immune activation by RNA-LPX, are transient in nature and manageable 
by analgesics, antipyretics or fluids at recommended and usual doses. The recommendation was 
to continue to Part 2 at the selected REDR (
µg) using the intra-patient step-up dose 
titration scheme. 
The annual review of safety data for the IB update occurred on 20 MAY 2021 (data extraction 
date) and included safety data from patients in Part 1 as well as Part 2. Neither the safety profile 
nor the benefit-risk assessment were changed. 
The sponsor’s ongoing Lipo-MERIT Phase 1 clinical trial in melanoma (NCT02410733) has 
provided promising signals for single agent and anti-PD-1 combination activity of RNA-LPX 
cancer vaccine against melanoma-shared antigens in pretreated checkpoint inhibitor-experienced 
patients with high medical need and limited treatment options. It has further demonstrated that in 
almost every patient the vaccine executes its MoA, inducing T cells against at least one of the 
antigens. A considerable fraction of these immune responses was strong (measurable ex vivo) 
and both new T cells were primed and pre-existing T cells were expanded. Responses were both 
CD8+, but also CD4+, indicating that effector T cells received cognate T cell help in the priming 
process. It is expected that, in particular for patients that are refractory to anti-PD-1 (meaning 
that activation of pre-existing memory T cells only is not sufficient to mediate clinical activity), 
combining the vaccine with anti-PD-1 (which would rescue newly primed T cells specificities 
from exhaustion) is synergistic. This expectation is supported by data from non-clinical 
experiments. 
Arm 1A and Arm 2 of the proposed clinical trial explores a combination of BNT112 and 
cemiplimab, anti-PD-1 antibody. Antibodies to PD-1/PDL-1 have been shown to be effective 
therapeutic options for cancer treatment. Cemiplimab is a fully human monoclonal antibody 
against PD-1 and is currently being evaluated in patients with advanced solid malignancies and 
B-cell lymphomas whose cancer are incurable and/or have failed to respond to or showed tumor 
progression despite standard therapy, or patients who are not candidates for standard therapy, or 
for whom no available therapy is expected to convey clinical benefit. Cemiplimab has 
demonstrated efficacy (based on ORR and DoR) and is approved in the U.S. for patients with 
advanced CSCC, NSCLC, and BCC. Patients in Arm 1b will be given the option to be treated 
with cemiplimab monotherapy after progression with BNT112 monotherapy. 
In addition to the potential safety risks, there is a potential unknown risk related to a delayed 
radical prostatectomy in patients with newly diagnosed LPC. In order to address this risk, 
patients will be followed for up to 12 months after the last dose of either IMP and the treating 
physicians will be able to adjust the treatment also during the course of the trial in case earlier 
intervention is needed.  
In summary, the potential benefits of the proposed trials include clinical responses and the 
generation of lasting T cells against prostate cancer TAAs both in BNT112 monotherapy and in 
combination with cemiplimab. This could potentially translate into clinically significant and 
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durable efficacy, which is of prime importance to patients and outweighs the potential risks 
outlined above. This warrants development of BNT112 in monotherapy and in combination with 
cemiplimab in patients with various stages of prostate cancer. 
Furthermore, the clinical data generated with the RNA-LPX cancer vaccines thus far in 
melanoma, TNBC and HPV+ cancers in monotherapy and in combination with anti-PD-1 
antibodies demonstrate a positive risk-benefit assessment and warrant further development of the 
RNA-LPX cancer vaccine in new indications, such as prostate cancer. The safety profile of 
cemiplimab is similar to the safety profile of other anti-PD-1/PD-L1. The important identified 
risks are immune-related AEs and injection-related reactions. Based on the currently available 
safety information for cemiplimab, safety information from other anti-PD-1 antibodies, the 
adequate risk identification and minimization described in the cemiplimab IB/protocols/ICFs, the 
emerging preliminary activity of cemiplimab on solid malignancies (including CSCC, NSCLC, 
and cervical cancer), the benefit-risk is considered favorable for continued clinical trials in these 
and other indications. 
For further information about the known and potential risks of BNT112 and cemiplimab, refer to 
the latest version of the respective IB (BNT112 or cemiplimab). 
3. 
Objectives and Endpoints 
Trial objectives and endpoints are listed in Table 3-1. 
 
Table 3-1: 
Objectives and endpoints of the clinical trial 
OBJECTIVES 
ENDPOINTS 
PRIMARY OBJECTIVE 
PRIMARY ENDPOINTS 
• 
(Part 1 and Part 2) Assess 
safety and tolerability profile of 
BNT112 monotherapy or in 
combination with cemiplimab 
• 
Occurrence of DLTs. 
• 
Occurrence of TEAEs reported by relationship, grade, and 
seriousness according to NCI CTCAE v5.0. 
• 
(Part 2 Arms 1a and 1b) 
Evaluate preliminary anti-
tumor activity of BNT112 
monotherapy and in 
combination with cemiplimab 
in patients with mCRPC based 
on ORR 
• 
ORR, defined as the number of patients with a CR or PR 
per PCWG329 as determined by the investigator as best 
objective response divided by the number of patients in the 
analysis set. 
SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
• 
Evaluate anti-tumor activity 
based on levels of PSA 
• 
PSA decline of 0 to 25%, >25% to 50%, and >50% 
compared to baseline. 
• 
PSADT post-treatment on C4D1 and D1 of every fourth 
subsequent cycle (e.g., C8D1, C12D1, etc.) in Part 1 and 
Part 2 Arm 1A and 1B, or on C4D1, C8D1, and EoT in 
Part 2 Arms 2 and 3 compared to baseline. 


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OBJECTIVES 
ENDPOINTS 
• 
PSA decline of ≥50% (according to the PCWG3). 
• 
(Part 1) Evaluate preliminary 
anti-tumor activity of BNT112 
monotherapy in patients with 
mCRPC based on ORR 
• 
ORR, defined as the number of patients with a CR or PR 
per PCWG329 as determined by the investigator as best 
objective response divided by the number of patients in 
the analysis set. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy or in combination 
with cemiplimab in patients 
with newly diagnosed LPC 
• 
Tumor response post-treatment compared to baseline. 
EXPLORATORY OBJECTIVES 
EXPLORATORY ENDPOINTS 
• 
Determine systemic 
induction/expansion of 
BNT112 antigen-specific 
T cells for BNT112 
monotherapy or in combination 
with cemiplimab  
• 
Occurrence of de novo induction or increase of BNT112 
antigen-specific T cells in peripheral blood under 
treatment on C3D15, and/or C8D15, EoT, or safety 
follow-up compared to baseline. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy and in 
combination with cemiplimab 
in patients with mCRPC 
• 
DoR, defined as the time from the first occurrence of a 
documented OR to the time of the first disease progression 
per PCWG329, as determined by the investigator, or death 
from any cause, whichever occurs first. 
• 
ORR and DoR, defined as above, using iRECIST.30  
• 
PFS, defined as the time from the first trial treatment to 
the first disease progression per PCWG3,29 as determined 
by the investigator, and per iRECIST30 determined by 
central reading, or death from any cause, whichever occurs 
first. 
• 
OS, defined as the time from first trial treatment until 
death from any cause. 
• 
Number of cycles received and RDI. 
• 
Evaluate preliminary anti-tumor 
activity of cemiplimab in 
patients with mCRPC who have 
been previously treated with, 
and who have progressed after 
BNT112 monotherapy 
• 
ORR, defined as the number of patients with a CR or PR 
per PCWG3 as determined by the investigator as best 
objective response divided by the number of patients in 
the analysis set. 
• 
DoR, defined as the time from the first occurrence of a 
documented OR to the time of the first disease progression 
per PCWG3, as determined by the investigator, or death 
from any cause, whichever occurs first. 
• 
ORR and DoR, defined as above, using iRECIST.  
• 
PFS, defined as the time from the first trial treatment to 
the first disease progression per PCWG3, as determined 


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OBJECTIVES 
ENDPOINTS 
by the investigator, and as per iRECIST determined by 
central reading, or death from any cause, whichever occurs 
first. 
• 
PFS2, defined as the time from the first trial treatment to 
the first disease progression after start of cemiplimab per 
PCWG3 as determined by the investigator, or death from 
any cause, whichever occurs first. 
• 
OS, defined as the time from first trial treatment until 
death from any cause. 
• 
Number of cycles received and RDI. 
• 
Assess safety and tolerability 
profile of cemiplimab 
monotherapy in patients 
following progression after 
BNT112 monotherapy 
• 
Occurrence of TEAEs reported by relationship, grade, and 
seriousness according to NCI CTCAE v5.0. 
• 
Evaluate preliminary anti-tumor 
activity of BNT112 
monotherapy or in combination 
with cemiplimab in patients 
with newly diagnosed LPC 
• 
PFS, defined as the time from the first trial treatment to 
the first disease progression per PCWG3 as determined by 
the investigator, or death from any cause, whichever 
occurs first. 
• 
OS, defined as the time from first trial treatment until 
death from any cause. 
• 
Preliminary assessment of 
biomarkers that might act as 
potential predictive, 
pharmacodynamics, anti-tumor, 
and safety indicators of activity 
of BNT112 monotherapy or in 
combination with cemiplimab  
• 
Status of tumor mutational burden and immune-related 
gene expression (at the RNA level) in tumor tissue prior to 
treatment. 
• 
Change in protein expression pattern/levels of tumor 
microenvironment markers (e.g., CD3, CD8, MHC-I, 
PD-L1, etc.) and prostate tumor markers (e.g., PSA, 
PSAP, NKX3-1, etc.) in tumor tissue post-treatment 
compared to baseline. 
• 
Baseline status or change in RNA target expression of 
BNT112–encoded antigens in the post-treatment tissue 
compared to baseline.  
• 
Change in T cell clonality/diversity post-treatment 
compared to baseline. 
• 
Changes in blood biomarkers prior to and during trial 
treatment. 
Abbreviations: AE = adverse event; C = Cycle; CR = complete response; CTCAE v5.0 = Common Terminology Criteria for 
Adverse Events, version 5.0; D = Day of cycle; DLT = dose-limiting toxicity; DoR = duration of response; EoT = End of 
Treatment; iRECIST = immune-modified Response Evaluation Criteria in Solid Tumors; MHC = major histocompatibility 
complex; NCI = National Cancer Institute; NKX3-1 = NK3 homeobox 1; OR = objective response; ORR = objective response 
rate; PCWG3 = Prostate Cancer Working Group 3; PD-L1 = programmed cell death 1 ligand 1; PFS = progression-free survival; 
PR = partial response; PSA = prostate-specific antigen; PSADT = prostate-specific antigen doubling time; PSAP = prostate-
specific acid phosphatase; RDI = relative dose intensity. 


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4. 
Trial Design 
4.1. 
 Overall Design 
The trial consists of 2 parts: Part 1 (dose titration) and Part 2 (dose expansion). Part 2 consists of 
four arms: Arms 1A and 1B (mCRPC patients) and Arms 2 and 3 (LPC patients). 
Part 1 contains a dose titration for initial safety assessment and identification of the 
recommended expansion dose range (REDR). It will enroll mCRPC patients to receive BNT112 
monotherapy at 3 predefined dose levels (DLs) until a discontinuation-of-treatment criterion is 
met (Section 7). Part 1 of the trial will employ a modified 3+3+3 design (adapted from Hamberg 
et al. 201013) with up to 9 evaluable patients. 
Once the REDR is defined, the trial will commence with Part 2 and enroll approximately 
106 patients in four arms (the expansion part, Section 4.2). Part 2 Arms 1A and 1B will enroll 
patients with mCRPC to receive BNT112 monotherapy or BNT112 in combination with 
cemiplimab, and Part 2 Arms 2 and 3 will enroll patients with newly diagnosed LPC eligible for 
treatment with ADT (e.g., goserelin acetate) to receive BNT112 monotherapy or BNT112 in 
combination with cemiplimab.  
Enrollment between Arms 1A and 1B in Part 2 and between Arms 2 and 3 will be randomized 
1:1 to avoid enrollment bias.  
The treatment in Part 2 Arms 1A and 1B will continue until a discontinuation-of-treatment 
criterion is met (Section 7). In Part 2 Arms 2 and 3 the treatment will be stopped at Cycle 8 
Day 1 (C8D1) or until a discontinuation-of-treatment criterion is met (Section 7). 
The safety of BNT112 in doses
 µg, 
 µg, and 
µg will be evaluated based on DLTs 
during the first treatment cycle (21 days) as well as the overall incidence of BNT112-related or 
potentially related TEAEs in both parts of the trial. The safety of concomitant administration of 
cemiplimab will be evaluated based on the overall incidence of cemiplimab-related or potentially 
related TEAEs in Part 2 Arms 1A and 2 of the trial and will follow the same rules as Part 1, until 
the SRC reviews and confirms that the combination safety profile is acceptable to continue with 
the enrollment for the combination arms. The safety will be evaluated by the SRC. For details, 
please refer to Section 9.6 and the SRC charter. 
The efficacy measurement in mCRPC patients (i.e., Part 1 and Part 2 Arms 1A and 1B) will be 
tumor response assessment by on-treatment imaging every 8 weeks (±7 days) for 24 weeks, and 
then every 3 months (±7 days) thereafter until a discontinuation-of-treatment criterion is met 
(Section 7) as assessed by the investigator. The Prostate Cancer Working Group 3 (PCWG3) 
criteria29 and immune-modified Response Evaluation Criteria in Solid Tumors (iRECIST) 
criteria30 will be used for endpoint response evaluation. If the investigator considers radiographic 
changes secondary to drug-induced inflammation and not to tumor progression, the investigator 
may postpone a diagnosis of PD until the next radiographic evaluation in the trial. 
Following progression after BNT112 monotherapy, patients in Arm 1B will have the option to be 
treated with cemiplimab monotherapy.  
The efficacy in LPC patients (i.e., Part 2 Arms 2 and 3) will be assessed by tumor measurement 
using mpMRI or MRI consistently throughout the trial. The same imaging modality should be 
used at screening and at all subsequent assessments. 
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Various blood- and tumor-based biomarkers will be analyzed in both parts. 
The trial will be conducted in approximately 30 trial centers in up to 5 countries.  
Trial periods are provided in the Schedule of Activities (SoA). 
4.1.1. 
Part 1 
Trial Part 1 will identify the REDR of BNT112 monotherapy in patients with histologically 
confirmed mCRPC who progressed after at least 2 but no more than 3 lines of life-prolonging 
systemic therapy (e.g., abiraterone or enzalutamide, docetaxel, cabazitaxel) or who cannot 
tolerate or have refused any of these therapies.  
Three doses of BNT112 cancer vaccine will be used for an intra-patient dose titration 
accommodating the inter- as well as intra-patient variability of the immune system activation: 
• DL1 [starting dose]:
µg of total RNA 
 µg of RNA of each antigen) 
• DL2 [intermediate dose]: 
µg of total RNA (
µg of RNA of each antigen)  
• DL3 [target dose]:
 µg of total RNA (
µg of RNA of each antigen)  
One additional DL of 
µg of total RNA (with 
 µg of RNA of each antigen) can be used 
for dose reductions (see Section 6.6.1). 
BNT112 will be given in the following dose schedule: D1, D8, and D15 of C1 and C2 and D1 
from C3 onwards. The individual dose titration will be conducted during C1 with DL1 on D1, 
DL2 on D8 and DL3 on D15. 
For the first 3 patients: (i) patients will be enrolled in a staggered manner with a safety 
monitoring interval of at least 1 week between the first and the second patient, and between the 
second and the third patient, and (ii) an overnight stay is required on C1D1, C1D8, and C1D15. 
On the 17 MAY 2021, the SRC recommended that patient monitoring can be limited to 4 to 6 h 
and no overnight stay is required. 
A minimum of 3 patients will be evaluated for a DLT assessment period defined as 1 cycle 
(21 days), see Section 6.6.1.1. At the discretion of the investigator, the dose of BNT112 may be 
maintained at the current DL for 1 dose, i.e., intra-patient dose titration may be delayed (see 
Section 6.6.1.1). For these patients, the DLT assessment period is extended to 28 days. 
The dose titration will be conducted according to the following rules (also refer to Table 4-1): 
• If none of the first 3 DLT evaluable patients in Part 1 experience a DLT at any given DL 
(i.e.,
µg,
µg, and 
µg), the REDR will be confirmed and Part 2 will be initiated. 
• If 1 of the first 3 DLT evaluable patients in the Part 1 experiences a DLT, 3 additional 
patients will be enrolled in Part 1. 
• If fewer than 2 of 6 DLT evaluable patients in Part 1 experience a DLT/DLTs (i.e., no 
additional DLTs in the last 3 patients), Part 2 will be initiated. 
• If 2 of the first 6 DLT evaluable patients in Part 1 experience a DLT, the cohort will be 
expanded to 9 patients. 
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• If 2 of the 9 DLT evaluable patients in Part 1 experience a DLT (no additional DLTs in 
the last 3 patients), Part 2 will be initiated.  
• If 3 or more of up to 9 DLT evaluable patients in Part 1 experience DLTs, accrual will be 
halted. In this case, the REDR will have been exceeded and dose titration will stop. 
However, an intermediate DL below the REDR may be explored. If the REDR is 
exceeded, the highest dose at which fewer than 3 DLT evaluable patients experience a 
DLT will be declared the REDR. 
In addition, if 2 or more patients in the first 3 patients cannot dose escalate to the target dose by 
C1D21 in the absence of a DLT, the cohort will be expanded to 6 patients (this situation will be 
regarded equivalent to an occurrence of 1 patient with DLT).  
Each patient may experience a maximum of 2 dose titration steps. The highest tolerated dose 
given during dose titration should then become the standard dose for that patient to be given for 
the remainder of the trial unless dose reduction is required.  
All patients will be closely monitored for TEAEs during the DLT assessment window. TEAEs 
identified as DLTs will be reported to the sponsor within 24 h. Any patient in Part 1 who does 
not complete the DLT assessment window for a reason other than a DLT will be considered non-
evaluable for the REDR assessment and may be replaced by an additional patient. Any patient 
who received < 3 doses of BNT112 during the first cycle for a reason other than a DLT will be 
considered non-evaluable for the REDR assessment and may be replaced by an additional 
patient. 
 
Table 4-1: 
Dose Titration Scenarios and Rules 
Dose (μg) 
0 DLT 
scenario 
1 DLT scenario 
2 DLT scenarios 
3 or more DLT 
scenarios 
0 
0 
0 
1 
0 
0 
2 
0 
1 
1 
> 2 DLTs across 
any DLs 
0 
0 
1 
0 
0 
2 
0 
1 
0 
1 
0 
1 
0 
0 
2 
0 
0 
1 
1 
0 
Total 
number of 
patients 
required 
3 
Go to 6 or 9 
9 
Action 
Move to 
expansion 
If 1/6 move to 
expansion; if additional 
DLT at any dose, go to 9 
If 2/9 go to expansion. 
If >2/9 then hold and go 
to SRC. 
If 2/9 move to expansion; if >2/9 then 
hold and go to SRC. 
Hold and go to 
SRC. 
Abbreviations: DLT = dose-limiting toxicity; SRC = Safety Review Committee. 
 
After DLT assessment has been completed in Part 1, safety data will be reviewed by the SRC to 
determine the REDR. The SRC may recommend, on the basis of emerging clinical safety, and 
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pharmacodynamics data from this trial, that other DLs and dosing schedule of BNT112 may be 
evaluated in the trial. 
4.1.2. 
Part 2 
Part 2 will further explore the safety and pharmacodynamics of BNT112 at the REDR in patients 
with mCRPC (Arms 1A and 1B) and LPC (Arms 2 and 3) and to evaluate the preliminary 
clinical response. In all arms, BNT112 will be given in the following dose schedule: D1, D8, and 
D15 of C1 and C2 and D1 from C3 onwards. The individual dose titration will be conducted 
during C1 with DL1 on D1, DL2 on D8 and DL3 on D15. The highest tolerated dose given 
during dose titration should be administered for the remainder of the trial unless dose reduction 
is required. The treatment will continue until a discontinuation-of-treatment criterion is met 
(Section 7). In Part 2 Arms 2 and 3 the treatment will be stopped at C8D1. 
Initially, patients will be monitored in the hospital overnight post-treatment at all visits in C1. On 
the 17 MAY 2021, the SRC recommended that patient monitoring can be limited to 4 to 6 h and 
no overnight stay is required. 
Part 2 Arms 1A and 1B (mCRPC) 
Approximately 66 (33 per arm) patients with histologically confirmed mCRPC, who progressed 
after at least 2 but no more than 3 lines of life-prolonging systemic therapy (e.g., abiraterone or 
enzalutamide, docetaxel, cabazitaxel) or who cannot tolerate or have refused any of these 
therapies will be enrolled in Part 2 Arms 1A and 1B. Enrollment between Arms 1A and 1B will 
be randomized 1:1 to avoid enrollment bias.  
Following progression after BNT112 monotherapy, patients in Arm 1B will have the option to be 
treated with cemiplimab monotherapy. 
Part 2 Arm 2 and Arm 3 (LPC) 
Treatment-naïve patients with LPC (i.e., N0, M0), defined according to European Association of 
Urology Guidelines on Prostate Cancer (2018)23 and in line with the U.S. National 
Comprehensive Cancer Network (NCCN 2020)35, who are eligible for treatment with ADT (e.g., 
goserelin acetate) followed by radical prostatectomy will be enrolled in Part 2 Arms 2 and 3. 
Enrollment between Arms 2 and 3 will be randomized 1:1 to avoid enrollment bias.  
4.2. 
Planned Number of Patients 
There will be 3 to 9 patients in Part 1 (dose titration part, single arm) and up to 106 patients in 
Part 2 (expansion part, four arms: up to 33 patients in Arm 1A and Arm 1B, respectively, and 
approximately 20 patients in Arm 2 and Arm 3, respectively). Drop-outs may be replaced. In 
total, there will be approximately 115 patients. 
Re-screening of patients is allowed. 
4.3. 
Trial Design Rationale 
This trial is designed to evaluate the safety, tolerability, immunogenicity, and preliminary 
efficacy of BNT112 in monotherapy and in combination with cemiplimab in mCRPC and LPC 
patients eligible for treatment with ADT (e.g., goserelin acetate) followed by radical 
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In Part 1, a modified 3+3+3 design (adapted from Hamberg et al. 201013) will be applied with 
approximately 3 to 9 patients enrolled. This modified 3+3+3 design is used to reduce the chance 
of incorrectly ceasing enrollment at a certain step-up DL, when inter- and intra-patient variability 
is expected and the true DLT rate may be <5%. If > 1 patient of the first 3 patients or > 2 patients 
of the first 6 patients experiences a DLT, no additional patients will be enrolled at that DL, in 
order to avoid patients being treated at DLs with unacceptable toxicities. Furthermore, intra-
patient dose titration is implemented and is justified in detail in the next section. 
Patients eligible for Part 1 and Part 2 Arms 1A and 1B of this trial will have histologically 
confirmed mCRPC and have progressed after at least 2 but no more than 3 lines of life-
prolonging systemic therapy (e.g., abiraterone or enzalutamide, docetaxel, cabazitaxel) or cannot 
tolerate or have refused any of these therapies. These lines of therapy include life-prolonging 
therapies administered in the metastatic hormone–sensitive setting. This description defines a 
population in which it is ethically acceptable and feasible to evaluate the safety, tolerability, 
immune response, and pharmacokinetics of novel therapies intended for the treatment of patients 
with advanced malignancies. 
Immune therapies based on antigen-specific T cells have the highest probability of success in 
patients with low tumor burden and at an early stage of the tumor’s life cycle. Therefore, patients 
eligible for Part 2 Arms 2 and 3 of this trial will have a newly diagnosed LPC and will be 
candidates for neoadjuvant treatment with LHRH agonist or antagonist followed by radical 
prostatectomy. LPC patients will be enrolled only after the initial safety assessment in the dose 
titration part of Part 1 is completed and the REDR is defined (for further details please also refer 
to Section 2.2).  
Both clinical trial populations were selected and refined together with clinical experts from the 
field to enable the real-life clinical setting where the benefit for the patients might be the highest. 
The clinical setting is further justified by several factors recognized as relevant and important for 
development of cancer vaccines, also listed in the FDA Guidance for Industry “Clinical 
Considerations for Therapeutic Cancer Vaccines”.34 These include the time to develop an anti-
tumor response, which is generally longer for immunotherapies, and the higher chance for a 
cancer vaccine to show efficacy in lower tumor burden patients and patients with limited prior 
therapy exposure. 
All patients in Part 2 Arms 2 and 3 will receive up to 3 DLs of BNT112 during the C1 intra-
patient dose titration based on the REDR defined in Part 1, thereby allowing for a safe 
combination with cemiplimab. The safety of this combination is further supported by data from 
the ongoing Lipo-MERIT trial where no differences were seen between RNA-LPX monotherapy 
and combination with anti-PD-1 or BRAF/MEK (serine/threonine-protein kinase B-Raf/mitogen-
activated protein kinase kinase) inhibitors. All combinations in that trial indicate a well-tolerated 
safety profile of these combinations with Lipo-MERIT vaccine doses ranging from
µg to 
µg. Safety of the treatment arms with BNT112 and cemiplimab combination will be 
reviewed and will follow the same rules as Part 1, until the SRC reviews and confirms that the 
combination safety profile is acceptable. Based on the recommendation from the SRC, the 
sponsor will decide if enrollment should continue for the combination arms. More details are 
provided in the SRC charter. 
Randomization in a 1:1 ratio between Part 2 Arms 1A and 1B and between Part 2 Arms 2 and 3 
is included to avoid enrollment bias. 
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Eligibility criteria are based primarily on clinical safety data from the Lipo-MERIT trial as well 
as standard eligibility criteria for mCRPC and LPC. 22, 25 Eligibility criteria for the Part 2 Arm 2 
(combination with cemiplimab) of the trial are, in addition, based on available safety data for 
cemiplimab as well as studies with anti-CTLA-4 and with anti-PD-1 treatments. 2, 37 
4.4. 
Dose and Schedule Rationale 
One of the purposes of early phase trials is to determine the optimal dose and schedule for a 
particular treatment. For classical chemotherapy and targeted agents, the highest tolerated dose 
will usually be the most effective and is often taken forward in later stage studies. For checkpoint 
inhibitors, the anti-tumor effect may reach a plateau after which an increased dose confers 
neither increased toxicity nor improved benefit. In contrast, for cancer vaccines, a maximum 
tolerated dose (MTD) is rarely reached, the effective range may be very broad, and there usually 
is some minimum threshold that elicits an immune response.9 The impact of antigen dose on 
immune response is controversial. A trial evaluating the immunologic response to high, medium, 
and low doses of a human epidermal growth factor receptor 2 (HER2)/neu intracellular domain 
protein-based vaccine showed differences in the kinetics of the expansion of an antigen-specific 
T cell response, but no difference in the overall magnitude of the T cell response, antibody 
response or avidity.12 There is evidence that different doses of peptide vaccines selectively 
stimulate expansion of T cells with different levels of avidity and cytotoxicity.20, 8 Moreover, the 
impact of different vaccine administration schedules on immune response has not been 
thoroughly explored. Most studies do not explore different vaccine dosing schedules and, 
therefore, the ideal vaccine dosing schedule has not been identified. The dose titration part as 
well as the expansion cohorts will investigate potential large differences in immune response and 
preliminary anti-tumor efficacy of DLs below the MTD/maximum administered dose alone or in 
combination with ADT (e.g., goserelin acetate) with or without cemiplimab in order to inform 
dose and schedule in pivotal studies. 
BNT112: The proposed starting dose and dosing schedule of BNT112 as a single agent is based 
primarily on the safety, immunogenicity, preliminary efficacy, and generated in the ongoing 
clinical trials with the sponsor’s RNA-LPX as well as on an integrated assessment of the 
proposed MoA (i.e., generation of a T cell response to a tumor shared antigen), efficacy in 
murine tumor models, and in vivo safety in the GLP toxicity studies conducted in mice.  
Based on preliminary analysis of safety, efficacy and immunogenicity data of the Lipo-MERIT 
trial as well as the other ongoing Phase 1 clinical trials, a dose range of
, and 
µg was 
proposed to be tested in the Part 1 dose titration part of this trial. 
The step-up dose titration follows the approach implemented in the ongoing clinical trials with 
RNA cancer vaccine IMPs and allows for optimal dose management on an individual basis, and 
accounts for inter- and intra-individual variability of the immune system. Step-up dosing may 
offer advantages over flat dosing, including the potential mitigation of a hypothetical first dose 
phenomenon (i.e., allowing the patient to acclimate to gradually increasing doses of BNT112) 
with the lower starting dose acting as a “lead-in” dose potentially mitigating immune system 
activation-related AEs. This approach was confirmed in the previous and ongoing sponsor trials 
with RNA-encoded cancer vaccines. The dosing schedule proposed in this trial is based primarily 
on the Lipo-MERIT trial (6 weekly vaccinations followed by 2 bi-weekly vaccinations followed 
by continuous treatment with the maximum individually tolerated dose given every 28 days for 
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patients without PD). The dosing schedule in the proposed prostate cancer trial includes the 
intensified weekly dosing in C1 and C2 followed by the treatment with the maximum 
individually tolerated dose every 21 days. The schedule also fits the dosing schedule for 
cemiplimab (every 21 days) and both are easily incorporated in the standard dosing of the ADT 
(e.g., goserelin acetate is given Q12W). 
Part 1 (dose titration) of the PRO-MERIT trial has been performed in the UK and Hungary and 
enrollment has been completed with 9 patients dosed. The SRC reviewed the available safety 
data for patients in Part 1 on 17 MAY 2021. The safety profile observed indicates that BNT112  
a tolerable drug product with a manageable safety profile at the defined dose range 
µg) using the intra-patient step-up dose titration scheme. Observed AEs considered related to the 
IMP (including pyrexia, flu-like symptoms, hypertension, nausea, chills or headache), are in line 
with the innate immune activation by RNA-LPX, are transient in nature and manageable by 
analgesics, antipyretics or fluids at recommended and usual doses. The recommendation was to 
continue to Part 2 at the selected REDR (
to 
 µg) using the intra-patient step-up dose 
titration scheme. The annual review of safety data for the IB update occurred on 20 MAY 2021 
(data extraction date) and included safety data from patients in Part 1 as well as Part 2. Neither 
the safety profile nor the benefit-risk assessment were changed. 
Cemiplimab is given at a dose of 
 mg as an IV infusion over 30 minutes every 3 weeks. 
Goserelin acetate is administered at a dose of 10.8 mg as an SC injection into the anterior 
abdominal wall Q12W, according to the current SmPC (e.g., Zoladex® LA 10.8 mg implant).3 In 
order to facilitate interpretation of toxicities with suspected relationship to the IMP, goserelin 
acetate is to be administered anytime within 7 days prior to the start of BNT112 treatment. In 
case another ADT is used, it is to be administered in line with the current prescribing information 
valid in a given country. 
4.5. 
End of Trial Definition 
The end of the trial is defined as the date of last patient contact, whether in-person or by phone, 
for the last patient in the trial globally, including the efficacy follow-up for 12 months after the 
last dose of trial treatment. 
In addition, the sponsor may decide to terminate the trial at any time. If the sponsor decides to 
terminate the trial, patients who are still receiving trial treatment or undergoing survival follow-
up may be enrolled in an extension trial or a non-interventional trial, if available 
(Section 10.1.9). 
5. 
Trial Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Each potential participant must fulfill all of the following criteria to be enrolled in the trial. 
1. Patients must be male and aged ≥18 years. 
2. Patients must have histologically confirmed prostate adenocarcinoma. 
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3. Patients or their legally authorized representative (if applicable) must sign an ICF 
indicating that they understand the purpose of the procedures required for the trial and are 
willing to participate. 
4. Patients must have an ECOG PS score of 0 or 1.  
5. Patients must have adequate organ and bone marrow function, defined as:  
a. Bone marrow/hematological function:  
− Absolute neutrophil count (ANC) ≥1.5 × 109/L.  
− Hemoglobin ≥9.0 g/dL. No transfusion is allowed within 2 weeks prior to trial 
treatment initiation.  
− Platelet count ≥100 × 109/L. 
b. Coagulation status: 
− International normalized ratio ≤1.5 ULN. Unless on therapeutic anticoagulants 
with values within therapeutic window. 
c. Renal function: 
− Glomerular filtration rate ≥45 mL/min/1.73 m² according to the abbreviated 
Modification of Diet in Renal Disease equation. 
6. Patients who are sexually active with a woman of childbearing potential must agree to 
use a condom with spermicidal foam/gel/film/cream/suppository in addition to at least 
one form of highly effective contraception used by the patient or their partner (for details, 
see Section 10.4) during the trial starting after signing the ICF and for 90 days after 
receiving the last dose of BNT112 OR for 6 months after receiving the last dose of 
cemiplimab. 
7. Patients should not donate sperm during the trial starting after signing the ICF and for 
90 days after receiving the last dose of BNT112 OR for 6 months after receiving the last 
dose of cemiplimab. 
8. Patients must be willing and able to adhere to the prohibitions and restrictions specified 
in this protocol.  
In addition to the above inclusion criteria, the following are mandatory for the different treatment 
arms: 
Specific inclusion criteria for mCRPC patients (Part 1 and Part 2 Arms 1A and 1B) 
9. Patients must have histologically confirmed mCRPC and have progressed after at least 2 
but no more than 3 lines of life-prolonging systemic therapy (e.g., abiraterone or 
enzalutamide, docetaxel, cabazitaxel) or cannot tolerate or have refused any of these 
therapies. These lines of therapy include life-prolonging therapies administered in the 
metastatic hormone–sensitive setting.  
10. Prior surgical or chemical castration with a serum testosterone <1.7 nmol/L (50 ng/dL). If 
the method of castration is luteinizing hormone-releasing hormone analogue (LHRHa), 
there must be a plan to maintain effective LHRHa therapy for the duration of the trial. 


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11. Patients must have documented mCRPC progression within 6 months prior to screening 
(assuming no subsequent change in treatments), as determined by the investigator, by 
means of 1 or more of the following criteria: 
a. PSA progression as defined by a minimum of 2 rising PSA levels with an interval 
of ≥1 week between each assessment where the PSA value at screening should be 
>2 ng/mL. 
b. Two rises out of 3 PSA sequential tests separated by at least 1 week also satisfies 
the criteria for baseline progression providing a new nadir is not established (i.e., 
upward trend) – see Section 10.9. 
c. Radiographic disease progression in soft tissue based on modified Response 
Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) with or without 
PSA progression. 
d. Radiographic disease progression in bone defined as the appearance of 2 or more 
new bone lesions on bone scan with or without PSA progression. 
12. Patients must have adequate liver function defined as:  
a. Total bilirubin <1.5 × ULN (≤3 × ULN is acceptable for patients with known 
Gilbert disease). 
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5 × ULN.  
− For patients with hepatic metastases, total bilirubin <3 × ULN and AST or 
ALT <5 × ULN are acceptable. 
− For patients with bone metastases, alkaline phosphatase <5 × ULN and 
albumin ≥2.5 g/dL are acceptable.  
13. Patients must agree to provide an archival pre-treatment formalin-fixed, paraffin-
embedded tumor sample if available. 
Specific inclusion criteria for newly diagnosed LPC patients (Part 2 Arms 2 and 3)  
14. Treatment-naïve patients with LPC (i.e., N0, M0). According to risk levels of the 
European Association of Urology Guidelines on Prostate Cancer (2018)24 and in line with 
the US National Comprehensive Cancer Network (NCCN 2020)35 patients must have at 
least one of the following:  
a. PSA >20 ng/mL or 
b. Gleason Score >7 or 
c. Localized stage ≥cT2c, N0, M0 according to tumor, node, metastasis (TNM) 
classification7  
15. Patients who intend to have and are suitable for a radical prostatectomy. 
16. Patients must have adequate liver function defined as: 
a. Total bilirubin ≤1.5 × ULN (≤3 × ULN is acceptable for patients with known 
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b. AST and ALT ≤2.5 × ULN 
17. Patients must agree to provide tumor sample(s) from pre-treatment diagnostic biopsy and 
planned post-treatment surgery. 
18. Patient must be eligible for up to 6 months of ADT treatment before prostatectomy. 
5.2. 
Exclusion Criteria  
Each potential participant is not eligible to be included in the trial if any of the following criteria 
at screening to be enrolled in the trial. In addition, all lab criteria must be fulfilled within 7 days 
prior to starting IMP. 
Medical Conditions 
1. Patients with uncontrolled intercurrent illness, including but not limited to: 
a. Ongoing or active infection which requires systemic treatment with antibiotics or 
corticoid therapy within 14 days before the first dose of IMP. 
b. Symptomatic congestive heart failure (Grade III or IV as classified by the New 
York Heart Association), myocardial infarction within 3 months before screening, 
unstable angina pectoris, or cardiac arrhythmia. 
c. Known recent history (in the past 5 years) or presence of significant pulmonary 
conditions such as uncontrolled chronic lung disease, or any evidence of 
interstitial lung disease, or active, non-infectious pneumonitis. 
d. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or 
diastolic blood pressure ≥100 mmHg, despite optimal medical management. 
e. Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, 
T-cell negative severe combined immunodeficiency [SCID]) or combined T- and 
B-cell immunodeficiencies (e.g., T- and B-cell negative SCID, Wiskott- Aldrich 
syndrome, ataxia telangiectasia, common variable immunodeficiency). 
f. Ongoing or recent evidence (within the past year) of significant autoimmune 
disease that required treatment with systemic immunosuppressive treatments 
which may suggest risk for immune-related AEs. 
Note: Patients with autoimmune-related hyperthyroidism, autoimmune-related 
hypothyroidism who are in remission, or on a stable dose of thyroid-replacement 
hormone, vitiligo, or psoriasis may be included. 
g. Non-healing wound, skin ulcer (of any grade), or bone fracture. 
h. Patients with prior allogeneic stem cell or solid organ transplantation. 
i. Patients with the following risk factors for bowel perforation (e.g., history of 
acute diverticulitis or intra-abdominal abscess in the last 3 years; history of 
gastrointestinal obstruction or abdominal carcinomatosis). 
j. Patients with uncontrolled type 1 diabetes mellitus.  
Note: Patients controlled on a stable insulin regimen are eligible. 
k. Patients with uncontrolled adrenal insufficiency. 


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l. Any other disease, metabolic dysfunction, physical examination finding, and/or 
laboratory finding giving reasonable suspicion of a disease or condition that 
contraindicates the use of an investigational drug or may render the patient at 
high-risk for treatment of complications. 
2. Patients with a known history or current malignancy other than the inclusion diagnosis. 
Note: Exceptions are patients with malignancies with a negligible risk of metastasis or 
death, that have been adequately treated, such as non-invasive basal cell or non-invasive 
squamous cell skin carcinoma, non-invasive, superficial bladder cancer, and any cancer 
with a complete response (CR) that lasted more than 2 years may be included. 
3. Patients who have had a splenectomy. 
4. Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks 
before screening, or have not fully recovered from surgery, or have a surgery planned 
during the time of trial participation, except for the radical prostatectomy planned for 
patients in Part 2 Arms 2 and 3.  
5. Patients who have a known history of any of the following: 
a. HIV 1 or 2 
b. Hepatitis B (carrier or active infection) 
c. Hepatitis C (unless considered cured 5 years post curative anti-viral therapy) 
6. Patients with a known allergy, hypersensitivity, or intolerance to BNT112 or its 
excipients (all patients in Parts 1 and 2), cemiplimab or its excipients (patients in Part 2 
Arm 1A, Arm 1B switch-over patients, and Arm 2 only), or to ADT (e.g., goserelin) or 
excipients thereof (patients in Part 2 Arms 2 and 3 only). 
7. Patients with any condition for which, in the opinion of the investigator, participation 
would not be in the best interest of the patient (e.g., compromise the well-being) or that 
could prevent, limit, or confound the protocol-specified assessments. 
8. In situations where trial patients are not legally competent to provide consent (e.g., 
mentally incapacitated), these patients are not allowed to enter the trial. 
Prior/Concomitant Therapy 
9. Patients who have received or currently receive the following therapy/treatment:  
a. Chronic systemic immunosuppressive corticosteroid treatment (prednisone >5 mg 
daily PO or IV, or equivalent) during the trial. 
Note: Replacement therapy (e.g., physiologic corticosteroid replacement therapy 
for adrenal or pituitary insufficiency) is not considered a form of systemic 
treatment and is permitted. 
b. Prior treatment with other immune-modulating agents that was (a) within fewer 
than 4 weeks (28 days) or 5 half-lives (whichever is longer) prior to the first dose 
of cemiplimab, or (b) associated with immune-mediated AEs that were Grade ≥1 
within 90 days prior to the first dose of cemiplimab, or (c) associated with toxicity 
that resulted in discontinuation of the immune-modulating agent. 


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c. Prior treatment with other immune-modulating agents for any non-cancer disease 
within 4 weeks or 5 half-lives of the agent (whichever is longer) before the first 
dose of IMP. 
d. Prior treatment with live-attenuated vaccines within 4 weeks before the first dose 
of IMP and during treatment with IMP. 
e. Prior treatment with an investigational drug (including investigational vaccines) 
within 4 weeks or 5 half-lives of the agent (whichever is longer) before the 
planned first dose of IMP.  
f. Therapeutic PO or IV antibiotics within 14 days prior to enrollment.  
Note: Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary 
tract infection or chronic obstructive pulmonary disease) may be enrolled. 
g. Concurrent use of herbal products that may decrease PSA levels (e.g., saw 
palmetto). 
Other Exclusion Criteria for All Patients 
10. Patients who have previously been enrolled in this trial. 
11. Patients with substance abuse or known medical, psychological, or social conditions that 
may interfere with the patient’s participation in the trial or evaluation of the trial results. 
12. Patients affiliated with the investigational site (e.g., a close relative of the investigator or 
dependent person, such as an employee or student of the investigational site). 
Specific Exclusion Criteria for mCRPC Patients (Part 1 and Part 2 Arms 1A and 1B) 
Excluded medical conditions  
13. Patients with toxicities from previous anti-cancer therapies that have not resolved to 
baseline levels or to Grade ≤1 according to NCI CTCAE v5.0 with the exception of 
alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral 
neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy must 
have recovered to Grade ≤2.  
14. Patients with clinically active brain metastases.  
a. Patients with a history of symptomatic metastatic brain or meningeal tumors may 
be included, if the end of definitive therapy is >3 months before the first dose of 
BNT112 and the patients have no clinical or radiological evidence of tumor 
growth. 
b. Patients with brain metastases must not be undergoing acute or chronic 
corticosteroid therapy or steroid taper.  
c. Patients with central nervous system symptoms should undergo a CT scan or MRI 
of the brain to exclude new or progressive brain metastases. Spinal cord 
metastasis is acceptable. However, patients with spinal cord compression should 
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Excluded prior or concomitant anti-cancer therapies  
15. Patients who have received or currently receive the following anti-cancer therapy/agent: 
a. Prior radiation therapy with curative intent within 14 days before the first dose of 
IMP. 
Note: Palliative radiotherapy is allowed. 
b. Prior treatment with an anti-cancer agent (within 4 weeks or for systemic 
therapies after at least 5 half-lives of the drug [whichever is longer] before the 
first dose of IMP). 
Note: Prior treatment with bone resorptive therapy, such as bisphosphonates 
(e.g., pamidronate, zoledronic acid, etc.) and denosumab, is allowed assuming 
that the patients have been on stable doses for ≥4 weeks prior to first dose of trial 
treatment. 
c. Prior treatment with anti-cancer immunomodulating agents, such as blockers of 
PD-1, PD-L1, tumor necrosis factor receptor superfamily member 9 (TNRSF9, 
4-1BB, CD137), OX-40, therapeutic vaccines, cytokine treatments, or any 
investigational agent within 4 weeks or 5 half-lives (whichever is longer) before 
the first dose of IMP. 
Specific exclusion criteria for LPC patients (Part 2 Arms 2 and 3) 
16. Patients who are expected to be unable to undergo an mpMRI or MRI. 
5.3. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical trial but are not 
subsequently entered in the trial. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure patients to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious AE (SAE). 
Patients who do not meet the criteria for participation in this trial (screen failures) may be 
rescreened.  


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6. 
Trial Treatment 
Trial treatment is defined as any investigational treatment(s), marketed product(s), or placebo 
intended to be administered to a trial patient according to the trial protocol. 
(If applicable) NIMP ADT is to be administered first, thereafter BNT112, and then cemiplimab. 
 
Investigational medicinal products (IMPs): 
IMP 1: 
BNT112 (previously referred to as W_pro1 in this and other trial-related 
documentation) 
Composition: 
BNT112 consists of messenger RNA (mRNA; further referred to as RNA) targeting 
5 antigens expressed in de novo and metastatic prostate cancer that are separately 
complexed with liposomes to form serum-stable RNA lipoplexes 
Administration: Five slow IV bolus injections per administration (i.e., one injection per each antigen 
followed by a saline flush and separated from the next injection by at least 
5 minutes) 
Dosage 
regimen: 
One cycle (C) is defined as 21 days 
The patients will receive the following treatments in the following dose and 
schedule:  
Part 1 and Part 2 Arms 1A and 1B (mCRPC) 
• 
IV administration of BNT112 on Day (D)1/8/15 of C1 (intra-patient dose 
titration) and C2, thereafter starting with D1 of C3 every 3 weeks (Q3W) 
until end of treatment criterion is met 
• 
Part 1/Dose Titration 
- 
Three doses of BNT112 will be used for an intra-patient dose titration 
during C1:
µg,
µg, and 
µg of total RNA, comprising
µg, 
 µg, and
µg of RNA of each of the 5 antigens encoded by 
BNT112, respectively. 
• 
Part 2/Expansion 
- 
REDR was selected after the review of individual and cumulative 
safety data, and preliminary pharmacodynamic data of Part 1 by the 
SRC. The selected dose range consists of a starting first dose of 
BNT112 of
µg, with an intra-patient dose titration to 
µg in the 
second dose, and 
 µg of total RNA in the next doses. Total RNA 
of
µg,
µg and
µg comprise
µg, 
µg, and
µg of RNA 
of each of the 5 antigens encoded by BNT112, respectively 
- 
Part 2 Arm 1A: Cemiplimab 
mg IV Q3W 
- 
Part 2 Arm 1B: following progression after BNT112 monotherapy, 
patients will have the option to be treated with cemiplimab 
 mg 
IV Q3W monotherapy 
 
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Part 2 Arms 2 and 3 (LPC) – Part 2/Expansion ONLY 
• 
IV administration of BNT112 on D1/8/15 of C1 (intra-patient dose titration) 
and C2, thereafter starting with D1 of C3 in a Q3W schedule until C8 
followed by radical prostatectomy 
• 
Part 2 Arm 2: Cemiplimab
mg IV Q3W 
Duration of 
treatment: 
• 
Part 1 and Part 2 Arms 1A and 1B (mCRPC): The treatment with BNT112 
will last until unacceptable toxicity or disease progression 
• 
Part 2 Arms 2 and 3 (LPC): The treatment with BNT112, cemiplimab will 
last until unacceptable toxicity or disease progression, or up to C8 
• 
If either BNT112 or cemiplimab needs to be discontinued, treatment with 
either cemiplimab or BNT112 can continue upon investigator and sponsor 
agreement 
• 
If treatment with ADT (e.g., goserelin acetate) needs to be discontinued, 
cemiplimab and/or BNT112 also need(s) to be discontinued 
IMP 2: 
Cemiplimab (LIBTAYO) 
Composition: 
Programmed death receptor-1 (PD-1) blocking antibody 
Dosage regimen 
and duration of 
treatment: 
Refer to above description of IMP1 for dosage regimen and duration of treatment 
Non-investigational medicinal product (NIMP): 
Part 2 Arms 2 and 3 (LPC) 
ADT, e.g., Goserelin acetate subcutaneous (SC) injection at a dose of 10.8 mg every 12 weeks or other 
ADT according the current prescribing information valid in a given country. 
Product: 
Goserelin acetate (Zoladex® LA 10.8 mg implant) 
Composition: 
Goserelin acetate (equivalent to 10.8 mg goserelin) 
Administration: SC 
Dosage 
regimen: 
One 10.8 mg depot injection given into the anterior abdominal wall every 12 weeks 
(Q12W) 
Duration of 
treatment: 
Two injections (C1D1 and C5D1); treatment will last until unacceptable toxicity or 
disease progression, or up to C8 
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Figure 6-1: 
Treatment Administration – Part 1 and Part 2 
 
 
Abbreviations and Footnotes: 
LPC = localized prostate cancer; mCRPC = metastatic castration resistant prostate cancer; Q3W = every three 
weeks. 
& 
Recommended dose range (REDR) is confirmed in Part 1. 
* 
Maximum administered dose 
µg; minimum administered dose 
µg; no dose re-escalation allowed. 
# 
In combination with ADT (e.g., Goserelin). 
$ 
From Day 1 of C1 onward, each patient will receive the individual standard dose (or the highest tolerated dose 
from Cycle 1) at each BNT112 administration. 
% 
Following progression after BNT112 monotherapy, patients in Arm 1b will have the option to be treated with 
cemiplimab monotherapy
 mg IV Q3W. 
 
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6.1. 
Trial Treatments Administered 
The details of BNT112 (test product) are presented in Table 6-1. 
 
Table 6-1: 
Identity and Properties of IMP1: BNT112 (IMP) 
Generic name/INN (brand name): 
Not applicable 
Substance code name: 
BNT112 
Formulation:  
Injectable solution 
Route of administration: 
IV injection 
Composition: 
Active ingredients 
Five RNA-encoded prostate cancer-specific antigens 
Strength (amount of drug per unit): 
mg/mL of RNA of each antigen in a single use vial 
Concentration after appropriate 
dilution: 
Individually diluted with isotonic sodium chloride and complexed with 
liposomes to form RNA-LPX products 
Storage conditions: 
RNA drug products must be stored at –20±5°C (further descriptions 
are given in the current Pharmacy Manual) in a locked area with 
restricted access and handled in accordance with the manufacturer’s 
instruction.  
Liposomes and NaCl solution must be stored at 5±3°C. 
Marketing authorization holder: 
Not applicable 
Abbreviations: INN = international nonproprietary name; IV = intravenous; RNA = ribonucleic acid; 
RNA-LPX = RNA-lipoplex. 
 
The details of the PD-1 blocking antibody cemiplimab (concomitant IMP) are presented in 
Table 6-2. 
 
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Table 6-2: 
Identity and Properties of IMP2: Cemiplimab 
Generic name/INN (brand name):  
Cemiplimab (Libtayo) 
Class:  
PD-1 blocking antibody 
Formulation:  
Liquid in vial 
Route of administration: 
IV 
Composition: 
Active ingredient: 
Cemiplimab
 mg/mL and 
mg/mL DP are formulated in an 
aqueous buffered solution at pH 6.0 
Other ingredients: 
10 mM histidine, 5% (w/v) sucrose, 1.5% (w/v) L proline, and 
0.2% (w/v) polysorbate 80. 
Strength (amount of drug per unit): 
 mg/7 mL (
mg/ml) 
Storage conditions: 
Must be stored at 2°C to 8°C. 
Marketing authorization holder: 
Regeneron Ireland DAC. 
Abbreviations: INN = international nonproprietary name. 
 
The details of the LHRH agonist goserelin acetate (NIMP) are presented in Table 6-3.  
 
Table 6-3: 
Identity and Properties of NIMP: Goserelin Acetate 
Generic name/INN (brand name): 
Goserelin acetate (e.g., Zoladex® LA 10.8 mg implant) 
Class: 
LHRH agonist (gonadotropin releasing hormone analogue) 
Formulation:  
Implant (depot) 
Route of administration: 
Deep SC injection into the anterior abdominal wall below the 
navel line 
Composition: 
Active constituent 
goserelin acetate equivalent to 10.8 mg goserelin per depot 
Other Constituents  
Lactide-glycolide copolymer to total weight 36.0 mg per depot 
Strength (amount of drug per unit): 
10.8 mg goserelin in pre-filled sterile ready-to-use syringe a 
Storage conditions: 
Do not store above 25 °C 
Marketing authorization holder: 
Astra Zeneca UK Limited (Luton, LU1 3LU, UK) 
Abbreviations: INN = international nonproprietary name; LHRH = luteinizing hormone-releasing hormone; 
UK = United Kingdom; SC = subcutaneous. 
a Zoladex® LA 10.8 mg implant is supplied as a single dose SafeSystem™ syringe applicator with a protective 
sleeve in a sealed pouch which contains a desiccant. 
 
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6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
IMP 1 - BNT112 
For instructions on dilution of the IMP BNT112, stability of the diluted solution, and 
administration details, please refer to the Pharmacy Manual provided in the Pharmacy Trial File.  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all BNT112 received and any discrepancies are reported and 
resolved before use of the supplied BNT112. Only patients enrolled in the trial may receive 
BNT112 and only authorized site staff may supply or administer BNT112. All BNT112 must be 
stored in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for BNT112 accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused IMP are provided in the 
trial-related Pharmacy Manual. 
6.2.2. 
IMP 2 - Cemiplimab 
Based on data from ongoing long-term, accelerated, and stress stability studies, the cemiplimab 
IMP is considered stable for use. 
Cemiplimab IMP must be stored at the trial centers at 2°C to 8°C. The temperature of storage in 
the refrigerator should be checked and recorded at least daily as prescribed in the Pharmacy 
Manual.  
Details on storage and preparation for cemiplimab IMP for IV administration are provided in the 
Pharmacy Manual. 
Storage of the infusion solution: cemiplimab IMP should be stored at room temperature (≤25°C 
for no more than 8 h from the time of preparation to the end of infusion, or at 2°C to 8°C for no 
more than 24 h from the time of preparation to the end of infusion. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
At screening, patients will be assigned a unique number (patient identification code), regardless 
of whether they actually receive trial treatment.  
In Part 2, patients with mCRPC treated in Arm 1A or Arm 1B, and patients with LPC treated in 
Arm 2 or Arm 3, will be randomized in 1:1 ratio. Central randomization will be used to reduce 
potential investigator bias. 
The site will contact the central randomization service prior to the start of trial treatment 
administration for each patient. The treatment assignment will be recorded on the applicable 
electronic case report form (eCRF), as required.  
6.4. 
Trial Treatment Compliance 
Patients will receive trial treatment 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 


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source documents and recorded in the eCRF. The dose of trial treatment and trial patient 
identification will be confirmed at the time of dosing by a member of the trial center staff other 
than the person administering the trial treatment.  
6.5. 
Concomitant Therapy 
Any background therapy for cancer or concomitant diseases/disorders not defined as NIMP and 
any non-drug cancer treatment (e.g., palliative radiotherapy/any supportive treatment) that is 
ongoing at the time of first IMPs administration (C1D1) or newly started after C1D1 is defined 
as concomitant treatment. Administration of concomitant treatment must be reported in the 
appropriate section of the eCRF.  
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
adequate supportive care except for those medications identified as “prohibited” (Section 6.5.2). 
• Palliative radiotherapy during the trial will be allowed for local pain control provided that 
(i) in the opinion of the investigator, the patient does not have PD AND (ii) no more than 
10% of the patient’s bone marrow is irradiated AND (iii) the radiation field does not 
encompass a target lesion. 
• Granulocyte-colony stimulating factor and other hematopoietic growth factors may be 
used in the management of acute toxicity, such as febrile neutropenia, when clinically 
indicated or at the investigator’s discretion.  
• Blood cell transfusion is allowed during the trial if clinically indicated. No transfusion is 
allowed within 2 weeks prior to trial treatment initiation. 
• Steroid treatment is permitted to modulate symptoms of an immune-related AEs at the 
discretion of the investigator. Replacement therapy (e.g., thyroxine, insulin, or 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is 
permitted. However, whenever possible corticosteroid treatment (prednisone >5 mg daily 
PO or IV, or equivalent) should be avoided as it counteracts with the MoA of the vaccine. 
• Bisphosphonates (e.g., pamidronate, zoledronic acid, etc.) and denosumab. 
• Multivitamins, vitamin D, calcium, and supplements in prevention of weight loss. 
• For further details, please refer to the SoA: Section 1.3 (Part 1 and Part 2 Arms 1A 
and 1B), Section 1.4 (Part 2 Arms 2 and 3), and Section 1.5 (Part 2 Arm 1B [switch-over 
patients]). 
6.5.1. 
Treatment of AEs Related to Treatment with BNT112 based on the RNA-LPX 
Class Profile 
The class-intrinsic safety profile of RNA-LPX per se appears to be dominated by mild-to-
moderate, transient and manageable influenza-like drug-related AEs (i.e., ADRs). The AEs are 
manageable by analgesics or antipyretics at recommended commonly used doses. Treatment of 
these events is dependent on the discretion of the treating physician with treatment suggestions 
provided below. 
• Treat fever with acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) with 
a dose per institution’s recommendation. 


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• After the first occurrence of influenza-like symptomatology, patients can be 
premedicated with standard therapeutic dose of acetaminophen, or NSAIDs, at least 
60 minutes before BNT112 administration followed by a second dose 5 to 8 h after 
BNT112. 
• Corticosteroid treatment (prednisone >5 mg daily PO or IV, or equivalent) should be 
avoided as either prophylaxis or treatment as it counteracts the effects of BNT112. 
• Ensure adequate hydration of patients on the day of BNT112 administration. Consider 
administering IV isotonic fluid (e.g., normal saline 500 to 1000 mL) within 
approximately 1 h following the dose of BNT112 per institutional standard. 
In addition to clinically manifested AEs described above, a transient reversible lymphopenia is 
mentioned above which was observed in laboratory examinations – there is no clinical 
manifestation of this event and no treatment required. 
For further information about the known and potential risks of BNT112 refer to the latest version 
of the IB.  
6.5.2. 
Prohibited Concomitant Therapy 
The following concomitant therapies and medications are not allowed from C1D1 until the 
Safety Follow-Up (FU)-D30 visit (for Part 1 and Part 2 Arm 1B and Arm 3) and from C1D1 
until Safety FU-D90 visit (for Part 2 Arm 1A, Arm 1B switch-over patients, and Arm 2): 
• Any concomitant systemic anti-cancer therapy defined as any agent or combination of 
agents with clinically proven antineoplastic activity that achieves non-negligible systemic 
bioavailability after being administered by any route for affecting the malignancy, either 
directly or indirectly, including palliative and therapeutic objectives except for the 
concomitant use of cemiplimab (Part 2 Arms 1A and 2) and ADT (e.g., goserelin acetate) 
(Part 2 Arms 2 and 3). 
• Immunosuppressive or maintenance therapy with systemic corticosteroids (PO or IV 
prednisone > 5 mg per day, or its equivalent) unless required per investigator’s 
decision.  
• Note: Replacement therapy (e.g., physiologic corticosteroid replacement therapy for 
adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is 
permitted. 
• Immunization with live-attenuated vaccines within 28 days prior to the first dose of IMP 
and during treatment with IMP. In addition, patients should not receive any live-
attenuated vaccines within 3 months after the last dose of IMP. 
• Use of herbal products that may decrease PSA levels (e.g., saw palmetto). 
If a patient receives any of these during the trial, the sponsor must be notified for evaluation of 
whether the patient can continue treatment or not. 


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6.6. 
Dose Modifications 
6.6.1. 
BNT112 (IMP/test product) 
The DLs of BNT112 used in this trial include the 3 DLs for intra-individual patient dose titration 
(
 and 
 µg) and 1 additional dose of 
µg (with
µg of RNA of each antigen) 
which can be used for dose reduction in case of toxicities. A maximum of 2 subsequent dose 
reductions is allowed. Re-escalation to a higher dose level is not allowed. 
For further information about the known and potential risks of BNT112 refer to the latest version 
of the IB.  
6.6.1.1. 
Dose-Limiting Toxicities – Part 1 
For the purpose of intra-patient dose titration, TESAEs, TEAEs ≥Grade 3 and clinically 
significant abnormal lab values at least possibly related to BNT112 cancer vaccine will be 
collected and assessed for DLTs during the first cycle (21 days) of the dose titration part (DLT 
observation period). NCI CTCAE v.5.0 will be used to grade the intensity of TEAEs. At the 
discretion of the investigator, the dose of BNT112 cancer vaccine may be maintained at the 
current DL for one dose, i.e., intra-patient dose titration may be delayed. For these patients, the 
DLT assessment period is extended to 28 days.  
DLT criteria are defined below: 
• Any TEAE of Grade 5 intensity. 
Hematological 
• Grade 3 and 4 febrile neutropenia (i.e., ANC <1.0 × 109 cells/L with a single temperature 
of >38.3°C or a sustained temperature of ≥38°C for more than 1 h). 
• Grade 4 thrombocytopenia (<25.0 × 109 platelets/L) for minimal duration of 7 days. 
• Grade 3 and 4 hemorrhage associated with thrombocytopenia of Grade ≥3. 
• Grade 4 anemia. 
Non-hematological 
• Grade 4 cytokine release syndrome (CRS) according to Lee et al. 201919 (also refer to 
Table 10-5). 
• Grade 3 CRS according to Lee et al. 201919 (also refer to Table 10-5), which has NOT 
improved to Grade 1 or resolved within 48 h. 
• Any Grade ≥3 non-hematological TEAE at least possibly related which occurs during the 
first BNT112 cancer vaccine treatment cycle excluding: 
− Grade 3 CRS according to Lee et al. 201919  (refer to Table 10-5) which has improved 
to Grade 1 or resolved within 48 h. 
− Grade 3 fever (>40.0°C for ≤24 h). 
− Grade 3 hypotension (resolving within 24 h). 
− Related Grade 3 hypertension resolving within 24 h and considered as not clinically 
significant by the SRC. 
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− Grade 3 infusion-related reactions that resolve to Grade ≤1 within 24 h. 
− Non-hematological laboratory abnormalities that have no clinical consequences and 
resolve to Grade ≤2 within 14 days (this also includes electrolyte abnormalities that 
respond to medical intervention). 
− Grade 3 diarrhea that responds to optimal antidiarrheal treatment within 3 days. 
− Grade 3 vomiting that responds to optimal antiemetic treatment within 3 days. 
− Grade 3 nausea that responds to optimal antiemetic treatment within 7 days. 
− Grade 3 fatigue/asthenia when fatigue/asthenia was present at baseline or that lasts for 
<14 days after the last administration of BNT112 cancer vaccine. 
− Grade 3 irTEAEs that improve to Grade ≤1 in <7 days by appropriate care or with 
corticosteroids. 
− Any related Grade 3 AE resolving within 24 h and considered as not clinically 
significant by the SRC. 
All patients will be closely monitored for TEAEs during the DLT assessment period of Part 1.  
TEAEs fulfilling the DLT criteria must be reported to the sponsor within 24 h as described in 
Section 10.3.3.  
6.6.1.2. 
Handling of TEAEs 
Administration of BNT112 may be delayed for up to 21 days at the discretion of the investigator 
in order to adequately manage TEAEs. 
TEAEs that fulfill the DLT criteria both within and outside the DLT period should be handled as 
shown in Figure 6-2. 
Grade 4 TEAEs fulfilling DLT criteria will always lead to BNT112 cancer vaccine 
discontinuation. 
First occurrence of a TEAE of CTCAE Grade 3 fulfilling the DLT criteria: 
• Investigator must contact the sponsor’s medical monitor (MM) for thorough discussion in 
order to decide whether the patient should be withdrawn from BNT112 treatment or the 
next BNT112 dosing should be delayed.  
• Administration of BNT112 can be delayed for up to 21 days (i.e., 1 cycle) unless 
otherwise approved by the sponsor’s MM. If the intensity resolves to Grade ≤1 or 
baseline within this period, re-treatment may be considered under the following 
condition:  
− Sponsor and investigator will discuss any safety concerns in order to decide whether 
the next dose of BNT112 should be administered at the same DL or 1 DL below the 
current dose (i.e., 1 DL below the level of DLT occurrence: DL-1). In case investigator 
and sponsor disagree, the SRC must be consulted. 
Second occurrence in the same patient of an identical TEAE of CTCAE Grade 3 after re-
exposure to BNT112: 
• If re-treatment leads to an identical TEAE with same intensity, the next administration of 
BNT112 can be delayed for up to 21 days unless otherwise approved by the sponsor’s 


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MM. If the intensity of the TEAE resolves to Grade ≤1 or baseline within this period, re-
treatment may be considered under the following conditions: 
− Next dose of BNT112 should be administered 1 DL below the level of TEAE 
recurrence (DL-1 or DL-2). 
Third occurrence of an identical TEAE of Grade ≥2 after re-exposure to BNT112: 
• If re-treatment at a lower dose leads to a third identical TEAE with intensity Grade ≥2, 
the patient must permanently discontinue BNT112 treatment. No dose delay is allowed.  
See Figure 6-2 for a decision tree for possible dose reductions and dosing delays required for 
TEAEs that fulfill the DLT criteria both within the DLT period and outside the DLT period.  
 
Figure 6-2: 
Handling of TEAEs fulfilling the DLT criteria 
 
Abbreviations and Footnotes: 
AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; G = grade, grading according to 
CTCAE v5.0; TEAE = treatment-emergent adverse event. 
* 
Dose delay: Next dose of BNT112 can be delayed by a maximum of 21 days unless approved otherwise by the 
sponsor’s MM. 
# 
No delay for recovery from CTCAE Grade ≥2 allowed. 
## Unless baseline CTCAE Grade was ≥2 and TEAE has resolved to baseline grade. 
 
Please note: 
• Re-escalation of BNT112 dose is not allowed for patients that previously have been dose-
reduced based on investigator’s, sponsor’s, and SRC’s decision. 
• BNT112 must be permanently discontinued if the patient experiences an AE fulfilling the 
DLT criteria during any period of the trial even if outside the DLT period that fails to 


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resolve to Grade ≤1 within 21 days after the planned dosing date unless otherwise 
approved by the sponsor’s MM. 
• BNT112 must be permanently discontinued if > 2 dose reductions are required. 
• BNT112 must be permanently discontinued in case of a dose delay of > 21 days due to 
toxicity possibly related to BNT112 unless otherwise approved by the sponsor MM. 
6.6.2. 
Cemiplimab (IMP) 
No dose reduction of cemiplimab is recommended. 
Cemiplimab should be withheld in the following conditions: 
• Grade 2 pneumonitis 
• Grades 2 or 3 colitis 
• Hepatitis (aspartate transaminase [AST] or alanine [ALT]) increased >3 and ≤10 times 
the upper limit of normal [ULN], or total bilirubin increased ≤3 times the upper limit of 
normal) 
• Grades 2–4 endocrinopathies (withhold if clinically necessary) 
• Other immune-mediated Grade 3 adverse reactions involving a major organ 
Cemiplimab should be permanently discontinued in the following conditions: 
• Grades 3 or 4 pneumonitis 
• Grade 4 colitis 
• Hepatitis (AST or ALT increased >10 times the ULN or total bilirubin increased >3 times 
the ULN) 
• Grades 3 or 4 infusion-related reactions 
• Recurrent or persistent immune-mediated adverse reactions (persistent for ≥ 12 weeks 
after the last dose or requiring prednisone ≥ 10 mg/day or the equivalent for ≥12 weeks 
after last cemiplimab dose) 
Additional and more detailed information about when cemiplimab should be withheld or 
discontinued in order to manage TEAEs are described in the relevant country label or SmPC. 
For further information about the known and potential risks of cemiplimab refer to the latest 
version of the IB.  
6.6.3. 
ADT (e.g., Goserelin acetate; NIMP) 
No dose modification is allowed for goserelin acetate. Patients receiving goserelin acetate will 
remain on the assigned dose of goserelin acetate (10.8 mg Q12W) throughout the course of the 
trial or until 1 of the predefined discontinuation-of-treatment criteria defined in has been met (see 
Section 7). In case another ADT is given instead of goserelin acetate, respective prescribing 
information valid in a given country should be followed for dose modifications or until 1 of the 
predefined discontinuation-of-treatment criteria defined has been met (see Section 7). 


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6.7. 
Treatment After the End of the Trial 
No trial treatment is currently envisioned beyond the end of the trial treatment period as defined 
in the SoA for the respective treatment arms (i.e., Month 12). 
7. 
Discontinuation of Trial Treatment and Patient 
Discontinuation/Withdrawal 
7.1. 
Discontinuation of Trial Treatment 
In rare instances, it may be necessary for a patient to permanently discontinue (definitive 
discontinuation) trial treatment.  
Patients will be withdrawn from the trial treatment if any of the following applies: 
• Patient withdraws his consent to trial participation.  
• Unacceptable toxicity. 
• Evidence of clinical disease progression as defined by PCWG3 criteria29 (Part 1 and Part 2 
Arms 1A and 1B). Part 2 Arm 1B: following progression after BNT112 monotherapy, 
patients will have the option to be treated with cemiplimab
mg IV Q3W. 
Note: If the investigator considers radiographic changes secondary to drug-induced 
inflammation and not due to tumor progression, the investigator may postpone a 
diagnosis of PD until the next radiographic evaluation in the trial. 
• Part 2 Arms 2 and 3: the planned surgery for prostate cancer can be performed at any 
time during the 6 months’ treatment at the discretion of the investigator. 
• Development of any intercurrent illness or situation which may, in the judgment of the 
investigator, affect assessments of clinical status and trial endpoints to a relevant degree. 
• Development of a second malignancy that requires a different treatment. 
• Substantial non-compliance with trial procedures. 
• Use of illicit drugs, prohibited concomitant treatment, or other substances that may, in the 
opinion of the investigator, have a reasonable chance of contributing to toxicity or 
otherwise confound the results. 
• Patient is lost to follow-up. 
If either BNT112 or cemiplimab needs to be discontinued, treatment with either cemiplimab or 
BNT112 can continue upon investigator’s and sponsor’s agreement. As ADT has been selected 
as the backbone therapy for patients with LPC in this trial, if treatment with ADT (e.g., goserelin 
acetate) needs to be discontinued, cemiplimab and/or BNT112 also need(s) to be discontinued to 
minimize the risk of the delay of the radical prostatectomy. 
See the SoA for data to be collected at the time of treatment discontinuation and follow-up and 
for any further evaluations that need to be completed. 
CCI


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7.2. 
Patient Discontinuation/Withdrawal from the Trial 
A patient 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, behavioral, compliance, or administrative 
reasons. This is expected to be uncommon. 
At the time of discontinuing from the trial, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA. See SoA for data to be collected at the time of trial 
discontinuation and follow-up and for any further evaluations that need to be completed. 
If the patient withdraws consent for disclosure of future information, the sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
If a patient withdraws from the trial, he may request destruction of any samples taken and not 
tested, and the investigator must document this in the site trial records. 
7.3. 
Lost to Follow-up 
A patient will be considered lost to follow-up if he repeatedly fails to return for scheduled visits 
and is unable to be contacted by the trial center. 
The following actions must be taken if a patient fails to return to the clinic for a required trial 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
trial. 
• Before a patient is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the patient (where possible, 3 telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, he will be considered to have withdrawn 
from the trial.  
Discontinuation of specific sites or of the trial as a whole are described in Section 10.1.9. 
8. 
Trial Assessments and Procedures 
Trial procedures and their timing are summarized in the SoA. Protocol waivers or exemptions 
are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the patient should continue or discontinue trial treatment. 
Adherence to the trial design requirements, including those specified in the SoA, is essential and 
required for trial conduct. 
All screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
patients screened and to confirm eligibility or record reasons for screening failure, as applicable. 


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Procedures conducted as part of the patient’s routine clinical management (e.g., blood count) and 
obtained before signing of the ICF may be utilized for screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA. 
8.1. 
Efficacy Assessments 
8.1.1. 
Clinical Monitoring of Tumor Lesions 
8.1.1.1. 
Prostate Cancer Imaging 
The efficacy in mCRPC (Part 1 and Part 2 Arms 1A and 1B) will be assessed by radiographic 
progression as defined in PCWG3 guideline and iRECIST guideline and/or unequivocal clinical 
progression. The efficacy in neoadjuvant LPC (Part 2 Arms 2 and 3) will be assessed by tumor 
measurement using mpMRI or MRI. The same imaging modality should be used at screening 
and at all subsequent assessments.  
If the investigator considers radiographic changes secondary to drug-induced inflammation and 
not due to tumor progression, the investigator may postpone a diagnosis of PD until the next 
radiographic evaluation in the trial.  
Additional CT-scans or MRI-scans should be performed at the investigator’s discretion to 
confirm response or potential progression of the disease (e.g., patients with confirmed PSA 
doubling during trial treatment). 
Same imaging modalities should be kept throughout the trial to optimize the reproducibility of 
the assessment and preserve the accuracy of the assessment of response or progression. An 
Imaging Acquisition Guideline will be provided for guidance. All records and films of 
responding patients (CR, PR, and stable disease [SD]) must be available for eventual extramural 
review of the tumor. 
mCRPC patients (Part 1 and Part 2 Arms 1A and 1B) 
Bone scintigraphy (bone scans) and CT/MRI chest, abdomen, and pelvis should be performed at 
the following time points:  
• During the screening period (within 28 days before C1D1 [baseline]) 
• At C3D15 (± 7 days)  
• Then every 8 weeks (±7 days) for 24 weeks, i.e., between C6D1 and C8D15 
• And every 3 months (±7 days) thereafter, i.e., from C11D15 until disease progression is 
assessed by the investigator or the start of new anti-cancer therapy or withdrawal of 
consent, or death, whichever occurs first 
• At EoT visit (only if clinically indicated); not required if previous imaging was 
performed within ≤9 weeks before the EoT visit 
Patients in Arm 1B who move to treatment with cemiplimab monotherapy following progression 
after BNT112 monotherapy, should have radiographic assessments performed every 3 months 
(±7 days) thereafter, until disease progression is assessed by the investigator or the start of new 
anti-cancer therapy or withdrawal of consent, or death, whichever occurs first. 


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LPC patients (Part 2 Arms 2 and 3) 
Tumor measurement using mpMRI or MRI will be used consistently for assessment. The same 
imaging modality should be used at screening and at all subsequent assessments. Tumor 
measurements should be performed at the following time points:  
• During the screening period (within 28 days before C1D1 [baseline]) 
• Prior to surgery (i.e., at the end of C8/EoT visit). 
For guidance on the mpMRI, see the Imaging Acquisition Guideline. 
8.1.1.2. 
Tumor Response Assessment 
Part 1 and Part 2 Arms 1A and 1B 
In patients with mCRPC, response to treatment with BNT112 as monotherapy or in combination 
with cemiplimab will be assessed for the following outcome measures based on post-baseline 
radiographic images as defined above. 
• ORR (CR or PR) using PCWG3 criteria29 and iRECIST criteria30 
• DoR, using PCWG3 criteria29 
• PFS using PCWG3 criteria29 and iRECIST criteria30 
• Criteria for disease response assessment are provided in Appendix 9. 
The PCWG3 criteria29 will be used for endpoint response evaluation as well as follow-up tumor 
assessment and will be done by a local radiologist.  
The iRECIST criteria30 will be used for exploratory endpoint response evaluation and will be 
done retrospectively centrally by an imaging laboratory. 
Patients in Arm 1B will be given the option to be treated with cemiplimab monotherapy 
following progression on BNT112 monotherapy treatment and will be assessed for the same 
outcome measures as listed above, where the last measurement prior to start of cemiplimab 
treatment will serve as baseline measurement and the time-to-event endpoints (DoR, and PFS) 
will start from first dose of cemiplimab treatment. In particular, the last radiographic tumor 
assessment prior to cemiplimab treatment will re-define target and non-target lesions as basis for 
tumor response assessment on cemiplimab treatment. Additionally, PFS2 will be evaluated based 
on initial treatment. 
Part 2 Arms 2 and 3 
In patients with LPC, response to neoadjuvant treatment with BNT112 plus cemiplimab (Part 2 
Arm 2) and BNT112 alone (Part 2 Arm 3) will be assessed for the following outcome measure 
based on post-baseline radiographic images as defined above: 
• mpMRI or MRI tumor assessment post-treatment compared to baseline. 
The tumor assessment will be used for endpoint response evaluation and will be done by a local 
radiologist; in addition, based on the sponsor’s decision, a central read by an imaging laboratory 
can be added. The same imaging modality should be used at screening and at all subsequent 
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8.1.2. 
Survival Status and Biochemical Recurrence 
Survival status will be assessed at month 6 and month 12 (±14 days), beginning from the day of 
last IMP dose and continues until the patient dies or withdraws from the trial. Patients may be 
contacted by telephone, E-Mail, or visit. Survival status may be requested more frequently 
around the time of a database lock. Patients or whose designated family members are not 
available for this assessment should be entered as “lost to follow-up”. 
Biochemical recurrence after radical prostatectomy based on post-treatment PSA levels at 
month 12 will be assessed for patients in Part 2 Arms 2 and 3. 
8.2. 
Safety Assessments 
8.2.1. 
Physical Examination 
Physical examinations will be performed (by inspection, palpation, and auscultation) by a 
physician at the trial center at the time points specified in Section 1.3 (Part 1 and Part 2 Arms 1A 
and 1B), Section 1.4 (Part 2 Arms 2 and 3), and Section 1.5 (Part 2 Arm 1B [switch-over 
patients]). Comprehensive physical examinations will be performed at screening. During the 
treatment the investigators should make an overall health judgment and make only in-depth 
examinations if clinically indicated.  
Depending on timing (before or after signing the ICF for trial participation), the clinically 
significant findings of the physical examination have to be recorded as medical/surgical history 
or as AEs (see Section 10.3.3). 
Comprehensive physical examination 
At a minimum, the following aspects/regions need to be assessed: 
• General appearance 
• Skin  
• Eyes  
• Ears, nose, throat  
• Head and neck 
• Lungs 
• Heart 
• Abdomen (pain, tenderness, peristaltic, ascites, organomegaly) 
• Lymph nodes 
• Musculoskeletal system (including extremities and spine) 
• Neurologic findings 
The following will be examined by specialists, if applicable: 
• Genito-urinary system 
• Anus/Rectum 


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If a patient states any symptoms that might be related to prostatitis or other prostate-related 
condition, further investigations like digital rectal examination, ultrasound should be initiated. 
Abbreviated physical examination 
The abbreviated physical examination includes an overall health judgment and brief interim 
history (change of symptoms). In-depth physical examinations are required if obvious 
pathological signs are visible or in the case the patient states any signs or symptoms.  
For details regarding the measurement of body weight/height and vital signs (blood pressure, 
pulse, body temperature), please refer to Sections 8.2.2 and 8.2.5. 
8.2.2. 
Clinical Laboratory Tests 
Details on safety laboratory tests are provided in Table 10-1. 
8.2.3. 
Vital Signs 
Vital signs (blood pressure, pulse rate, body temperature) will be measured by a member of the 
investigator’s team at the time points specified in Section 1.3 (Part 1 and Part 2 Arms 1A and 
1B), Section 1.4 (Part 2 Arms 2 and 3), and Section 1.5 (Part 2 Arm 1B [switch-over patients]).  
• Patient’s systolic/diastolic blood pressure is measured in mmHg and pulse rate in bpm in 
sitting or supine position after at least 5 minutes rest.  
• Body temperature will be measured in °C. 
The same method of measurement should be used for the patient during the course of the trial. 
8.2.4. 
Electrocardiogram 
A single standard 12-lead electrocardiogram (ECG) will be recorded at the time points specified 
in Section 1.3 (Part 1 and Part 2 Arms 1A and 1B), Section 1.4 (Part 2 Arms 2 and 3), and 
Section 1.5 (Part 2 Arm 1B [switch-over patients]). 
ECG will be evaluated by the investigator and will be documented in the eCRF. 
8.2.5. 
Body Weight and Height 
Patient’s body weight (in kg) and height (in cm) will be measured by a member of the 
investigator’s team at the time points specified in Section 1.3 (Part 1 and Part 2 Arms 1A and 
1B) and Section 1.4 (Part 2 Arms 2 and 3). 
8.2.6. 
ECOG PS 
Patient’s ability to manage activities of daily living will be appraised utilizing the performance 
status scale developed by the Eastern Cooperative Oncology Group published in 1982 (see 
Appendix 7).  
The patient’s ECOG PS will be estimated by a physician of the investigator’s team at the time 
points specified in Section 1.3 (Part 1 and Part 2 Arms 1A and 1B), Section 1.4 (Part 2 Arms 2 
and 3), and Section 1.5 (Part 2 Arm 1B [switch-over patients]). An ECOG PS score of 0 or 1 is 
required for trial inclusion (see Section 10.6). 
Planned time points for all safety assessments are provided in the SoA. 


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8.3. 
Other Assessments 
8.3.1. 
Demographic Data 
At screening, the following demographic data will be recorded for all patients enrolled in this 
trial: age, gender (must be male), and ethnic group. The patients of all races/ethnicity can 
participate in the trial provided that they meet all eligibility criteria. 
8.3.2. 
Medical History 
At screening, the following relevant information on patient’s medical history will be recorded: 
• Documentation of prostate cancer history: 
− Month/year of initial diagnosis  
− Prior cancer treatment and previous diagnostic and therapeutic procedures 
− Tumor stage (TNM system), tumor grade (Gleason score) and risk group according to 
European Association of Urology Guidelines on Prostate Cancer  
− PSA at diagnosis 
− Documentation for confirmation of inclusion diagnosis: histopathology report, 
radiology report of bone scan, CT/MRI performed <2 months before screening (see 
Section 5.1: inclusion criteria) 
• Documentation of relevant concomitant diseases/disorders and surgeries (start/stop date 
or ongoing) 
• Tetanus vaccination status 
8.3.3. 
Surgery-related Assessments 
In this trial, newly diagnosed LPC patients randomized to Arms 2 and 3 will be given 
neoadjuvant treatment with BNT112 up to Cycle 8 (week 21) before surgery (radical 
prostatectomy).  
The surgery is scheduled after the EoT visit and is not part of this trial. However, the following 
trial-related procedures/assessments are required and will be documented in the eCRF:  
Pre-surgery:  
• Prostate cancer imaging  
During surgery:  
• Date of surgery  
• Fresh tumor tissue sample(s) taken intraoperatively for tumor marker analysis; if no fresh 
tissue sample is available, a formalin-fixed, paraffin-embedded (FFPE) sample of the 
tumor will be obtained 
8.4. 
AEs and SAEs 
AEs will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or the 
patient's legally authorized representative). 


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The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the trial treatment or trial procedures, or that 
caused the patient to discontinue the trial treatment (see Section 7). 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs will be collected from signing of the ICF until the safety FU visit at the time points 
specified in the SoA (Section 1.3 [Part 1 and Part 2 Arms 1A and 1B], Section 1.4 [Part 2 
Arms 2 and 3], and Section 1.5 [Part 2 Arm 1B, switch-over patients]). 
All SAEs will be collected from signing of the ICF until the safety FU visit at the time points 
specified in the SoA (Section 1.3 [Part 1 and Part 2 Arms 1A and 1B], Section 1.4 [Part 2 
Arms 2 and 3], and Section 1.5 [Part 2 Arm 1B, switch-over patients]). 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 h, as indicated in Section 10.3.4. The investigator will submit 
any updated SAE data to the sponsor within 24 h of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the trial 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a patient has been discharged from the trial, and he/she considers the event to be reasonably 
related to the trial treatment or trial participation, the investigator must promptly notify the 
sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each patient at 
subsequent visits/contacts. All AEs/SAEs will be followed until resolution, stabilization, the 
event is otherwise explained, or the patient is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Section 10.3.3. 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of patients and the safety of a trial 
treatment 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 treatment under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), 


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and investigators. The execution of expedited reporting to the different entities may be delegated 
as detailed in the trial-specific Safety Management Plan.  
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. 
For the IMPs, sponsor or delegate will take care of the SUSAR reporting to the regulatory 
authority, the IRB/IEC and the other investigators as required by national law and applicable 
guidelines. 
All AEs suspected to be related to the NIMP should be sent by the investigator to the national 
competent authority in the country where it occurred (according to the national legislation) or to 
the marketing authorization holder of the NIMP, but not to both to avoid duplicate submissions 
(ENTR/CT-3, GVP Module VI EMA/873138/2011 Rev 2). 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the respective IB (BNT112 or cemiplimab) and will notify the IRB/IEC, if 
appropriate according to local requirements. 
8.4.5. 
Pregnancy 
Only males will be included. After signing the ICF, patients who are sexually active with a 
woman of childbearing potential must agree to use a condom with spermicidal 
foam/gel/film/cream/suppository. Additionally, patients or their partners are required to use at 
least one form of highly effective contraception (please refer to Table 10-3). This must be 
adhered to for the duration of trial treatment and for 90 days after receiving the last dose of 
BNT112 OR for 6 months after the last dose of cemiplimab. 
Details of all pregnancies in female partners of male patients will be collected after the start of 
trial treatment and until 90 days after the last dose of BNT112 and 6 months after the last dose of 
cemiplimab. 
If a pregnancy of a female partner is reported, the investigator should inform the sponsor within 
24 h of learning of the pregnancy and should follow the procedures outlined in Section 10.4. 
Patients should not donate sperm during the trial starting after signing the ICF and for 90 days 
after receiving the last dose of BNT112 OR for 6 months after receiving the last dose of 
cemiplimab. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.  
8.4.6. 
Death  
Any death that occurs within the observation period will be reported as an SAE. Exemptions to 
the SAE definition as defined in Section 10.3.3 do also apply for fatal cases. A copy of an 
autopsy report should be submitted if available. Date and cause of death will be recorded. 
In case of a fatal event, the event term should not be “death” but the underlying event which led 
to death (death = outcome). If there is more than 1 AE in a fatal case, only for the AE leading to 


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death the outcome “fatal” should be selected. If the cause of death is unknown and cannot be 
ascertained at the time of reporting, “unexplained death” should be documented as event term. 
In addition to reporting as SAE, the death page of the eCRF needs to be completed. 
8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
The progression of underlying disease (e.g., new metastases, increase of PSA value) during trial 
participation is not considered as AE. The following disease-related event (DRE) is common in 
patients with prostate cancer and can be medically relevant and/or serious/life-threatening: 
• The progression of prostate cancer (e.g., new metastases, PSA increase) 
Because disease progression is common for patients with cancer, it will not be reported 
according to the standard process for expedited reporting of SAEs even though the event may 
meet the definition of a SAE. These events will be recorded on the corresponding eCRF page in 
the patient’s eCRF. This DRE will be monitored by an SRC on a routine basis. See Section 9.6. 
Note: However, specific symptoms at time of progression that are considered that may be caused 
by other reasons, and fatal cases where other reasons rather than the PD may not be discarded, 
will have to be documented as AEs and reported as SAEs if applicable. 
8.5. 
Treatment of Overdose 
For this trial, any dose of trial treatment greater than 110% of the intended dose of either 
BNT112 or cemiplimab specified in the protocol will be considered an overdose. 
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should: 
• Contact the MM immediately. 
• Closely monitor the patient for any AE/SAE and laboratory abnormalities (at least 
21 days). 
• Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the MM based on the clinical evaluation of the patient. 
8.6. 
Pharmacokinetics 
Pharmacokinetic parameters are not evaluated in this trial. 
8.7. 
Pharmacodynamics 
Potential pharmacodynamic parameters are evaluated in this trial and described in the next 
Section 8.8. 


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8.8. 
Biomarkers 
Blood samples and tumor samples for biomarker analysis will be collected from patients with 
mCRPC (Part 1 and Part 2 Arms 1A and 1B) and LPC (Part 2 Arms 2 and 3) at the time points 
shown in the SoA (Section 1.3, Section 1.4, and Section 1.5 respectively). 
The selected biomarkers will be used as follows:  
• For tracking the progression of prostate cancer (diagnostic markers, e.g., PSA); therefore, 
patient’s blood samples will be tested for levels of PSA. 
• To monitor the safety of investigational treatment (e.g., cytokines).  
• To investigate immuno-pharmacodynamics of BNT112 to evaluate the MoA and identify 
the optimal dosage regimen for guiding treatment strategies (MoA/Pharmacodynamics 
biomarkers). As an exploratory endpoint, T cell responses against each of the vaccine 
antigens in patient’s blood samples will be analyzed.  
• Additionally, potential pharmacodynamic and predictive biomarkers that may identify 
patients that can benefit from therapy may be addressed: 
− Blood and tumor samples will be collected in order to perform profiling of T cell 
receptors (TCR profiling) in the periphery and tumor as potential predictive marker as 
well as surrogate for pharmacodynamics. 
− Tumor samples may also be investigated with regards to intratumoral changes of 
infiltrating immune cells by immunohistochemistry. 
− Furthermore, fresh tumor samples (non-FFPE material) will be collected in order to 
investigate anti-tumor specific activity within the tumor by functional T cell tests (such 
as ELISpot) and phenotypic characterization of tumor-antigen-specific T cells. For the 
latter, the patient’s blood has to be characterized with regards to the respective human 
leukocyte antigen (HLA) type. 
− Furthermore, i) the mRNA expression of vaccine antigens in the tumor may be 
investigated, as well as ii) specific mutations in tumor DNA in order to evaluate tumor 
mutational burden, and iii) the identification of RNA expression pattern of immune-
relevant genes. For these analyses, patient’s tumor samples will be collected.  
The biomarker parameters will be analyzed by different laboratories (central laboratory and 
specialty laboratories). Detailed information about the handling, labeling, and shipment of blood 
samples for biomarker analysis will be provided in a separate document (i.e., Laboratory 
Manual). 
Optional samples for biomarker research that should be collected from patients in the trial where 
possible are the following: 
• Blood and tumor tissue (analyses as described above will be performed with these 
additional samples) 
• On-treatment tumor samples from biopsies or tumor resections done as part of the clinical 
management of the patient (e.g., palliative surgery) will optionally be provided for 
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In addition, samples will be stored and analysis may be performed on biomarker variants thought 
to play a role in the MoA of BNT112 including, but not limited to, blood and tumor tissue 
biomarkers to evaluate their association with observed clinical responses to BNT112 alone, or in 
combination with cemiplimab and/or ADT (e.g., goserelin acetate). 
Other samples may be used for research to develop methods, assays, prognostics and/or 
companion diagnostics related BNT112 alone, or in combination with cemiplimab and/or ADT 
(e.g., goserelin acetate) in prostate cancer. 
Biomarker samples may be stored up to 5 years after the trial ends. Biomarker analyses may be 
deferred or not performed, if during or at the end of the trial, is becomes clear that the analysis 
will not have sufficient scientific value for biomarker evaluation, or if there are not enough 
samples to allow adequate evaluation. In the event the trial is terminated early or shows poor 
clinical efficacy, completion of biomarker assessments is based on justification and intended 
utility of the data. 
The results of this additional research may not be presented in the Clinical Study Report (CSR). 
These results may be presented outside of the CSR. 
8.9. 
Immunogenicity Assessments 
Immunogenicity will be assessed using relevant biomarkers (refer to details in Section 8.8). 
9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
For each Part 2 Arm 1A and 1B the null hypothesis that the true response rate is 5% will be 
tested against a one-sided alternative (i.e., H0: ORR=5% vs H1: ORR>5%). There will be no 
formal comparison between treatment arms. No further statistical hypothesis is under test. 
9.2. 
Sample Size Determination 
The sample size for Part 1 is driven by the 3+3+3 trial design and will range from 3 to 9 DLT 
evaluable patients depending on the number of DLTs which may occur. The main objective for 
the Part 2 is to perform exploratory biomarker analyses in the LPC setting and to preliminary 
assess the efficacy in terms of response in the mCRPC setting.  
Simon's two-stage design (Simon, 198931) based on the Minimax approach will be used for 
Part 2 Arm 1A and 1B separately. The null hypothesis that the true response rate is 5% will be 
tested against a one-sided alternative. In the first stage, 20 evaluable patients will be treated. 
Enrollment will continue following sponsor decision (upon recommendation from the SRC 
following review) and 13 evaluable patients may be treated for a total of 33 evaluable patients. If 
there is one or fewer responses in the first 20 evaluable patients, the enrollment for that arm may 
be stopped. The null hypothesis will be rejected if five or more responses are observed in 
33 evaluable patients. This design yields a type I error rate of 2.5% and power of 80% when the 
true response rate is 20%. 
A patient will be considered as evaluable if included in the primary analysis set (mITT set, see 
Section 9.3) which is defined as all patients who are randomized to the IMP and have a baseline 


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and at least one post-baseline (i.e., one on-treatment or post-treatment) tumor assessment 
(clinical or imaging assessment). 
No formal sample size calculation is performed for the LPC setting in Part 2 (Arms 2 and 3) due 
to its exploratory nature. However, 20 patients are planned to be enrolled into Arm 2 and Arm 3. 
Based on this sample size (N=20) the one-sided 95% CI of binary endpoints will have a width of 
up to +/-0.19 in each group depending on the observed effect size. 
9.3. 
Analyses Sets 
The following analysis sets are defined: 
 
Population 
Description 
Screened  
The screened analysis set is defined as all patients who sign the 
ICF. 
Intent-to-Treat (ITT) 
The ITT set is defined as all patients who are randomized to the 
IMP. 
Modified Intent-to-Treat 
(mITT) 
The mITT set is defined as all patients who are randomized to the 
IMP and have a baseline and at least one post-baseline (i.e., one 
on-treatment or post-treatment) tumor assessment (clinical or 
imaging assessment). 
DLT Evaluation 
The DLT evaluation set includes all patients from the safety set 
who either have completed the DLT evaluation period and meet 
the minimum exposure criterion or have experienced a DLT 
during C1.  
Patients who do not experience any DLTs during C1 are 
considered to be evaluable if they have been observed for 
minimum of 21 days following the first dose and are considered 
to have sufficient safety data to conclude that a DLT did not 
occur. A patient is considered to have met the minimum 
exposure criterion if the RDI of BNT112 in C1 is at least 90%.  
Safety 
The safety set is defined as all patients who received IMP (i.e., at 
least 1 dose of BNT112 and/or cemiplimab). 
Pharmacodynamic 
The Pharmacodynamic analysis set is defined as all patients with 
baseline and at least 1 on-treatment/post-treatment follow-up 
pharmacodynamic assessment. 
 
The DLT evaluation set will be used for the evaluation of DLTs in order to assess the REDR. 
The safety set will be used for all other safety analyses, while the mITT set will be used for 
efficacy analyses. Arm 1b will be additionally analyzed for patients who received cemiplimab 
(i.e., at least 1 dose of cemiplimab) after progression to BNT112 monotherapy.  


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All safety analyses will be based on the treatment actually taken by the patient (“as treated”). All 
other analyses will be based on the treatment the patient was assigned/randomized to (“as 
randomized”), unless stated otherwise. 
9.4. 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to database snapshot for the main 
analysis 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 secondary endpoints. 
9.4.1. 
General Considerations 
Statistical analyses will be performed by the sponsor or a designated CRO. All statistical 
analyses will be carried out using SAS® Version 9.4 or higher, and/or other statistical software as 
required. 
In general, the statistical analysis will be performed by trial part (i.e., Part 1 and Part 2, 
respectively) and by treatment group in Part 2 (i.e., Arm 1A, Arm 1B, Arm 2 and Arm 3).  
Continuous variables will be summarized by treatment group using the following descriptive 
statistics: n, mean, standard deviation, median, minimum, and maximum. 
Categorical variables will be summarized by treatment group presenting absolute and relative 
frequencies (n and %) of patients in each category.  
Time-to-event-endpoints (DoR, PFS, and OS) will be analyzed using Kaplan-Meier methodology 
and censored in accordance with the FDA Guidance: “Clinical Trial Endpoints for the Approval 
of Cancer Drugs and Biologics.” Censoring rules will be defined in the SAP. Number of patients 
with events, censored and under risk as well as the median, first and third quartile of time-to-
event (including 95% confidence limits according to Brookmeyer and Crowley) will be 
presented. Survival rates including 95% confidence interval based on Greenwood's formula will 
be displayed after 3 months, after 6 months and after 12 months. 
Baseline is defined as last available value prior to randomization/first dose of IMP. 
In the following sections basic statistical analyses will be described. Further details of statistical 
analyses will be provided in the SAP. Additional statistical analyses may be added in the SAP. 
9.4.2. 
Primary Endpoints 
DLTs and AEs 
The primary endpoint is the occurrence of DLTs and AEs reported by relationship, grade, and 
seriousness according to NCI CTCAE v5.0. The number and percentage of patients with any 
DLT and/or AE will be presented for patients enrolled into Part 1 and for each arm in Part 2. 
Moreover, a patient listing will be provided with all relevant dose exposure data of all patients 
enrolled into Part 1 and for each arm in Part 2 and a listing of all recorded DLTs and/or AEs will 
be presented including the reported term and Medical Dictionary for Regulatory Activities 
(MedDRA®) PT and SOC term, its time of onset, relationship, NCI CTCAE grade, and 
seriousness including dose exposure data (e.g., BNT112 DL). 


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Objective Response Rate 
For Arm 1A and 1B in Part 2, ORR is defined as primary efficacy endpoint. 
The ORR is defined as the number of patients with CR or PR as best objective response divided 
by the number of patients in the analysis set. Patients not meeting the criteria for CR or PR, 
including those without any post-baseline tumor assessments, will be considered as non-
responders. The ORR will be summarized with absolute and relative frequencies along with two-
sided 95% Clopper-Pearson confidence intervals by treatment group/cohort.  
The primary analysis will be performed using the mITT set. 
For Part 1, ORR is defined as secondary endpoint ORR and will be analyzed descriptively. 
9.4.3. 
Secondary Endpoints 
PSA Decline  
PSA decline of 0 to 25%, >25% to 50%, and >50% compared to baseline will be summarized 
with absolute and relative frequencies (n and %) of patients in each category. PSA decline of 
≥50% (according to the PCWG3) will be summarized with absolute and relative frequencies (n 
and %) of patients in each category. 
PSA Doubling Time 
The number and percentage of patients per PSADT under-treatment compared to baseline. 
Tumor Response  
For Arm 2 and 3 in Part 2, tumor response is defined as secondary efficacy endpoint.  
Secondary efficacy analyses will be performed using the mITT set. 
9.4.4. 
Exploratory Endpoints 
Exploratory Immunogenicity Analyses 
Exploratory immunogenicity analyses will be further defined in the SAP. 
BNT112 antigen-specific T cells 
Occurrence of de novo induction or increase of BNT112 antigen-specific T cells in peripheral 
blood under treatment on C3D15 and/or C8D15, EoT, or safety follow-up compared to baseline 
will be summarized with absolute and relative frequencies (n and %) of patients in each category. 
Exploratory Efficacy Analyses 
Exploratory efficacy analyses will be performed using the mITT set. 
Exploratory efficacy endpoints comprise ORR (in the mCRPC arms and only per iRECIST), 
DoR, PFS, and OS. Tumor assessments will be performed using PCWG3 and iRECIST. DoR 
and PFS will be analyzed separately for PCWG3 and iRECIST.  
Exploratory efficacy analyses will also be performed on patients in Arm 1B who are treated with 
cemiplimab monotherapy following progression after BNT112 monotherapy. These exploratory 
analyses will comprise ORR, DoR, PFS (per PCWG3 and iRECIST) on cemiplimab 
monotherapy based on last tumor assessment prior to start of cemiplimab treatment and OS. 
PFS2 will be analyzed as well. Further details will be described in the SAP. 


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Duration of Response  
The DoR is defined as the time from the date of first radiographic documented OR to the date of 
first disease progression. Only patients who experience a confirmed CR or PR will be analyzed 
for DoR. DoR will be analyzed using the Kaplan-Meier method. Patients alive and without 
disease progression at data cut-off date or patients lost to follow-up will be censored at the day of 
their last tumor assessment. Additional censoring rules will be defined in the SAP. 
Progression-free Survival  
PFS is defined as the time from the date of first dose of IMP/randomization to the date of first 
disease progression, or death from any cause, whichever occurs first. PFS will be analyzed using 
the Kaplan-Meier method. Patients alive and without disease progression at the data cut-off date 
or patients lost to follow-up will be censored at the day of their last tumor assessment. If no 
baseline or post-baseline tumor assessment is available, the patient will be censored at the date of 
first dose of IMP/randomization. Additional censoring rules will be defined in the SAP.  
Overall Survival 
OS is defined as the time from the date of first dose of IMP/randomization to the date of death 
from any cause. OS will be analyzed using the Kaplan-Meier method. Patients alive or patients 
lost to follow-up at the date of analysis cut-off will be censored at the day of their last date 
known to be alive. Additional censoring rules will be defined in the SAP. 
9.4.5. 
Safety Analyses 
Safety data that will be summarized include exposure, AEs, clinical laboratory assessments, vital 
signs and ECGs. All safety analyses will be based on the safety set and will be summarized by 
treatment group unless otherwise stated. 
Treatment Exposure 
The following dose exposure variables will be derived and analyzed for each compound: 
• Number of cycles 
• Treatment duration (weeks) defined as follows: 
o (Date of last administration - date of first administration + planned duration)/7, 
whereas the Planned Duration (days) is defined as the planned time between two 
consecutive administrations. 
• Cumulative Dose (µg [BNT112] / mg [cemiplimab]) defined as sum of all administered 
doses 
• Dose Intensity (DI) defined as Cumulative Dose/Treatment Duration 
• Relative Dose Intensity (RDI) defined as follows: 
RDI (%) = Actual Dose Intensity 
Planned Dose Intensity  x 100 = DI x TI x 100,  
whereas 
(Actual) Dose Intensity =
(Actual) Cumulative Dose
(Actual) Treatment Duration  


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Planned Dose Intensity =
Planned Cumulative Dose
Planned Treatment Duration   
Dose Index = Total Administered Dose 
Total Planned Dose 
 
Time Index = Planned Treatment Duration 
Actual Treatment Duration  
AEs 
AEs will be coded using the most recent version of MedDRA® coding system to get a SOC and 
PT for each AE and graded for severity using NCI CTCAE v5.0.  
A TEAE is defined as any AE with an onset date on or after the first administration of IMP (if 
the AE was absent before the first administration of IMP) or worsened after the first 
administration of IMP (if the AE was present before the first administration of IMP). AEs with 
an onset date more than 30 days or 90 days, respectively for BNT112 or cemiplimab, after the 
last administration of IMP will be considered as treatment-emergent only if assessed as related to 
the IMP by the investigator. TEAEs will be summarized overall and by treatment arm.  
For Arm 1B, the analysis of AEs will be additionally performed for each IMP separately, i.e. 
TEAEs from first dose of BNT112 until last dose of BNT112 +30 days and TEAEs from first 
dose of cemiplimab until last dose of cemiplimab +90 days, respectively.  
The number and percentage of patients reporting at least one AE will be summarized by PT 
nested within SOC for each of the following AE types:  
• Any AE 
• Related AE 
• Grade ≥3 AE 
• Related Grade≥3 AE 
• Any SAE 
• Related SAE 
• SAE leading to death 
• AEs leading to dose delays or dose reduction 
• AE leading to permanent discontinuation-of-treatment 
Moreover, the number and percentage of patients with any AE will be summarized by worst NCI 
CTCAE grade by PT nested within SOC. 
Laboratory Assessments 
Clinical laboratory data to be summarized include hematology, blood chemistry, and urinalysis. 
The clinical laboratory parameters to be assessed are listed in Section 10.2 and the scheduled 
time points for assessment are tabulated in the SoA. 


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Clinical laboratory parameters at each time point and change from baseline to each post-baseline 
time point will be summarized using descriptive summary statistics for each parameter by 
treatment group.  
Clinical laboratory results will be classified according to of NCI CTCAE v5.0. Laboratory 
results not corresponding to an NCI CTCAE term will not be graded. Shift tables from baseline 
to worst grade on-treatment will be provided for each laboratory parameter.  
Vital Signs 
Vital sign parameters and the scheduled time points for assessment are presented in the SoA.  
Vital sign parameters at each time point and change from baseline to each post-baseline time 
point will be summarized using descriptive summary statistics for each parameter by treatment 
group.  
ECG 
ECGs parameters and the scheduled time points for assessment are presented in the SoA. 
ECGs will be judged by the investigator as clinically significant (yes/no). The number and 
percentage of patients with clinically significant ECG findings will be summarized by treatment 
group for each time point. 
9.4.6. 
Other Analyses 
Biomarker Analyses 
Cellular immune responses, cytokines, and further immunological parameters as represented in 
SoA will be analyzed using the pharmacodynamics analysis set. Details of these analyses will be 
presented in the SAP. 
Other analyses may include analyses of assessments, which are not defined as endpoints, that 
need to be pre-specified and not necessarily be reported in the clinical trial report such as, but not 
limited to, immunogenicity, biomarkers, population pharmacokinetics, health care utilization 
endpoints and health technology assessment related endpoints. 
9.5. 
Interim and Final Analyses  
An interim statistical analysis for futility is planned for Arm 1A and Arm 1B based on the 
Simon's two-stage design (Simon, 198931) (see Section 9.2).  
The interim analysis will be performed based on all available data from a clinical data cut-off 
that will occur when the required number of patients in the respective arm have performed the 
first post-baseline tumor assessment or have been diagnosed with unequivocal clinical 
progression. 
The final analysis of the trial will be performed based on all available data from a clinical data 
cut-off that will occur after patients in the respective setting of Part 2 (Arms 1A, 1B, and 2, 3, 
respectively) have completed 8 cycles of treatment or discontinued. An analysis update will be 
performed when the last patient discontinues from the trial. 
9.6. 
Data Monitoring Committee/Safety Review Committee 
An Independent Data Monitoring Committee is not planned for this trial.  


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The patient’s safety will be monitored throughout the trial by the SRC. The SRC will be chaired 
by the sponsor’s MM and membership will include at a minimum the trial principal 
investigators, members of the sponsor medical and safety departments, as well as additional staff 
as appropriate. Please refer to the current SRC charter. 
10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This trial will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines 
• Applicable ICH GCP Guidelines 
• Applicable laws and regulations 
The clinical trial 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 substantial 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 patients. 
The investigator will be responsible for the following: 
• 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. 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
• Providing oversight of the conduct of the trial at the site and adherence to requirements of 
21 Code of Federal Regulation (CFR), ICH guidelines, the IRB/IEC, European 
Regulation 536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
10.1.2. 
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. 


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10.1.3. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the trial to the patient or his 
legally authorized representative and answer all questions regarding the trial. 
Patients must be informed that their participation is voluntary. Patients or their legally authorized 
representative (if applicable) will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act requirements, where applicable, and the IRB/IEC or trial center. 
The medical record must include a statement that written informed consent was obtained before 
the patient was enrolled in the trial and the date the written consent was obtained. The authorized 
person obtaining the informed consent must also sign the ICF. 
Patients must be re-consented 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 patient or the patient’s legally authorized 
representative. 
Separate ICFs will be used in this trial: 
• Main ICF for trial participation of mCRPC patients (Part 1 and Part 2 Arms 1A and 1B)  
• Main ICF for trial participation of LPC patients including mandatory tumor tissue sample 
(Part 2 Arms 2 and 3) 
• Pregnant partner ICF 
• Additional ICFs will be used if required by local regulations 
• Optional (in main ICF): tumor sample ICF (Patients in Part 1 and Part 2 Arms 1A and 1B 
will be asked if they are willing to provide optional tumor biopsy sample(s) in case these 
are taken at the time of disease progression) 
• Optional (in main ICF): Under certain circumstances the collection of additional blood 
samples might be indicated for a given patient 
• Optional ICF for trial participation of mCRPC patients in Arm 1B who wish to be treated 
with cemiplimab monotherapy following progression after to BNT112 monotherapy 
10.1.4. 
Data Protection 
During data entry, processing and analysis by the sponsor or designated CRO, all requirements 
of the data protection act will be taken into account. Access to data is strictly limited to 
authorized persons. Data are protected against unauthorized access according to current federal 
legislation and regulations. 
The sponsor will ensure that all safeguards are in place to minimize any eventual risk of 
breaches, and complies otherwise with the requirements of EU General Data Protection 
Regulation (GDPR Regulation [EU] 2016/679). The sponsor will regularly check all procedures 
relevant to the processing of personal data, as to ensure privacy by design and compliance with 
GDPR. 


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Patients will be assigned a unique identifier by the investigator according to the sponsor 
specifications on unique identifier assignment. Any patient records or datasets that are 
transferred to the sponsor will contain the identifier only; patient names or any information 
which would make the patient identifiable will not be transferred. 
The patient 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 
patient who will be required to give consent for their data to be used as described in the informed 
consent. 
The patient must be informed that his medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
In this clinical trial, an SRC is being implemented. For further details, see the SRC charter. 
10.1.6. 
Dissemination of Clinical Trial Data 
A final report integrating all trial results will be prepared by the sponsor.  
This trial will be registered and trials results be publicly posted on publicly accessible trial 
registries (e.g., ClinicalTrials.gov, EudraCT) in accordance with the applicable regulations. 
10.1.7. 
Data Quality Assurance 
All patient data relating to the trial will be recorded on printed or eCRF unless transmitted to the 
sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
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 (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 non-compliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided 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 parties 
(e.g., CROs). 
Trial monitors will perform ongoing source data verification to confirm that data entered into the 
eCRF by authorized site personnel are accurate, complete, and verifiable from source documents; 
that the safety and rights of patients are being protected; and that the trial is being conducted in 
accordance with the currently approved protocol and any other trial agreements, ICH GCP, and 
all applicable regulatory requirements. 


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Records and documents, including signed ICFs, pertaining to the conduct of this trial must be 
retained by the investigator for 30 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. 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. Source documents are filed at the investigator’s site. 
Data 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. 
10.1.9. 
Trial and Site Start and Closure 
The trial start date is the date on which the clinical trial will be open for enrollment of patients. 
The sponsor or applicable health authority may terminate the trial for reasonable cause.  
Trial centers will be closed upon trial completion. A trial center 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 center by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Discovery of an unexpected, serious or unacceptable risk to patients enrolled in the trial.  
• Inadequate recruitment of patients by the investigator. 
• Discontinuation of further trial treatment development. 
The sponsor or health authority may terminate the trial for reasonable cause. Conditions that may 
warrant termination of the trial include, but are not limited to: 
• Discovery of an unexpected, serious or unacceptable risk to patients enrolled in the trial. 
• Sponsor decision to suspend or discontinue testing, evaluation, or development of the 
trial drug. 
• Failure of the investigator to comply with the approved clinical trial protocol, pertinent 
guidelines, and or regulations. 
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 organization(s) 
used in the trial of the reason for termination or suspension, as specified by the applicable 


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regulatory requirements. The investigator shall promptly inform the patient and should assure 
appropriate patient therapy and/or follow-up. 
10.1.10. 
Publication Policy 
The results of this trial may be published or presented at scientific meetings. If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. 
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of trial results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
For further details, please refer to the Laboratory Manual provided by the central laboratory. 
 
Table 10-1: 
Local Safety Laboratory Tests (Blood and Urine) - Overview 
Parameters (by group) 
Hematology: 
Hemoglobin, hematocrit, red blood cell count, white blood cell count and differential (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils), platelet count 
Coagulation: 
International normalized ratio, activated partial thromboplastin time, fibrinogen 
Blood chemistry: 
Alkaline phosphatase (ALP), creatinine, ferritin, C-reactive protein, albumin, alanine aminotransferase 
(ALT), amylase, aspartate aminotransferase (AST), gamma glutamyl transpeptidase, total bilirubin, 
blood urea nitrogen, glucose, lipase, sodium, potassium, calcium, and thyroid function (thyroid 
stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) 
Urinalysis: 
Dipstick: specific gravity, pH, glucose, protein, ketones, blood  
Microscopic urinalysis: If warranted by dipstick results, urine sediment will be microscopically 
examined for presence of red blood cells, white blood cells, casts, crystals, epithelial cells, and bacteria 
Circulating tumor cells 
 
Table 10-2: 
Central Blood Biomarker Assessment - Overview 
Rationale 
Test 
Eligibility 
Testosterone 
Eligibility 
Serology i.e., HBsAG, anti-HBc, anti-HBs, anti-HCV, anti-HIV 1/2 
Safety 
Cytokines 
MoA/PD 
PSA 
MoA/PD 
Antigen-specific T cells (ELISpot and further immune monitoring) 
MoA/PD 
HLA typing 
MoA/PD 
TCR profiling  
ELISpot = enzyme linked immunospot (assay); HBc = hepatitis B core antigen; HBs = hepatitis B surface antigen; HBsAG = 
hepatitis surface antigen; HCV = hepatitis C virus; HLA = human leukocyte antigen; ICS = intracellular cytokine staining; 
MoA/PD = mechanism of action/pharmacodynamics; TCR = T cell receptor. 
 
Please refer to the trial-specific Laboratory Manual for further details. 
 


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10.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a patient or clinical trial patient, 
administered a pharmaceutical product and which does not necessarily have to have a 
causal relationship with this treatment. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 
• A TEAE is defined as any AE with an onset date on or after the first administration of 
IMP (if the AE was absent before the first administration of IMP) or worsened after the 
first administration of IMP (if the AE was present before the first administration of 
IMP). AEs with an onset date more than 30 days or 90 days, respectively (and at 
screening for all patients if the patient is not yet randomized), after the last 
administration of IMP will be considered as treatment-emergent only if assessed as 
related to the IMP by the investigator. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after trial treatment administration even though it 
may have been present before the start of the trial. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either trial 
treatment or a concomitant treatment. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
• The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be 
reported as AE or SAE if they fulfill the definition of an AE or SAE. “Lack of efficacy” 
or “failure of expected pharmacological action” will not be reported as an AE or SAE. 
 


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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the patient’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the patient’s 
condition. However, specific symptoms at time of progression that are considered that 
may be caused by other reason, and fatal cases where other reason rather than the PD 
may not be discarded, will have to be documented as AEs and reported as SAEs if 
applicable. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 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. 
• DREs and/or disease-related outcomes not qualifying as AEs or SAEs are further 
specified in Section 8.4.7. 
 
 


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Adverse Reaction (AR) 
• All untoward and unintended responses to an IMP related to any dose administered. 
• The definition covers also medication errors and uses outside what is foreseen in the 
protocol, including misuse and abuse of the product. 
• The definition implies a reasonable possibility of a causal relationship between the event 
and the IMP. This means that there are facts (evidence) or arguments to suggest a causal 
relationship. 
10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.  
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the patient 
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. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the patient has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When 
in doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle) which may interfere with or prevent everyday 
life functions but do not constitute a substantial disruption. 


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e. 
Is a congenital anomaly/birth defect 
f. 
Is another medically important condition: 
• Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
patient or may require medical or surgical treatment to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
• 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse. 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an 
AE (e.g., rated as mild, moderate, or severe, or according to NCI CTCAE; see Section 10.3.3; 
the event itself may be of relatively minor medical significance (such as severe headache 
without any further findings). 
Severity and seriousness need to be assessed independently for each AE recorded on the 
eCRF. 
SAEs are required to be reported by the investigator to the sponsor immediately (i.e., no more 
than 24 h after learning of the event; see Section 10.3.4 for reporting instructions). 
 
SUSARs 
Any serious adverse reaction that is classified as unexpected by the sponsor. 
An AR is classified as unexpected when the nature or severity is not consistent with the 
applicable product information (reference safety information [RSI], i.e., IB for an 
unauthorized investigational product or SmPC for an authorized product). The term severity is 
used here to describe the intensity of a specific event. This has to be distinguished from the 
term serious. 
The expectedness of an AR is determined by the sponsor according to the RSI. This should be 
done from the perspective of events previously observed, not based on what might be 
anticipated from the pharmacological properties of a medicinal product. 
If the RSI is contained in an IB, the IB should contain a clearly identified section to expected 
ARs. 


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10.3.3. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
The investigator needs to assess and document any AE regardless of association with the use 
of the trial treatment during the period of observation (from signing ICF until FU-D30 for 
Part 1 and Part 2 Arm 1B and Arm 3, and FU-D90 visit for Part 2 Arm 1A, Arm 1B switch-
over patients, and Arm 2). 
• Data pertaining to AEs will be collected during each trial visit either. Based on the 
patient’s spontaneous description or investigator’s inquiry or discovered in the course of 
examinations done during the visit, clinical significance of any sign or symptom needs 
to be evaluated by the investigator.  
• Clinically significant findings need to be documented as AEs in the source data and 
eCRF. Findings that are evaluated and documented in the source data as not clinically 
significant (e.g., an abnormal laboratory value without any clinical manifestation), 
should not be documented as AE. 
• The investigator will then record all relevant AE information in the eCRF and perform 
an assessment on: 
o Intensity according to CTCAE v5.0  
o Seriousness 
o Outcome 
o Drug relationship of the AE to the trial treatment 
o Any trial treatment action and/or any other action taken 
• All assessments as well as AE term (diagnosis/description), start date and time of onset, 
end date and time need to be documented on the source data and eCRF.  
• It is not acceptable for the investigator to send photocopies of the patient’s medical 
records to the sponsor in lieu of completion of the AE eCRF page. 
• There may be instances when copies of medical records for certain cases are requested 
by the sponsor. In this case, all patient identifiers, with the exception of the patient 
number, will be redacted on the copies of the medical records before submission to the 
sponsor. 
• To avoid colloquial expressions, the AE should be reported in standard medical 
terminology. The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE. If a definitive 
diagnosis is not possible, the individual signs and symptoms should be recorded. 
 
 


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Assessment of Intensity 
The intensity of an AE (i.e., severity of organ toxicity) will be graded according to the NCI 
CTCAE v5.0. AEs that are not listed in CTCAE v5.0 should be classified according to the 
investigator’s discretion as close as possible to CTCAE v5.0, based on the comparison with 
the most severe case encountered in past training and clinical experience.  
The investigator will make an assessment of intensity for each AE and SAE reported during 
the trial and assign it to one of the following categories:  
• Grade 1 - Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. An event that is easily tolerated by the patient, causing 
minimal discomfort and not interfering with everyday activities. 
• Grade 2 - Moderate: Minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*. An event that causes 
sufficient discomfort and interferes with normal everyday activities. 
• Grade 3 - Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting of self-
care ADL**. An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
• Grade 4 - Life-threatening consequences; urgent intervention indicated 
• Grade 5 - Death related to AE 
* Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money etc. 
** Self-care ADL refer to bathing, dressing, and undressing, feeding self, using the toilet, 
taking medications, and not bedridden. 
With regards the intensity of an AE the following needs to be documented in source data and 
eCRF: 
• Initial intensity of the AE 
• Maximum intensity of the AE 
• For each change of intensity: 
o New grade of intensity 
o Date of change (= start of new grade of intensity) 
o Time of change (only if relevant) 
A change of intensity only needs to be documented if there is a clearly definable change in 
grading of the AE (e.g., a laboratory result changes from severe to moderate according to 
CTCAE criteria). 
An event is defined as “serious” when it meets at least one of the predefined seriousness 
criteria as described in the definition of an SAE, NOT when it is rated as severe.  


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Actions taken by the investigator 
Actions taken by the investigator as a result of an AE have to be documented.  
Action(s) taken with trial treatment (IMPs) by the investigator: 
• Dose not changed (= continuation of trial treatment administration according to the trial 
protocol) 
• Dose reduced (= reduction of the trial treatment dosage *) 
• Trial treatment withdrawn temporarily (= interruption and resumption); i.e.: 
o Delayed administration of IMP within one vaccination cycle 
o Delayed start of the next vaccination cycle 
o Cancellation of administration at a given visit 
o Interruption of IMP administration during a given visit  
• Trial treatment permanently withdrawn (= discontinuation) 
• Unknown (e.g., in case the patient is lost to follow-up) 
• Not applicable (e.g., in case treatment with trial treatment has not yet started or event 
starts after last trial treatment administration)  
*If an increase of trial treatment dosage is intended according to the trial protocol and the 
dosage is kept in comparison to last administration of trial treatment, it needs to be 
documented as “Dose reduced.” 
Other action(s) that may be taken by the investigator include: 
• None 
• Initiation of a concomitant therapy for the treatment of the AE 
• Termination of a concomitant treatment (please specify; e.g., if this might be the cause 
of the AE) 
• Change of the dose of a concomitant treatment 
• Hospitalization or prolongation of hospitalization (please complete SAE-Form) 
• Initiation/termination of a non-drug therapy 
• Other (please specify) 
 
Outcome 
The investigator has to assess the outcome of an AE (and not the patient’s outcome) at the 
time of documentation based on the following criteria: 
• Recovered/resolved* (= complete resolution of the AE) 
• Recovering/resolving (= AEs which are improving but not yet resolved completely, e.g., 
decrease in an intensity grade) 
• Not recovered/not resolved (= AEs which are ongoing without improving or still present 
when the patient deceases due to another cause) 


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• Recovered/resolved with sequelae* (= patient recuperated but retained pathological 
conditions resulting from the AE; the sequelae should be indicated) 
• Fatal** (= death due to the AE) 
• Unknown (e.g., in case the patient is lost to follow-up) 
* Generally, an AE is defined as recovered/resolved if all symptoms have ceased, no 
medication for treatment of the event is taken anymore and no other measures (e.g., 
hospitalization) are ongoing.   
If the patient has developed permanent or chronic symptoms or if the event requires long-term 
medication(s), the AE is defined as recovered/resolved with sequelae as soon as no changes of 
symptoms and/or medication(s) are expected anymore.  
An AE that is documented as a worsening of a medical condition already known at baseline, is 
defined as recovered as soon as the medical condition has returned to baseline status. 
** In case of a fatal event, the event term should not be “death” but the underlying event 
which led to death (death = outcome). If there is more than one AE in a fatal case, only the AE 
leading to death will be attributed with the outcome “fatal”. All other AEs ongoing at the time 
of death will be attributed with the outcome “not recovered/not resolved”. A copy of an 
autopsy report should be submitted if available. 
All ongoing AEs will be followed until resolution, considered by the investigator to be stable 
or chronic (resolved with sequelae), new systemic anti-cancer treatment (outside the protocol) 
is initiated, the patient is lost to follow-up or the patient withdraws consent. If no final status is 
reached at Safety FU-D30 (for all Part 1 patients and Part 2 Arm 1B and Arm 3) or Safety 
FU-D90 visit (for Part 2 Arm 1A, Arm 1B switch-over patients, and Arm 2), the investigator 
must confirm the unavailability of a final status. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between trial treatment/trial 
procedure and each occurrence of each AE/SAE. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to trial treatment administration 
will be considered and investigated. 
• The following table can be taken as guidance: 
 
Causality Term 
Assessment Criteria 
Assessed as 
Certain 
• 
Event or laboratory test abnormality, with plausible 
time relationship to drug intake  
• 
Cannot be explained by disease or other drugs  
• 
Response to withdrawal plausible (pharmacologically, 
pathologically)  
Related 


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• 
Event definitive pharmacologically or 
phenomenologically (i.e., an objective and specific 
medical disorder or a recognized pharmacological 
phenomenon)  
• 
Rechallenge satisfactory, if necessary  
Probable/ 
Likely 
• 
Event or laboratory test abnormality, with reasonable 
time relationship to drug intake  
• 
Unlikely to be attributed to disease or other drugs  
• 
Response to withdrawal clinically reasonable  
• 
Rechallenge not required  
Related 
Possible 
• 
Event or laboratory test abnormality, with reasonable 
time relationship to drug intake  
• 
Could also be explained by disease or other drugs  
• 
Information on drug withdrawal may be lacking or 
unclear  
Related 
Unlikely 
• 
Event or laboratory test abnormality, with a time to 
drug intake that makes a relationship improbable (but 
not impossible)  
• 
Disease or other drugs provide plausible explanations  
Not related 
It is sufficient to document the causality in the source data and eCRF as: 
• Related, or 
• Not related. 
For an event considered “related to trial treatment” there is a reasonable possibility of a 
causal relationship.  
For an event considered “not related to trial treatment” there is no reasonable possibility of a 
causal relationship. 
Relationship to trial treatment (BNT112 and Cemiplimab) 
• The relationship or association of an AE or SAE to a trial treatment will be made by the 
investigator after having evaluated all accessible data and, if necessary, he/she will re-
evaluate the case as new information becomes available. Events caused by the procedure 
of trial treatment administration should be differentiated from events caused by the trial 
treatment itself. Only events suspected to be caused by the IMPs itself should be 
documented as ADRs but not events caused by the NIMP or the procedure of trial 
treatment administration 
Relationship to trial procedures 
• In this first-in-human trial, it cannot be excluded that during the course of the trial some 
procedures give rise to AEs which are related to the trial procedure and not to the trial 


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treatment. Procedure related AE can occur at the site of injection of the trial treatment 
e.g., redness, swelling, hematoma or itching or during or after trial-specific procedure, 
e.g., discomfort after blood drawing. These events have to be reported in the eCRF on 
Adverse Event pages as “related to trial procedure” with the causing procedure 
specified. The intensity of these AEs will be characterized according to the NCI CTCAE 
v5.0. 
Relationship to prostate cancer surgery 
• For patients in Part 2 Arms 2 and 3 the investigator should also assess the relationship of 
the event to the prostate cancer surgery. These events have to be reported in the eCRF 
on Adverse Event pages as “related to prostate cancer surgery”. 
• The investigator will also consult the respective IB and/or Product Information, for 
marketed products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important 
that the investigator always makes an assessment of causality for every event before the 
initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
SAE Exemptions 
In general, SAEs are defined according to ICH Topic E2A (CPMP/ICH/377/95), EU Directive 
2001/20/EC and ENTR/CT-3 (see Section 10.3.2). In the present trial, some events are 
excluded from the SAE definition. The following events do not need to be reported as SAEs: 
• AEs and SAEs occurring later than 30 days (for Part 1 and Part 2 Arm 1B and Arm 3) 
and 90 days (for Part 2 Arm 1A, Arm 1B switch-over patients, and Arm 2) after the last 
administration of trial medication must only be reported by the investigator to the 
sponsor if a relationship to trial treatment or trial procedure is suspected. 
• Hospitalizations for respite care will not be considered as reportable SAE. 
• Hospitalizations solely for coordination of care, including hospice arrangements, will 
not be considered as reportable SAE. 
• Hospitalizations that were necessary solely because of patient requirement for outpatient 
care outside of normal outpatient clinic operating hours will not be considered as 
reportable SAE. 


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• Planned hospitalizations required by the protocol (e.g., for trial treatment administration 
or insertion of access device for trial treatment administration) will not be considered as 
reportable SAE. 
• Hospitalizations for procedures or interventions of a pre-existing condition of the patient 
(elective surgery = planned, non-emergency surgical procedure) will not be considered 
as a reportable SAE (e.g., prostate cancer surgery planned for patients in Part 2 Arms 2 
and 3) 
o if it was planned and documented in patient record before the trial-specific 
patient informed consent was signed (ICF for trial participation, see 
Section 10.1.3, or 
o if it was scheduled during the trial when elective surgery became necessary and 
the patient has not experienced an AE. 
Nevertheless, this kind of hospitalization should be avoided during trial treatment. 
• Hospitalization of a patient for monitoring and symptomatic treatment for up to 24 h 
due to a transient inflammatory reaction of Grade 1 or 2 will not be considered as a 
SAE (but needs to be documented as AE). 
• The progression of underlying disease (e.g., new metastases, increase of PSA value) 
during trial participation is not considered as AE. However, specific symptoms at time 
of progression that are considered that may be caused by other reasons, and fatal cases 
where other reasons rather than the PD may not be discarded, will have to be 
documented as AEs and reported as SAEs if applicable. 
• Routine treatment or monitoring of the underlying disease not associated with any 
deterioration in the patient’s condition 
 
Documentation of particular situations 
AEs that are secondary to other events: 
In general, AEs that are secondary to other events (e.g., cascade events or clinical sequelae) 
should be identified by their primary cause, with the exception of severe or serious secondary 
events. A medically significant secondary AE that is separated in time from the initiating event 
should be documented as an independent AE in source data and eCRF. For example: 
• If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be documented as AE. 
• If vomiting results in severe dehydration, both events should be documented as AEs 
separately. 
Abnormal laboratory results and vital signs values: 


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Not every laboratory or vital signs abnormality needs to be documented as AE. For clinically 
significant laboratory/vital signs abnormalities the following definitions and documentation 
rules apply: 
• If a laboratory/vital signs abnormality is a sign of a disease or syndrome, the 
laboratory/vital signs abnormality is clinically significant and only the diagnosis of the 
causing disease or syndrome needs to be documented as AE. 
• If a laboratory/vital signs abnormality results in specific symptoms but no diagnosis of a 
disease or syndrome can be made, the laboratory/vital signs abnormality is clinically 
significant and only the symptoms need to be documented as AEs. 
If a laboratory/vital signs abnormality is not a sign of a disease or syndrome and does not 
result in specific symptoms but leads to a change in trial treatment or in a medical 
intervention, the laboratory/vital signs abnormality is clinically significant and must be 
documented as AE. 
Death: 
• Any death that occurs within the observation period will be reported as an SAE. 
Exemptions to the SAE definition as defined above do also apply for fatal cases. A copy 
of an autopsy report should be submitted if available. Date and cause of death will be 
recorded. 
• In case of a fatal event, the event term should not be “death” but the underlying event 
which led to death (death = outcome). If there is more than one AE in a fatal case, only 
for the AE leading to death the outcome “fatal” should be selected. If the cause of death 
is unknown and cannot be ascertained at the time of reporting, “unexplained death” 
should be documented as event term. 
• In addition to reporting as SAE, the death page of the eCRF needs to be completed. 
AEs associated with an overdose or error in drug administration: 
An overdose is the accidental or intentional use of a drug in an amount (per administration or 
cumulatively) higher than the dose being studied (for the trial treatment) or higher than the 
maximum recommended dose according to the authorized product information (for approved 
concomitant treatments). An overdose or incorrect administration of a drug is not itself an AE, 
but it may result in an AE.  
All AEs associated with an overdose or incorrect administration should be documented as AE 
in source data and eCRF and reported as SAE if applicable. 
 
Follow-up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the sponsor 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 


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• If a patient dies during participation in the trial or during a recognized follow-up period, 
the investigator will provide the sponsor with a copy of any post-mortem findings 
including histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 
• The investigator will submit any updated SAE data to the sponsor within 24 h of receipt 
of the information as described in Section 10.3.4. 
10.3.4. 
Reporting of SAEs 
SAE Reporting to Sponsor 
The period of observation for each patient extends from signing ICF until Safety FU-D30 
(for all Part 1 patients and Part 2 Arm 1B and Arm 3) or Safety FU-D90 visit (for Part 2 
Arm 1A, Arm 1B switch-over patients, and Arm 2).  
All SAEs which occur in a patient during the observation period, whether considered to be 
associated with trial medication or not, must be reported by the investigator to the sponsor 
immediately but at the latest within 24 h following knowledge of the event.  
All SAEs occurring after the end of the period of observation only have to be reported to the 
sponsor if the investigator suspects a relationship to trial medication or the trial procedure. 
The investigator needs to complete the paper Serious Adverse Event Form which has to be 
sent to the sponsor via one of the following reporting lines: 
Safety Report Fax No.:  
 
Safety Report E-Mail Address:  
Information for final description and evaluation of a case report may not be available within 
the required time frames for reporting. Nevertheless, for regulatory purposes, initial reports 
should be submitted if the following minimal information is available:  
• An identifiable patient (patient number) 
• A suspected medicinal product  
• An identifiable reporting source (investigator/trial center identification)  
• An event or outcome that can be identified as serious 
SAE follow-up information should be sent to the sponsor (indicating that this is a “follow-up” 
report) without delay as described above and accompanied by appropriate anonymous 
supporting documentation (e.g., discharge letters, medical reports or death certificates), until a 
final outcome and date are available. All confidential information (name, address, full day of 
birth) needs to be blackened before sending. In addition to a medical record, the investigator 
should complete an Additional Information and Follow-Up Form, which contains the SAE 
term and patient number. 


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A copy of the submitted SAE report must be retained on file by the investigator. If explicitly 
required according to national legislation, the investigator must submit copies of the SAEs to 
the IRB/IEC or authority and retain documentation of these submissions in the Site Trial File. 
In case an investigator or any other trial team member has questions on safety reporting to the 
sponsor, these can be addressed to: 
E-Mail:
Please note that for medical questions the MM for this trial should be contacted. 


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10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Contraception Guidance 
After signing the ICF, patients who are sexually active with a woman of childbearing potential 
must agree to use a condom with spermicidal foam/gel/film/cream/suppository. Additionally, 
patients or their partners are required to use at least one form of highly effective contraception 
for the time period between signing the ICF and 90 days after the last administration of BNT112 
OR for 6 months after the last dose of cemiplimab. Highly effective contraception methods are 
listed in Table 10-3. Birth control methods are considered highly effective if they have a failure 
rate of less than 1% per year, when used consistently and correctly.  
All patients must also not donate sperm during the trial starting after signing the ICF and for 90 
days after receiving the last dose of BNT112 OR for 6 months after receiving the last dose of 
cemiplimab. 
 
Table 10-3: 
Highly Effective Methods of Contraception 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation1 (oral, intravaginal, or transdermal) in combination with a barrier method 
or/and an intrauterine device 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation1 (oral, injectable, 
or implantable) in combination with a barrier method or/and an intrauterine device 
• 
Intrauterine device2 
• 
Intrauterine hormone-releasing system2 
• 
Bilateral tubal occlusion2 
• 
Vasectomized partner2, 3 
• 
Sexual abstinence4 
1. Hormonal contraception may be susceptible to interaction with some concomitant medications, which may 
reduce the efficacy of the contraception method. 
2. Contraception methods that in the context of this guidance are considered to have low user dependency. 
3. Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the woman of childbearing potential (trial patient) and that the vasectomized partner has received medical 
assessment of the surgical success. 
4. In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the trial treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the patient. 
Table adapted from ‘Recommendations related to contraception and pregnancy testing in clinical trials. Advisory 
non-binding guidance represented at the CTFG-meeting in Rome 201440. 
 
 


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Collection of Pregnancy Information 
Male patients with partners who become pregnant 
• The investigator will attempt to collect pregnancy information on any male patient’s 
female partner who becomes pregnant after the male patient’s start of trial treatment and 
until 90 days after the last dose of BNT112 and 6 months after the last dose of 
cemiplimab. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the paper-based 
Pregnancy Reporting Form and submit it to the sponsor within 24 h of learning of the 
partner’s pregnancy. The completed form needs to be sent to the Safety Report Fax 
number or E-Mail Address mentioned in Section 10.3.4. The female partner will also be 
followed to determine the outcome of the pregnancy, including any voluntary or 
spontaneous termination, details of the birth, the presence or absence of any congenital 
abnormalities, birth defects, maternal or newborn complications and their presumed 
relation to the trial treatment.  
10.5. 
Appendix 5: 
Declaration of Helsinki 
World Medical Association (WMA) Declaration of Helsinki - Ethical Principles for Medical 
Research Involving Human Subjects. Adopted by the 18th WMA General Assembly, Helsinki, 
Finland, June 1964 and amended by the 64th WMA General Assembly, Fortaleza, Brazil, 
October 2013.  
 


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10.6. 
Appendix 6: 
ECOG PS 
Developed by the Eastern Cooperative Oncology Group, Robert L. Comis, MD, Group Chair.* 
The Eastern Cooperative Oncology Group is now part of the ECOG-ACRIN Cancer Research 
Group. 
 
Table 10-4: 
ECOG PS 
GRADE ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
*Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology 
Group. Am J Clin Oncol. 1982; 5: 649-655. 
Available from: https://ecog-acrin.org/resources/ecog-performance-status. 
 


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10.7. 
Appendix 7: Graphical Illustration of PSA Progression for Trial 
Eligibility 
 
 
Figure 10-1: Graphical Illustration of PSA Progression for Trial Eligibility 
 
The Prostate Cancer Working Group Criteria 329 states that for PSA eligibility for a trial there 
should be 2 sequential rises (value in Week 5 and 6A) in PSA above the baseline (seen above at 
Week 4) separated by ≥ 1 week with the baseline PSA being above 2 ng/mL. If after 1 rise in 
PSA there is a decrease with the value remaining above baseline (e.g., 6B), a further rise is 
required (as seen in Week 7). 
10.8. 
Appendix 8: 
Consensus Grading for Cytokine Release Syndrome 
 
Table 10-5: 
ASTCT CRS Consensus grading 
CRS parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fevera 
Temperature 
≥38°C 
Temperature 
≥38°C 
Temperature ≥38°C 
Temperature ≥38°C 
 
 
 
With 
 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring a vasopressor 
with or without 
vasopressin 
Requiring multiple 
vasopressors (excluding 
vasopressin) 
 
 
 
And/orb 
 
Hypoxia 
None 
Requiring low-
flow nasal 
cannulac or blow-
by 
Requiring high-flow 
nasal cannulac, facemask, 
nonrebreather mask, or 
Venturi mask 
Requiring positive 
pressure (e.g., CPAP, 
BiPAP, intubation and 
mechanical ventilation) 
Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS grading. 


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a. 
Fever is defined as temperature ≥38°C not attributable to any other cause. In patients who have CRS then receive 
antipyretic or anti-cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS 
severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
b. 
CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5°C, hypotension requiring one vasopressor, and hypoxia requiring low-flow 
nasal cannula is classified as Grade 3 CRS. 
c. 
Low-flow nasal cannula is defined as oxygen delivered at ≤6 L/minute. Low-flow also includes blow-by oxygen delivery, 
sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at >6 L/minute. 
ASTCT = American Society for Transplantation and Cellular Therapy; BiPAP = Bilevel Positive Airway Pressure; 
CPAP = continuous positive airway pressure; CRS = cytokine release syndrome; CTCAE = Common Terminology Criteria for 
Adverse Events. 
Source: Lee et al. 2019.19 
 
10.9. 
Appendix 9: 
Criteria for Disease Response Assessment 
 
1. MEASURES OF PROGRESSION AFTER COMMENCMENT OF TREATMENT: 
Progression will be documented by confirmed radiograph progression (bone and/or CT/MRI 
scan with a subsequent confirmatory scan) and/or unequivocal clinical progression. Patients 
should not discontinue treatment on the basis of PSA progression alone and instead this 
should guide the investigator to potentially expedite radiological investigations.  
The criteria for disease progression are considered met if one or more of the following conditions 
occur:  
a) Radiological progression per PCWG3: 
• Soft tissue/visceral disease progression: 
− A patient will be determined to have progressed if they have progression of target 
lesions (sum of diameter increase to nadir of ≥20% and by ≥5 mm), clear progression 
of existing non-target lesions, or the appearance of 1 or more new lesions. Lymph 
nodes have to be ≥ 1.5 cm in short axis to be deemed measurable. 
− The scan for confirmation of progression may be performed ≥4 and ≤8 weeks after the 
initial scan demonstrating progression. Patients who have a repeat scan earlier than 
scheduled and do not confirm progression do not need to undergo the next scheduled 
imaging if it is <4 weeks after the confirmation scan. Patients will return to their regular 
imaging schedule starting with the next time point. 
• Bone disease progression 
− On the C3D15 scan, ≥2 new lesions compared with baseline confirmed by a second 
scan ≥6 weeks later that also shows an additional ≥2 new bone lesions (2+2 rule, i.e., a 
total of ≥4 new lesions compared with the baseline bone scan). 
− On subsequent scans (>16 weeks), ≥2 new bone lesions compared with the previous 
scan with the confirmatory scan at ≥6 weeks demonstrating at least persistence of the 
progression noted on the previous scan. 
b) Unequivocal evidence of clinical progression 
c) PSA Progression 


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• ≥25% increase and an absolute ≥2 ng/mL rise This rise must be confirmed by a second 
measurement ≥3 weeks later and the date of progression is denoted as the first 
measurement to meet these criteria. Ignore early rises (before 12 weeks) in determining 
PSA progression. 
• If the PSA has risen during the first 12 weeks and then decreased, the ≥25% increase and 
an absolute ≥2 ng/mL rise is required above the new decreased value (nadir value), 
confirmed by a second measurement at least 3 weeks later. 
• If the PSA has risen during the first 12 weeks with no decline, the date of progression is 
backdated to the date when ≥25% increase and an absolute ≥2 ng/mL rise (from Baseline 
value) was first observed. 
2. MEASURES OF RESPONSE: 
The PCWG3 criteria for disease response in a patient are considered met if 1 or more of the 
following conditions occur:  
a) PSA response:  
• PR: ≥50% decline in PSA from baseline confirmed at least 4 weeks later 
• SD: Serial PSA measurements that do not meet the criteria for PR or PD 
b) Radiological response: 
• Soft tissue/visceral disease: 
− CR: Disappearance of all target lesions. A reduction in short axis to <10 mm must be 
seen in any pathological lymph nodes. No new lesions.  
− PR: 30% decrease in the sum of the longest diameter of target lesions. 
− SD: No evidence of PD, CR or PR. 
• Bone disease response 
− Bone scan is not used as part of the response criteria. Bone scans will be evaluated for 
progression only. 
c) Circulating tumor cell (CTC) response: 
• Conversion of CTC ≥5/7.5 mL to <5/7.5 mL at 9 weeks. If there is a CTC response, this 
must be confirmed by an additional <5/7.5 mL result at least 4 weeks later. 
 
 


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10.10. 
Appendix 10: Abbreviations 
 
Abbreviation 
Definition 
ADL 
Activities of daily living  
ADR 
Adverse drug reaction 
ADT 
Androgen-deprivation therapy  
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
APC 
Antigen presenting cell 
AR 
Adverse reaction 
AST 
Aspartate aminotransferase  
C 
Cycle 
CFR 
Code of Federal Regulation 
CR 
Complete response  
CRO 
Contract research organization  
CRPC 
Castration-resistant prostate cancer 
CRS 
Cytokine release syndrome  
CT 
Computed tomography 
CTC 
Circulating tumor cell 
CTCAE v5.0 
Common Terminology Criteria for Adverse Events, version 5.0  
CTLA-4  
Cytotoxic T-lymphocyte-associated protein 4 
D 
Day of cycle 
DFS 
Disease-free survival 
DI 
Dose intensity 
DL 
Dose level  
DLT 
Dose-limiting toxicity  
DoR 
Duration of response 
DRE 
Disease-related event 
ECG  
Electrocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
eCRF 
Electronic case report form 


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Abbreviation 
Definition 
EoT 
End of treatment 
EU 
European Union 
FU 
Follow-up (Visit) 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GLP 
Good Laboratory Practice 
h 
Hour(s) 
HPV 
Human papilloma virus 
IB 
Investigator’s Brochure  
ICF 
Informed consent form  
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use  
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IMP 
Investigational medicinal product 
IMP 1 
BNT112 
IMP 2 
Cemiplimab 
IRB 
Institutional Review Board 
iRECIST  
Immune-modified Response Evaluation Criteria in Solid Tumors 
ITT 
Intent-to-treat 
IV 
Intravenous(ly) 
LHRH 
Luteinizing hormone-releasing hormone 
LHRHa 
Luteinizing hormone-releasing hormone analogue 
LPC 
Localized prostate cancer  
mCRPC 
Metastatic castration-resistant prostate cancer  
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major histocompatibility complex 
MHRA 
Medicines & Healthcare products Regulatory Agency of the United 
Kingdom 
min 
Minute(s) 
mITT 
Modified intent-to-treat 


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Abbreviation 
Definition 
MM 
Medical Monitor 
MoA 
Mechanism (mode) of action 
mpMRI 
Multi-parametric MRI 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
mRNA (or RNA) 
Messenger ribonucleic acid 
NCI 
National Cancer Institute  
NIMP 
Non-investigational medicinal product  
NSAID 
Non-steroidal anti-inflammatory drug 
OR 
Objective response 
ORR 
Objective response rate 
OS 
Overall survival  
PAP 
Prostatic acid phosphatase 
PCWG3 
Prostate Cancer Working Group 3 
PD 
Progressive disease 
PD-1  
Programmed death receptor-1 
PD-L1 
Programmed cell death 1 ligand 1 
PFS 
Progression-free survival  
PO 
Oral(ly); per os 
PR 
Partial response 
PSA 
Prostate-specific antigen  
PSADT 
Prostate-specific antigen doubling time 
PT 
Preferred Term 
Q12W 
Every 12 weeks  
Q3W 
Every 3 weeks 
RDI 
Relative dose intensity  
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors, version 1.1 
REDR 
Recommended expansion dose range 
RNA-LPX  
Nanoparticulate formulation of lipid-complexed ribonucleic acid 
RSI 
Reference safety information  
SAE 
Serious adverse event 


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Abbreviation 
Definition 
SAP 
Statistical analysis plan  
SC  
Subcutaneous(ly) 
SCID 
Severe combined immunodeficiency 
SD 
Stable disease 
SmPC 
Summary of Product Characteristics 
SoA 
Schedule of activities 
SOC 
System Organ Class 
SRC 
Safety Review Committee 
SUSAR 
Suspected unexpected serious adverse reaction 
TAA 
Tumor-associated antigen 
TEAE 
Treatment-emergent adverse event 
TI 
Time index 
TLR 
Toll-like receptor  
TNBC 
Triple negative breast cancer 
TNRFSF9 
Tumor necrosis factor receptor superfamily member 9; 4-1BB; CD137 
TNM 
Tumor node metastasis 
ULN 
Upper limit of normal  
US FDA 
United States Food and Drug Administration 
USA 
United States of America 
W_pro1 
Previously used term for BNT112 cancer vaccine (BioNTech IMP) 
WMA 
World Medical Association 
 
 
 


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10.11. 
Appendix 11: Protocol Amendment History 
Changes made to the protocol using the substantial protocol amendments are described in detail 
in the document Protocol Amendment History which is available upon request. This Protocol 
Amendment History is filed together with the protocol in the trial master file.  
A comparison of the protocol after implementation of each amendment, e.g., a comparison 
between the protocol after amendment 1.0 and the protocol after implementation of amendment 
2.0, are available upon request. 
11. 
References 
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SAP_001.pdf: 
Page 1 of 107 
Confidentiality Statement: The information contained in this document is the property and copyright of 
BioNTech SE. Therefore, this document is provided in confidence to the recipient. No information contained 
herein shall be published, disclosed or reproduced without prior written approval of the proprietor(s). 
STATISTICAL ANALYSIS PLAN (SAP) 
RN5609C00/PRO-MERIT 
Version: 
Final v 2.0 
Date: 
27 APR 2023 
Sponsor: 
BioNTech SE 
Protocol number: 
RN5609C00 
Protocol title: 
First-in-human, dose titration and expansion trial to evaluate safety, 
immunogenicity and preliminary efficacy of W_pro1 (BNT112) monotherapy and in 
combination with cemiplimab in patients with prostate cancer 
Short Title / 
Acronym 
PRO-MERIT (Prostate Cancer Messenger RNA Immunotherapy) 
Trial Phase 
1/2A 
Protocol version: 
6.0 (including Amendments 1 to 5) 
Protocol date: 
23 FEB 2022 
Compounds: 
W_pro1, cemiplimab 
SAP version: 
Final v 2.0 
SAP date: 
27 Apr 2023 
CRO name: 
Syneos Health 
SAP author: 
PPD


BioNTech SE 
Confidential 
Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
Page 2 of 107 
Version: Final v 2.0 
Date: 27 APR 2023 
 
 
TABLE OF CONTENTS 
1 
SAP APPROVAL 
5 
2 
VERSION HISTORY 
6 
3 
INTRODUCTION 
7 
3.1 
Objectives and endpoints 
7 
3.2 
Trial design 
12 
3.3 
Schedule of activities 
20 
4 
STATISTICAL HYPOTHESES 
20 
5 
INTERIM ANALYSES AND ANALYSIS SEQUENCE 
20 
6 
SAMPLE SIZE DETERMINATION 
21 
7 
ANALYSIS SETS AND SUBGROUPS 
22 
7.1 
Analysis sets 
22 
7.2 
Protocol deviations 
23 
7.2.1 
Protocol deviations due to COVID-19 
24 
7.3 
Subgroups 
24 
8 
STATISTICAL ANALYSES 
25 
8.1 
General considerations 
25 
8.2 
Key definitions 
26 
8.3 
Missing Data 
33 
8.4 
Visit Windows 
33 
8.5 
Patient disposition 
33 
8.6 
Baseline characteristics 
34 
8.6.1 
Demographics 
34 
8.6.2 
Disease characteristics 
35 
8.6.3 
Prior anti-cancer treatments 
35 
8.6.4 
Prior and concomitant medication 
36 
8.6.5 
Other Procedures 
37 
8.6.6 
Medical history 
37 
8.7 
Efficacy analyses 
38 
8.7.1 
Primary analysis 
38 
8.7.2 
Supplementary analyses 
38 
8.7.3 
Secondary analyses 
38 
8.7.4 
Exploratory analyses 
40 
8.7.5 
Further efficacy analyses 
46 
8.7.6 
Interim analysis for futility 
46 
8.8 
Pharmacodynamic analyses 
47 
8.8.1 
Pharmacodynamic parameters 
47 
8.8.2 
Exploratory Biomarker Analyses 
48 


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8.9 
Safety analyses 
49 
8.9.1 
Primary safety endpoints dose-limiting toxicities and treatment-emergent 
adverse events 
49 
8.9.2 
Extent of exposure 
49 
8.9.3 
Adverse events 
51 
8.9.4 
Laboratory assessments 
58 
8.9.5 
Vital signs 
60 
8.9.6 
ECG 60 
8.9.7 
Physical examination 
61 
8.9.8 
ECOG PS 
61 
9 
QUALITY CONTROL 
63 
10 
PROGRAMMING CONSIDERATIONS 
64 
10.1 
General Considerations 
64 
10.2 
Table, Listing, and Figure Format 
64 
10.2.1 
General 
64 
10.2.2 
Headers 
64 
10.2.3 
Display Titles 
65 
10.2.4 
Column Headers 
65 
10.2.5 
Body of the Data Display 
65 
10.2.6 
Footnotes 
68 
11 
TABLE OF CONTENTS FOR TABLES, FIGURES AND LISTINGS 
69 
11.1.1 
Tables 
69 
11.1.2 
Listings 
82 
12 
REFERENCES 
85 
13 
SUPPORTING DOCUMENTATION 
85 
13.1 
Appendix 1: Changes to protocol-planned analyses 
86 
13.2 
Appendix 2: List of abbreviations 
87 
13.3 
Appendix 3: Best Overall Response derivation for iRECIST 
90 
13.4 
Appendix 4: Reporting conventions 
91 
13.5 
Appendix 5: Definition of visceral metastasis 
92 
13.6 
Appendix 5: Schedule of activities 
94 
13.7 
Appendix 6: Laboratory parameters to be categorized by Toxicity Grades 
(NCI CTCAE v5.0) 
106 
 
LIST OF TABLES 
Table 1:  SAP Version History Summary 
6 
Table 3-1:  Objectives and endpoints of the clinical trial 
7 
Table 8-1:  Biomarker Assessment - Overview 
48 


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Table 8-2:  Local Safety Laboratory Tests (Blood and Urine) - Overview 
59 
Table 8-3:  Normal Ranges for Vital Signs 
60 
 
LIST OF FIGURES 
Figure 3-1: 
Trial Design 
13 
 
 
 


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1 
SAP APPROVAL 
This SAP has been prepared, reviewed, and approved in accordance with the 
sponsor’s and Syneos Health standard operating procedures (SOP). Documentation 
of this process is filed in the trial master file (TMF). 
I confirm that I have reviewed this document and agree with the content. 
 
Approvals 
Syneos Health Approval 
  
Senior Principal Biostatistician 
 
 
 
Name, Title 
Lead  Biostatistician  
 
Signature 
 
Date (DD-Mmm-
YYYY) 
 
 
 
Name, Title 
Senior Reviewing Biostatistician 
 
 
Signature 
 
Date (DD-Mmm-
YYYY) 
BioNTech SE Approval 
Dr
  
 
 
 
Name, Title 
Sponsor Contact 
 
Signature 
 
Date (DD-Mmm-
YYYY) 
 
 
 
Name, Title 
Sponsor Contact 
 
 
Signature 
 
Date (DD-Mmm-
YYYY) 
 
 
 
Electronically signed by:
Reason: I am the author
Date: Apr 27, 2023 13:27 GMT+2
Electronically signed by
Reason: I am the review
Date: Apr 27, 2023 14:35 GMT+2
Electronically signed by:
Reason: I am the approve
Date: Apr 27, 2023 10:00 EDT
Electronically signed by:
Reason: I am the approver
Date: May 8, 2023 11:28 GMT+2
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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2 
VERSION HISTORY 
 
Table 1:  
SAP Version History Summary 
SAP version 
Approval date 
Document Owner 
Change 
Version 1.0 
18 OCT 2021 
Initial Release Version 
Version 2.0 
27 APR 2023 
Implementation of relevant 
changes for analyses based on 
new Protocol version V6.0: 
 
Change of the immunogenicity 
secondary endpoint to an 
exploratory immunogenicity 
endpoint (see Section 8.7.4). 
 
The schedule of assessment was 
adapted to allow for additional 
blood draws at C1D8, C1D15, 
C2D8, and C2D15 for prostate-
specific antigen level assessment. 
 
Final analysis for mCRPC patients 
and the final analysis of the LPC 
patients are planned to be 
performed separately (see 
modifications in Section 5). 
 
Further changes: 
Analysis set for all analyses related 
to PSA data changed. MITT set will 
be used instead of 
Pharmacodynamic set. 
 
 
 
 
PPD


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3 
INTRODUCTION 
This is a first-in-human, open-label, multicenter, dose titration and expansion four-
arm Phase I/IIa trial to evaluate the safety, tolerability, immunogenicity, and 
preliminary efficacy of W_pro1 cancer vaccine (W_pro1 or BNT112, which the 
company product name has been changed to in protocol RN5609C00, dated 23 FEB 
2022 (v6.0)) monotherapy or in combination with cemiplimab in patients with 
metastatic castration-resistant prostate cancer (mCRPC: Part 1 and Part 2 Arms 1A 
and 1B) and in patients with high-risk, localized prostate cancer (LPC) eligible for 
treatment with androgen-deprivation therapy (ADT) followed by radical 
prostatectomy (LPC: Part 2 Arms 2 and 3).  
The trial consists of two parts: Part 1 (dose titration) and Part 2 (dose expansion). 
The results might be included in a regulatory submission. 
This statistical analysis plan (SAP) describes the detailed procedures for the planned 
statistical analysis for protocol mentioned aboveto support the completion of the 
Clinical Trial Report (CTR). However, although the company product name has been 
changed to BNT112 in the current protocol, W_pro1 will remain unchanged in this 
SAP and other trial-related documentation. 
The purpose of this SAP is to define and describe the statistical methodologies that 
will be used, are complete and appropriate to allow valid conclusions regarding the 
trial objectives. 
Syneos Health will perform the statistical analyses (using SAS® software version 9.4 
or higher, and/or other statistical software as required) and is responsible for the 
production and quality control of all tables, figures and listings (TFLs). 
Templates for each unique table, figure and patients listing are provided in a 
separate document “Mock Tables, Listings and Figures”. 
3.1 
Objectives and endpoints 
Trial objectives and endpoints are listed in Table 3-1. 
 
Table 3-1: Objectives and endpoints of the clinical trial 
OBJECTIVES 
ENDPOINTS 
PRIMARY OBJECTIVE 
PRIMARY ENDPOINTS 
• 
(Part 1 and Part 2) Assess 
safety and tolerability 
profile of W_pro1 
monotherapy or in 
combination with 
cemiplimab 
• 
Occurrence of dose-limiting toxicities 
(DLTs). 
• 
Occurrence of treatment-emergent adverse 
events (TEAEs) reported by relationship, 
grade, and seriousness according to NCI 
CTCAE v5.0. 


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OBJECTIVES 
ENDPOINTS 
• 
(Part 2 Arms 1a and 1b) 
Evaluate preliminary anti-
tumor activity of W_pro1 
monotherapy and in 
combination with 
cemiplimab in patients 
with mCRPC based on 
ORR 
• 
Objective response rate (ORR), defined as 
the number of patients with a complete 
response (CR) or partial response (PR) per 
Prostate Cancer Working Group 3 
(PCWG3) [3] as determined by the 
investigator as best objective response 
divided by the number of patients in the 
analysis set. 
SECONDARY OBJECTIVES 
SECONDARY ENDPOINTS 
• 
Evaluate anti-tumor 
activity based on levels of 
prostate-specific antigen 
(PSA) 
• 
Prostate-specific antigen (PSA) decline of 0 
to 25%, >25% to 50%, and >50% compared 
to baseline. 
• 
PSA doubling time (PSADT) post-treatment 
on C4D1 and D1 of every fourth 
subsequent cycle (e.g., Cycle 8 Day 1 
[C8D1], C12D1, etc.) in Part 1 and Part 2 
Arms 1A and 1B, or on C4D1, C8D1, and 
end of treatment (EoT) in Part 2 Arms 2 and 
3 compared to baseline. 
• 
PSA decline of ≥50% (according to the 
PCWG3). 
• 
(Part 1) Evaluate 
preliminary anti-tumor 
activity of W_pro1 
monotherapy in patients 
with mCRPC based on 
ORR 
• 
ORR, defined as the number of patients 
with a CR or PR per PCWG3 as determined 
by the investigator as best objective 
response divided by the number of patients 
in the analysis set. 
• 
Evaluate preliminary anti-
tumor activity of W_pro1 
monotherapy or in 
combination with 
cemiplimab in patients 
with newly diagnosed LPC 
 
• 
Tumor response post-treatment compared 
to baseline. 
EXPLORATORY 
OBJECTIVES 
EXPLORATORY ENDPOINTS 
• 
Determine systemic 
induction/expansion of 
W_pro1 antigen-specific 
T cells for W_pro1 
monotherapy or in 
• 
Occurrence of de novo induction or 
increase of W_pro1 antigen-specific T cells 
in peripheral blood under treatment on 
C3D15, and/or C8D15, EoT, or safety 
follow-up compared to baseline. 


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OBJECTIVES 
ENDPOINTS 
combination with 
cemiplimab  
• 
Evaluate preliminary anti-
tumor activity of W_pro1 
monotherapy and in 
combination with 
cemiplimab in patients 
with mCRPC 
• 
Duration of response (DoR), defined as the 
time from the first occurrence of a 
documented objective response (OR) to the 
time of the first disease progression per 
PCWG3 [3], as determined by the 
investigator, or death from any cause, 
whichever occurs first. 
• 
ORR and DoR, defined as above, using 
immune-modified Response Evaluation 
Criteria in Solid Tumors (iRECIST) [4].  
• 
Progression-free survival (PFS), defined as 
the time from the first trial treatment to the 
first disease progression per PCWG3 as 
determined by the investigator, and per 
iRECIST determined by central reading, or 
death from any cause, whichever occurs 
first. 
• 
Overall survival (OS), defined as the time 
from first trial treatment until death from any 
cause. 
• 
Number of cycles received and relative 
dose intensity (RDI). 
• 
Evaluate preliminary anti-
tumor activity of 
cemiplimab in patients 
with mCRPC who have 
been previously treated 
with, and who have 
progressed after W_pro1 
monotherapy. 
• 
ORR, defined as the number of patients 
with a CR or PR per PCWG3 as determined 
by the investigator as best objective 
response (OR) divided by the number of 
patients in the analysis set. 
• 
DoR, defined as the time from the first 
occurrence of a documented OR to the time 
of the first disease progression per 
PCWG3, as determined by the investigator, 
or death from any cause, whichever occurs 
first. 
• 
ORR and DoR, defined as above, using 
iRECIST. 
• 
PFS, defined as the time from the first 
cemiplimab treatment to the first disease 
progression per PCWG3 as determined by 
the investigator, and per iRECIST 


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OBJECTIVES 
ENDPOINTS 
determined by central reading, or death 
from any cause, whichever occurs first. 
• 
PFS2, defined as the time from the first trial 
treatment to the first disease progression 
after start of cemiplimab per PCWG3 as 
determined by the investigator, or death 
from any cause, whichever occurs first. 
• 
OS, defined as the time from first trial 
treatment until death from any cause. 
• 
Number of cycles received and RDI. 
• 
Assess safety and 
tolerability profile of 
cemiplimab monotherapy 
in patients following 
progression after W_pro1 
monotherapy. 
• 
Occurrence of TEAEs reported by 
relationship, grade, and seriousness 
according to NCI CTCAE v5.0. 
• 
Evaluate preliminary anti-
tumor activity of W_pro1 
monotherapy or in 
combination with 
cemiplimab in patients 
with newly diagnosed LPC 
• 
PFS, defined as the time from the first trial 
treatment to the first disease progression 
per PCWG3 [3] as determined by the 
investigator, or death from any cause, 
whichever occurs first. 
• 
OS, defined as the time from first trial 
treatment until death from any cause. 
• 
Preliminary assessment of 
biomarkers that might act 
as potential predictive, 
pharmacodynamics, anti-
tumor, and safety 
indicators of activity of 
W_pro1 monotherapy or in 
combination with 
cemiplimab  
• 
Status of tumor mutational burden and 
immune-related gene expression (at the 
RNA level) in tumor tissue prior to 
treatment. 
• 
Change in protein expression pattern/levels 
of tumor microenvironment markers (e.g., 
CD3, CD8, MHC-I, PD-L1, etc.) and 
prostate tumor markers (e.g., PSA, PSAP, 
NKX3-1, etc.) in tumor tissue post-
treatment compared to baseline. 
• 
Baseline status or change in RNA target 
expression of W_pro1–encoded antigens in 
the post-treatment tissue compared to 
baseline.  
• 
Change in T cell clonality/diversity post-
treatment compared to baseline. 


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OBJECTIVES 
ENDPOINTS 
• 
Changes in blood biomarkers prior to and 
during trial treatment. 
Abbreviations: C = Cycle; CR = complete response; CTCAE v5.0 = Common Terminology Criteria for 
Adverse Events, version 5.0; D = Day of cycle; DLT = dose-limiting toxicity; DoR = duration of 
response; EoT = End of Treatment; iRECIST = immune-modified Response Evaluation Criteria in 
Solid Tumors; MHC = major histocompatibility complex; NCI = National Cancer Institute; NKX3-1 = 
NK3 homeobox 1; OR = objective response; ORR = objective response rate; OS = overall survival; 
PCWG3 = Prostate Cancer Working Group 3; PD-L1 = programmed cell death 1 ligand 1; PFS = 
progression-free survival; PR = partial response; PSA = prostate-specific antigen; PSADT = prostate 
specific antigen doubling time; PSAP = prostate specific acid phosphatase; RDI = relative dose 
intensity; RNA = ribonucleic acid; TEAE = treatment-emergent adverse event. 
 
 
 


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3.2 
Trial design 
Trial design 
This is an open-label, multicenter, dose titration and expansion 
four-arm trial to evaluate the safety, tolerability, 
immunogenicity, and preliminary efficacy of W_pro1 
monotherapy or in combination with cemiplimab in patients with 
mCRPC (mCRPC: Part 1 and Part 2 Arms 1A and 1B) and in 
patients with LPC eligible for treatment with ADT followed by 
radical prostatectomy (LPC: Part 2 Arms 2 and 3). 
 
The trial consists of 2 parts: Part 1 (dose titration) and Part 2 
(dose expansion). Part 2 consists of 4 arms: Arms 1A and 1B 
(mCRPC patients) and Arms 2 and 3 (LPC patients). 
Part 1 contains a dose titration for initial safety assessment and 
identification of the recommended expansion dose range 
(REDR). It will enroll mCRPC patients to receive W_pro1 
monotherapy at 3 predefined dose levels (DLs) until a 
discontinuation-of-treatment criterion is met (see Section 7 of 
the protocol). Part 1 of the trial will employ a modified 3+3+3 
design (adapted from Hamberg et al. 2010 [1]) with up to 9 
evaluable patients. 
Once the REDR is defined, the trial will commence with Part 2 
and enroll approximately 106 patients in 4 arms (see the 
expansion part, Section 4.2 of the protocol). Part 2 Arms 1A 
and 1B will enroll patients with mCRPC to receive W_pro1 
monotherapy or W_pro1 in combination with cemiplimab, and 
Part 2 Arms 2 and 3 will enroll patients with newly diagnosed 
LPC eligible for treatment with ADT (e.g., goserelin acetate) to 
receive W_pro1 monotherapy or W_pro1 in combination with 
cemiplimab. 
 
 
 


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Figure 3-1: Trial Design 
 
 
Abbreviations and Footnotes: 
C = Cycle; IV = intravenous; LPC = localized prostate cancer; mCRPC = metastatic castration-resistant prostate cancer; 
Q3W = every 3 weeks; REDR = recommended expansion dose range. 
* In combination with ADT (e.g., Goserelin). 
% Following progression after W_pro1 monotherapy, patients in Arm 1b have the option to be treated with cemiplimab 
monotherapy
mg IV Q3W. 
 
Trial population 
Part 1 (mCRPC) 
Dose titration for initial safety assessment and identification of 
the REDR. In this part patients with histologically confirmed 
mCRPC who progressed after at least 2 but no more than 3 
lines of life-prolonging systemic therapy (e.g., abiraterone or 
enzalutamide, docetaxel, cabazitaxel) or who cannot tolerate or 
have refused any of these therapies will be enrolled. Patients in 
Part 1 will receive W_pro1 monotherapy at 3 predefined dose 
levels (DLs) until a discontinuation-of-treatment criterion is met 
(see Section 7 of the protocol). Up to 9 evaluable patients will 
be enrolled in Part 1. 
 
Part 2 Arms 1A and 1B (mCRPC) 
Approximately 66 (33 per arm) patients with histologically 
confirmed mCRPC who progressed after at least 2 but no more 
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than 3 lines of life-prolonging systemic therapy (e.g., abiraterone 
or enzalutamide, docetaxel, cabazitaxel) or who cannot tolerate 
or have refused any of these therapies will be enrolled in Part 2 
Arms 1A and 1B. 
Following progression after W_pro1 monotherapy, patients in 
Arm 1B will have the option to be treated with cemiplimab 
monotherapy. 
 
Part 2 Arm 2 and Arm 3 (LPC) 
Treatment-naive patients with LPC (i.e., N0, M0) defined 
according to European Association of Urology Guidelines on 
Prostate Cancer (2018) [2] and in line with the U.S. National 
Comprehensive Cancer Network (NCCN 2020) [7], who are 
eligible for treatment with ADT (e.g., goserelin acetate) followed 
by radical prostatectomy will be enrolled in Part 2 Arms 2 and 3. 
 
A list of all inclusion and exclusion criteria can be found in 
Section 5 of the protocol.  
Trial centers and 
geographic regions 
Approximately 30 investigational sites in up to 5 countries 
including US, UK, Hungary and Germany. 
Investigational medicinal products (IMPs): 
IMP 1: 
W_pro1  
Composition: 
The W_pro1 consists of messenger ribonucleic acid (mRNA [or 
RNA]) targeting 5 antigens expressed in de novo and metastatic 
prostate cancer that are separately complexed with liposomes 
to form serum-stable RNA lipoplexes. 
Administration: 
Five slow intravenous (IV) bolus injections per administration 
(i.e., one injection per each antigen followed by a saline flush 
and separated from the next injection by at least 5 minutes) 
Dosage regimen: 
One cycle (C) is defined as 21 days. 
The patients will receive the following treatments in the 
following dose and schedule:  
 
Part 1 and Part 2 Arms 1A and 1B (mCRPC) 
• IV administration of W_pro1 on Day (D)1/8/15 of C1 
(intra-patient dose titration) and C2, thereafter starting 
with D1 of C3 every 3 weeks (Q3W) until end of treatment 
criterion is met. 
• Part 1/Dose Titration 


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- 
Three doses of W_pro1 will be used for an intra-
patient dose titration during C1:
µg, 
 µg, and 
 µg of total RNA, comprising
 µg, 
µg, and 
 µg of RNA of each of the 5 antigens encoded by 
the W_pro1, respectively. 
• Part 2/Expansion 
- 
REDR was selected after the review of individual 
and cumulative safety data, and preliminary 
pharmacodynamic data of Part 1 by the Safety 
Review Committee (SRC). The selected dose 
range consists of a starting first dose of W_pro1 of 
µg, with an intra-patient dose titration to 
µg in 
the second dose, and 
 µg of total RNA in the 
next doses. Total RNA of 
µg, 
 µg and 
 µg 
comprise
µg, 
µg, and 
µg of RNA of each of 
the 5 antigens encoded by the W_pro1, 
respectively. 
- 
Part 2 Arm 1A: Cemiplimab 
mg IV Q3W. 
- 
Part 2 Arm 1B: Following progression after W_pro1 
monotherapy, patients have the option to be treated 
with cemiplimab
mg IV Q3W monotherapy. 
Part 2 Arms 2 and 3 (LPC) – Part 2/Expansion ONLY 
• IV administration of W_pro1 on D1/8/15 of C1 (intra-
patient dose titration) and C2, thereafter starting with D1 
of C3 in a Q3W schedule until C8 followed by radical 
prostatectomy. 
• Part 2 Arm 2: Cemiplimab
mg IV Q3W. 
Duration of 
treatment: 
• Part 1 and Part 2 Arms 1A and 1B (mCRPC): The 
treatment with W_pro1 will last until unacceptable toxicity 
or disease progression. 
• Part 2 Arms 2 and 3 (LPC): The treatment with W_pro1, 
cemiplimab will last until unacceptable toxicity or disease 
progression, or up to C8.  
• If either W_pro1 or cemiplimab needs to be discontinued, 
treatment with either cemiplimab or W_pro1 can continue 
upon investigator’s and sponsor’s agreement.  
• If treatment with ADT (e.g., goserelin acetate) needs to be 
discontinued, cemiplimab and/or W_pro1 also need(s) to 
be discontinued. 
 
CCI
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IMP 2: 
Cemiplimab (LIBTAYO) 
Composition: 
Programmed death receptor-1 (PD-1) blocking antibody 
Dosage regimen and 
duration of treatment: 
Refer to above description of IMP1 for dosage regimen and 
duration of treatment 
Non-investigational medicinal product (NIMP):  
Part 2 Arms 2 and 3 (LPC) 
ADT, e.g., Goserelin acetate subcutaneous (SC) injection at a dose of 10.8 mg every 
12 weeks (Q12W) or other ADT according the current prescribing information valid in a 
given country. 
Product: 
Goserelin acetate (Zoladex® LA 10.8 mg implant) 
Composition: 
Goserelin acetate (equivalent to 10.8 mg goserelin) 
Administration: 
SC 
Dosage regimen: 
One 10.8 mg depot injection given into the anterior abdominal 
wall Q12W 
Duration of 
treatment: 
Two injections (≤7 days C1D1 and 12 weeks after the first 
injection); treatment will last until unacceptable toxicity or 
disease progression, or up to C8 
Treatment and trial 
duration 
Treatment and follow–up duration: 
Part 1 and Part 2 Arms 1A and 1B (mCRPC): 
mCRPC patients will be treated until a discontinuation-of-
treatment criterion is met. One cycle is defined as 21 days. End 
of treatment (EoT) assessment will be performed up to 21 days 
after administration of last dose of IMP for patients who 
discontinued trial treatment, except if patient was lost to follow-
up or died. 
All patients (Part 1 and Part 2 Arms 1A and 1B) will be actively 
followed up 30 days for safety (D30 Safety FU) after last intake 
of W_pro1. Patients in Part 2 Arm 1A will be followed up 90 days 
for safety (D90 Safety FU) after last intake of cemiplimab, or 30 
days for safety (D30 Safety FU) after last intake of W_pro1, 
whichever is later. All patients will be followed up 6 and 12 
months after last IMP administration for efficacy.  
Within 28 days after confirmation of disease progression, 
patients of Arm 1B can optionally start cemiplimab monotherapy 
and will follow the Schedule of Activities (SoA) shown in Section 
13.6 after performing the EoT for W_pro1 treatment.  
Part 2 Arm 2 and Arm 3 (LPC): 


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LPC patients will be treated with up to 8 cycles or until 
unacceptable toxicity or disease progression. One cycle is 
defined as 21 days. EoT assessment will be performed up to 21 
days after administration of last dose of IMP for patients who 
discontinued trial treatment, except if patient was lost to follow-
up or died.  
After EoT assessment a Safety follow-up (FU) after 30 days for 
Arm 2 and Arm 3 and an additional Safety FU after 90 days for 
Arm 2 patients are performed. Both Arms 2 and 3 will be 
followed up 6 and 12 months after last IMP administration for 
efficacy. 
Trial duration: 
First patient was included on 19 December 2019. 
The end of the trial is defined as the date of last patient contact, 
whether in-person or by phone, for the last patient in the trial 
globally, including the efficacy follow-up for 12 months after the 
last dose of trial treatment. 
Planned number of 
patients 
There will be 3 to 9 patients in Part 1 (dose titration part, single 
arm) and up to 106 patients in Part 2 (expansion part, 4 arms: 
up to 33 patients in Arm 1A and Arm 1B, respectively, and 
approximately 20 patients in Arm 2 and Arm 3, respectively). 
Drop-outs may be replaced. In total, there will be approximately 
115 patients. 
Re-screening of patients is allowed. 
Randomization and 
blinding 
At screening, patients will be assigned a unique number (patient 
identification code), regardless of whether they actually receive 
trial treatment.  
In Part 2, patients with mCRPC treated in Arm 1A or Arm 1B, 
and patients with LPC treated in Arm 2 or Arm 3, will be 
randomized in 1:1 ratio. Central randomization will be used. No 
stratification factors will be used for the randomization. 
The site will contact the central randomization service prior to 
the start of trial treatment administration for each patient. The 
treatment assignment will be recorded on the applicable 
electronic case report form (eCRF), as required. This is an 
open-label trial. 
Tumor assessment 
schedule 
Part 1 and Part 2 Arms 1A and 1B (mCRPC): 
Bone scintigraphy (bone scans) and CT/MRI of the chest, 
abdomen, and pelvis should be performed at the following time 
points:  
- 
during screening period (within 28 days before C1D1)  
- 
at C3D15 (±7 days)  


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- 
every 8 weeks (±7 days) for 24 weeks (i.e. between 
C6D1 and C8D15) 
- 
and every 3 months (±7 days) thereafter, i.e., from 
C11D15 until disease progression is assessed by the 
investigator or the start of a new anti-cancer therapy or 
withdrawal of consent, or death, whichever occurs first 
- 
At EoT visit (only if clinically indicated); not required if 
previous imaging was performed within ≤ 9 weeks before 
the EoT visit 
Patients in Arm 1B who moved to treatment with cemiplimab 
monotherapy following progression after W_pro1 monotherapy, 
should have radiographic assessments performed every 3 
months (±7 days) thereafter, until disease progression is 
assessed by the investigator or the start of new anti-cancer 
therapy or withdrawal of consent, or death, whichever occurs 
first. 
 
Part 2 Arms 2 and 3 (LPC): 
Tumor measurement using multi-parametric MRI (mpMRI) or 
MRI will be used consistently throughout the trial. The same 
imaging modality should be used at screening and at all 
subsequent assessments. Tumor measurements should be 
performed at the following time points: 
- 
during screening period (within 28 days before C1D1) 
- 
prior to surgery (i.e. at the end of C8/EoT visit) 


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Treatment 
overview: 
 
 
Treatment sequence: (if applicable) NIMP ADT is to be administered first, thereafter 
W_pro1, and then cemiplimab. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations and Footnotes: 
LPC = localized prostate cancer; mCRPC = metastatic castration resistant prostate cancer; Q3W = every 
three weeks. 
& 
Recommended dose range (REDR) is confirmed in Part 1. 
* 
Maximum administered dose 
µg; minimum administered dose 
µg; no dose re-escalation allowed. 
# 
In combination with ADT (e.g., Goserelin). 
$ 
From Day 1 of C1 onward, each patient will receive the individual standard dose (or the highest tolerated 
dose from Cycle 1) at each W_pro1 administration. 
% 
Following progression after W_pro1 monotherapy, patients in Arm 1b will have the option to be treated 
with cemiplimab monotherapy
 mg IV Q3W. 
 
 
Day
1
8
15
1
8
15
1
8
15
µg IV
X
µg IV
X
µg IV
X
X
X
X
X
→
Q3W
mg IV
Q3W
X
X
X
→
Q3W
W_pro1$
Cemiplimab
Part 2
Arm 1a (W_pro1 + cemiplimab in mCRPC)
Arm 2# (W_pro1 + cemiplimab in LPC)
C1
C2
C3 →
Day
1
8
15
1
8
15
1
8
15
µg IV
X
µg IV
X
µg IV
X
Highest 
tolerable dose*
X
X
X
X
→
Q3W
W_pro1$
C1
C2
C3 →
Part 1
Dose Titration&
Day
1
8
15
1
8
15
1
8
15
µg IV
X
µg IV
X
µg IV
X
X
X
X
X
→
Q3W
W_pro1$
C2
C3 →
Part 2
Arm 1b% (W_pro1 monotherapy in mCRPC)
Arm 3# (W_pro1 monotherapy in LPC)
C1
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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3.3 
Schedule of activities 
See Section 13.6 for the SoA. 
4 
STATISTICAL HYPOTHESES 
For each arms of Part 2, Arm 1A and 1B, the null hypothesis that the true response rate is 
5% will be tested against a one-sided alternative (i.e. H0: ORR = 5% vs H1: ORR>5%). 
There will be no formal comparison between treatment groups. No further statistical 
hypothesis is under test. 
Apart from this hypothesis, no formal statistical comparison between treatment groups will 
be performed for any of the other endpoints. All other p-values will be considered as 
supportive or explorative. The results of all other endpoints will be described with nominal 
p-values without any statement on statistical significance. 
5 
INTERIM ANALYSES AND ANALYSIS SEQUENCE 
The interim analysis was performed based on all available data from the clinical data cut-
off that will occur when the required number of patients in the respective arm had 
performed the first post-baseline tumor assessment or had been diagnosed with 
unequivocal clinical progression. 
The final analysis of the trial will be performed based on all available data from a clinical 
data cut-off that will occur after patients in the respective setting of Part 2 (Arms 1A, 1B, 
and 2, 3) have completed 8 cycles of treatment or discontinued.  
However, after the interim analysis, the enrollment of Part 2 Arms 1A and 1B (mCRPC) 
was stopped prior to the complete enrollment of the planned LPC patients. Therefore, the 
final analysis for mCRPC and the final analysis for LPC are planned to be performed 
separately.  
The final analysis for mCRPC will be performed based on all available data from a clinical 
data cut-off that will occur after all the enrolled patients in Part 2 Arms 1A and 1B 
(mCRPC) have completed 8 cycles of treatment or discontinued.  
The final analysis for patients with LPC will be performed based on all available data  from 
a clinical data cut-off that will occur after all the planned patients in the Part 2 Arms 2 and 
3 (LPC) have completed 8 cycles of treatment or discontinued. 
 
Note: for both final analyses, the data from both LPC and mCRPC will be analyzed.  
• 
At the final analysis for mCRPC, all the data for LPC up to the data cutoff for this 
analysis will also be analyzed. 
• 
At the final analysis for LPC, all the data for mCRPC up to the data cutoff for this 
analysis will also be analyzed. 
 


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A further analysis, termed Follow-up analysis, will be performed when the last patient 
discontinues from the trial. For the Follow-up analysis only a subset of TFLs generated for 
the main analysis may be produced again, this analysis will include all new data collected 
in the database. All TFLs to be generated for the Follow-up analysis will be defined after 
the final analysis has be performed.  
An Independent Data Monitoring Committee is not planned for this trial.  
The patient’s safety will be monitored throughout the trial by the SRC. The SRC will be 
chaired by the sponsor’s Medical Monitor and membership will include at a minimum the 
trial principal investigators, members of the sponsor medical and safety departments, as 
well as additional staff as appropriate.  
The SRC will review all DLTs and suspected unexpected serious adverse reactions, make 
the REDR recommendation at the end of the Dose Titration Part (Part 1) and periodically 
review safety and efficacy in Part 2. The SRC will make a recommendation to the sponsor 
after each meeting and how to proceed with the trial and whether to activate the respective 
expansion arms of the trial. The SCR will meet at least every 3 months throughout the trial.  
The materials provided for review to the SRC, the SRC role and responsibilities and the 
general procedures (including communications) are defined and documented in the SRC 
charter (v4.0, dated 02 NOV 2020). The preparation of the review material for the SRC is 
not part of the SAP for this trial.  
6 
SAMPLE SIZE DETERMINATION 
The sample size for Part 1 is driven by the 3+3+3 trial design and will range from 3 to 9 
DLT evaluable patients depending on the number of DLTs which may occur. The main 
objective for the Part 2 is to perform exploratory biomarker analyses in the LPC setting and 
to preliminary assess the efficacy in terms of response in the mCRPC setting.  
Simon's two-stage design [5] based on the Minimax approach will be used for Part 2 
Arm 1A and 1B separately. The null hypothesis that the true response rate is 5% will be 
tested against a one-sided alternative. In the first stage, 20 evaluable patients will be 
treated. Enrollment will continue following the sponsor’s decision (upon recommendation 
from the SRC’s review) and 13 evaluable patients may be treated for a total of 33 
evaluable patients. If there are 1 or fewer responses in the first 20 evaluable patients, the 
enrollment for that arm may be stopped. The null hypothesis will be rejected if 5 or more 
responses are observed in 33 evaluable patients. This design yields a type I error rate of 
2.5% and power of 80% when the true response rate is 20%. 
A patient will be considered as evaluable if included in the primary analysis set (mITT set, 
see Section 7.1) which is defined as all patients who are randomized to the IMP and have 
a baseline and at least one post-baseline (i.e., one on-treatment or post-treatment) tumor 
assessment (clinical or imaging assessment). 
No formal sample size calculation is performed for the LPC setting in Part 2 (Arms 2 and 
3) due to its exploratory nature. However, 20 patients are planned to be enrolled into 
Arm 2 and Arm 3. Based on this sample size (N=20) the one-sided 95% CI of binary 


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endpoints will have a width of up to +/-0.19 in each group depending on the observed 
effect size. 
7 
ANALYSIS SETS AND SUBGROUPS 
7.1 
Analysis sets 
The following analysis sets are defined: 
Population 
Description 
Screened  
The screened analysis set is defined as all patients who sign the 
informed consent form (ICF). 
Intent-to-Treat (ITT) 
Part 1: The ITT set is defined as all patients to whom IMP is assigned. 
Part 2: The ITT set is defined as all patients who are randomized to the 
IMP. 
Modified Intent-to-Treat 
(mITT) 
Part 1: The mITT set is defined as all patients to whom IMP is assigned 
and have a baseline and at least one post-baseline (i.e., one on-
treatment or post-treatment) tumor assessment (clinical or imaging 
assessment). 
Part 2: The mITT set is defined as all patients who are randomized to the 
IMP and have a baseline and at least one post-baseline (i.e., one on-
treatment or post-treatment) tumor assessment (clinical or imaging 
assessment). 
Safety (SAF) 
The safety set is defined as all patients who have received IMP (i.e., at 
least 1 dose of W_pro1 and/or cemiplimab). 
DLT Evaluation  
Only applicable for Part 1:  
The DLT evaluation set includes all patients from the safety set who 
either have completed the DLT evaluation period and meet the minimum 
exposure criterion or have experienced a DLT during C1.  
Patients who do not experience any DLTs during C1 are considered to be 
evaluable if they have been observed for a minimum of 21 days following 
the first dose and are considered to have sufficient safety data to 
conclude that a DLT did not occur. A patient is considered to have met 
the minimum exposure criterion if the relative dose intensity of W_pro1 in 
C1 is at least 90%.  
Per Protocol (PP) 
The per protocol (PP) set is defined as all patients who have received 
IMP and fulfil the following criteria: 
• The absence of any important protocol deviations that could affect the 
primary efficacy analysis 
• The completion of a minimal exposure to the treatment of 1 cycle 
• Availability of baseline and at least one on-treatment / post-treatment 
tumor assessment 
Important deviations will lead to an exclusion of patients from the PP set 
and will be agreed at the data review meeting (DRM) prior to database 
snapshot for the final analysis. Protocol deviations that may be 
considered important will be specified in the SAP (see Section 7.2) 
Pharmacodynamic 
The pharmacodynamic set is defined as all patients who have received 
IMP (i.e., at least 1 dose of W_pro1 and/or cemiplimab) and with a 
baseline and at least 1 on-treatment/post-treatment follow-up 


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Population 
Description 
pharmacodynamic assessment as specified in Section 8.8.1 (i.e. 
Hormones (Testosterone), Cytokines).  
Subsequent Cemiplimab 
Monotherapy on Progression 
(Cemi Mono on PD) 
Only applicable for Part 2 Arm 1B:  
The subsequent cemiplimab monotherapy on progression set (Cemi 
Mono on PD) is defined as all mCRPC patients in Arm 1B (W_pro1 
monotherapy) who switch to cemiplimab monotherapy after disease 
progression and who received at least one dose of cemiplimab. 
 
The DLT evaluation set will be used for the evaluation of DLTs in order to assess the 
REDR in Part 1 of the trial.  
The safety set will be used for all other safety analyses, while the mITT set will be used as 
primary analysis set for efficacy analyses.  
The subsequent cemiplimab monotherapy on progression set will be used for all 
exploratory safety and efficacy analyses for the Arm 1B patients who received cemiplimab 
(i.e., at least 1 dose of cemiplimab) after progression to W_pro1 monotherapy. 
The ITT analysis set will be used for disposition analyses. 
Further, the ITT and PP sets will be used for sensitivity analyses of some predefined 
efficacy endpoints depending on the number of patients excluded. If none of the patients 
are excluded from the mITT set, compared to the ITT set, or if the number of patients 
excluded from the PP set is small (exclusion rate ≤10%), no additional sensitivity analyses 
for the ITT or the PP set will be generated. The final decision to perform sensitivity 
analyses for the ITT set or for the PP set will be made during the DRM meeting for the final 
analysis. 
All safety analyses and analyses based on the Pharmacodynamic set will be based on the 
treatment actually taken by the patient (“as treated”).  
All other analyses will be based on the treatment the patient was assigned/randomized to 
(“as randomized”), unless stated otherwise. 
7.2 
Protocol deviations 
Protocol deviation management for this trial is detailed in the trial specific Protocol 
Deviation and Non-compliance Management Plan. According to this plan, protocol 
deviations or site non-compliance are documented concisely in the Clinical Trail 
Management System (CTMS) and periodically reviewed as part of the project oversight by 
a wider study team. 
Protocol deviations are failures to adhere to the inclusion/exclusion criteria and protocol 
requirements and will be classified into important protocol deviations and not important 
protocol deviations. 
• 
Important protocol deviations are a subset of protocol deviations that may significantly 
affect the completeness, accuracy, and/or reliability of the trial data or that may 
significantly affect a patient’s rights, safety, or well-being. For example, important 


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protocol deviations may include enrolling patients in violation of key eligibility criteria 
designed to ensure a specific patient population or failing to collect data necessary to 
interpret primary endpoints, as this may comprise the scientific value of the trial 
• 
Non-important protocol deviations are those that are not considered to significantly 
affect the efficacy evaluation and hence do not warrant patients’ exclusion from the PP 
set 
• 
Important protocol deviations will be identified by study team review during the DRM 
prior to database snapshot for main analysis 
Additional important protocol deviations may be defined at the DRM prior to data base lock 
for the main analysis. During the DRM, protocol deviations as specified in this section of 
the SAP and all protocol deviations as reported in the CTMS system will be evaluated and 
decided which important protocol deviation will results in an exclusion of a patient from the 
PP set. 
Important and non-important protocol deviations will be presented in a listing. The number 
and percentage of patients excluded from the PP set will be summarized in total and by 
protocol deviation type for the ITT set. 
7.2.1 
Protocol deviations due to COVID-19 
Protocol deviations related to COVID-19 are documented in the CTMS with the preface 
“COVID-19” in the deviation description. 
COVID-19 related protocol deviations are, for example: 
• 
COVID-19, Visit xx on date xx of patient not conducted due to site facility re-
organization related to COVID-19 disruption  
• 
COVID-19, missing Visit xx due to patient affected by COVID-19 
A separate table will be generated summarizing the number and percentage of patients with 
a COVID-19 protocol deviation. Respective data will be listed. 
Protocol deviation due to COVID-19 will be summarized using the ITT set. 
7.3 
Subgroups 
The following subgroups are defined for statistical analysis: 
• 
Age categories (< 50 years, >= 50 - < 65 years , >= 65 years) 
• 
mCRPC patients: Visceral metastasis at study entry (Yes, No) 
• 
mCRPC patients: Prior treatment with Docetaxel or other Taxanes (Yes, No) 
(use ATC Level 4 Code = L01CD for the derivation) 
 
• 
LPC patients: PSA level at baseline  
(<= 20 ng/mL, > 20 ng/mL) 
• 
LPC patients: NCCN Risk Group at diagnosis 
(Very low risk, Low risk, Intermediate risk, High risk, Very high risk, Unkown) 


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The definition of subgroups and the respective cut points could be modified for the 
analysis depending on the enrolled patients. Further subgroups may be defined during the 
DRM meeting for the final analysis. 
Subgroup analyses will be provided for the mITT set (for ORR and PFS per PCWG3), 
unless otherwise specified. 
8 
STATISTICAL ANALYSES 
8.1 
General considerations 
In general, the statistical analysis will be performed by trial part (i.e., Part 1 and Part 2) and 
by treatment group in the Part 2 (i.e., Part 1 mCRPC W_pro1, Part 2 mCRPC W_pro1 + 
Cemiplimab, Part 2 mCRPC W_pro1, Part 2 LPC W_pro1 + Cemiplimab, Part 2 LPC 
W_pro1). A detailed description of treatment labels to be used for the analysis is provided 
in Section 13.4. 
For Part 2 of the trial all analyses (disposition, baseline characteristics, efficacy and safety 
(except adverse event (AE) analysis)) will be analyzed by treatment group and in addition 
for 3 combined treatment groups “Part 2 Total mCRPC”, “Part 2 Total LPC” and “Part 2 
Total”. “Part 2 Total” is an optional treatment group only for some predefined tables.  
AE analyses will be analyzed for 6 additional combined treatment groups i.e. “Part 2 Total 
Monotherapy”, “Part 2 Total Combination Therapy”, “Part 2 Total”, “Parts 1 and 2 Total 
mCRPC”, “Parts 1 and 2 Total Monotherapy” and “Parts 1 and 2 Total”. A detailed 
description of all combined treatment groups is available in Section 13.4. 
Continuous variables will be summarized by treatment group using the following 
descriptive statistics: number of patients with non-missing data (n), mean, standard 
deviation, median, minimum, maximum, lower quartile (Q1) and upper quartile (Q3) where 
appropriate. 
Categorical variables will be summarized by treatment group presenting absolute and 
relative frequencies (n and %) of patients in each category.  
Shift tables from baseline will summarize only cases, where both time points are available, 
to avoid a “missing” category. The percentages are calculated with respect to the available 
patients. 
Generally, only measurements at scheduled visits will be summarized and included in the 
tables by visit. Unscheduled measurements will be included in the listings, only.  
Time-to-event-endpoints (DoR, PFS, and OS) will be analyzed using Kaplan-Meier 
methodology and censored in accordance with the US FDA Guidance: “Clinical Trial 
Endpoints for the Approval of Cancer Drugs and Biologics” [6]. 
The median survival time (including two-sided 95% confidence limits according to 
Brookmeyer and Crowley) and the first and third quartiles will be presented for each 
treatment group. Survival rates (including 95% confidence interval (CI) based on 
Greenwood's formula) as well as the number and percentage of patients with events, 


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censored and under risk will be displayed for selected time points (e.g. after 3 months, 
after 6 months and after 12 months). 
The survival distributions for two treatment groups will be compared using the log-rank 
test, and the p-value will be provided. The associated hazard ratio (HR) and two-sided 
95% confidence interval will be estimated by using Cox proportional hazard model with 
treatment as model covariate.  
All treatment comparisons, except the analysis defined for the primary efficacy endpoint 
see Section 4, are purely exploratory. Exploratory treatment comparisons will be 
performed separately for patients with mCRPC (comparison of Arm 1A versus Arm 1B) 
and for patients with LPC (comparison of Arm 2 versus Arm 3). 
The time-to-event analysis will be illustrated using Kaplan-Meier plots by treatment groups. 
Efficacy data collected for patients in Arm 1B after the switch from W_pro1 monotherapy to 
cemiplimab monotherapy will not be considered in the efficacy analyses. These 
measurements will only be considered in the exploratory efficacy analyses comprising 
ORR, DoR, PFS (per PCWG3 and iRECIST (central reading)) and PFS2 on cemiplimab 
monotherapy based on last tumor assessment prior to start of cemiplimab treatment. 
These exploratory endpoints to analyze the preliminary anti-tumor activity of cemiplimab 
monotherapy will be generated using the subsequent cemiplimab monotherapy on 
progression set. More details regarding these analyses can be found in Section 8.7.4.2. 
The safety and tolerability profile of cemiplimab monotherapy will be analyzed using the 
subsequent cemiplimab monotherapy on progression set. The definition of cemiplimab 
TEAEs will be provide in detail in Section 8.9.3. All other safety data (e.g. laboratory, 
electrocardiogram (ECG), vital signs) reported for patients in Arm 1B after the switch to 
cemiplimab monotherapy will be included in the respective listings. 
All relevant data will be listed. The listing will be sorted by treatment group, patient number 
and date/time of assessment (if applicable). Unscheduled measurements will be included 
in the listings. 
See Section 11 for the definition of planned summary tables, figures and listings. Templates 
for each unique table and patient listing are provided in a separate document “Mock Tables, 
Listings and Figures”.  
8.2 
Key definitions 
Date/time of first administration of IMP (W_pro1 or Cemiplimab): 
Is defined as first administration date/time of IMP (W_pro1 or cemiplimab), whichever was 
administered first. 
Baseline Definition: 
Baseline is defined as last available value prior to or on the date/time of first administration 
of IMP (W_pro1 or cemiplimab, whichever was administered first). Unscheduled 
measurements prior to first administration of IMP will be considered in the calculation of 
the baseline values. In the case that date/time of first administration of IMP is missing (i.e., 


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for randomized not treated patients) the date/time of randomization will be used for the 
definition of baseline values. 
Cemiplimab Baseline – Baseline definition for Arm 1B patients who switch to 
cemiplimab monotherapy: 
Cemiplimab Baseline is defined as last available value prior to or on the date/time of first 
administration of cemiplimab. 
In case no time of the assessment is reported, measurements at the same date as first 
administration of cemiplimab will be considered as baseline. 
Change and percent change from baseline: 
Change from baseline will be calculated as follows:  
• 
Change from baseline = post-baseline assessment value – baseline assessment 
value. 
• 
Percent change from baseline = (post-baseline assessment value – baseline 
assessment value) / baseline assessment value * 100. 
Age (in years) at date of informed consent: 
Age is derived in the database based on the collected Year of birth as follows: 
Age = ICF Date – (01July + Year of birth ) / 365.25. 
Age as derived in the database will be used for all analyses. 
Body mass index (BMI): 
BMI will be calculated as follows:   
BMI ൬kg
m2൰= Weight (kg)
Height(m)2 
Duration: 
Duration will be calculated as follows:  
• 
Duration (days) = last observation date – first observation date + 1 
For conversion of days to months or years the following rules will be applied: 
• 
1 month = 30.4375 days 
• 
1 year = 365.25 days 
Time from first diagnosis to enrollment (in months): 
Date of initial diagnosis is collected in Month/Year. Missing day will be replaced with the first 
day of the month. In case month is not reported, missing month will be replaced with July. 
Time from first diagnosis to enrollment (months) will be calculated as: 
(ICF date – imputed date of initial diagnosis) / 30.4375  


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Time from treatment start to post treatment prostatectomy for LPC patients 
(in days): 
For date of prostatectomy or radical prostatectomy, missing day will be replaced with the 
first day of the month. In case month is not reported, missing month will be replaced with 
July. 
Time from treatment start to prostatectomy (days) will be calculated as: 
(Date of prostatectomy – date of first IMP administration (W_pro1 or cemiplimab) + 1  
Study day:  
Study day is defined as follows:  
If date of assessment is on or after the date of first IMP administration (W_pro1 or 
cemiplimab):  
• 
Date of assessment – date of first IMP administration + 1 
If date of assessment is before date of first IMP administration (W_pro1 or cemiplimab): 
• 
Date of assessment – date of first IMP administration 
Laboratory values with “< xx” or “> xx”: 
Any laboratory values given as “< xx” or “> xx” in the database will be imputed with the 
numeric value of xx without the sign for the descriptive statistics and the calculation of 
changes from baseline (e.g., a value of < 1 will be imputed as 1 for the calculations).  
Last date known to be alive: 
Last date known to be alive is defined as last documented date in the database for the 
patient, including all visit dates, assessment dates (if different from visit dates), trial 
treatment administration dates, tumor assessment dates, end of treatment dates, date of 
trial completion or early trial withdrawal date, start/stop dates of AEs, PSA response date, 
survival follow-up date (where patients survival status is alive), whichever comes last.  
Start of Follow-up Period: 
Part 1 and Part 2 mCRPC patients: Follow-up period starts at the administration of the last 
dose of IMP.  
Part 2 LPC patients: Follow-up period starts at the last administration of IMP at Cycle 8 or 
at administration of the last IMP in case of discontinuation of trial treatment. 
Pooling of centers: 
No pooling of centers is planned for this trial. 
Conventions for imputing missing/partially missing dates:  
When computations on dates are to be performed, incomplete/missing dates will be 
imputed using the following rules. 


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• 
Missing day, month/year present: If the month/year is the same as the month/year of 
the first IMP administration date, then impute missing start dates with first IMP 
administration date. Otherwise, for dates corresponding to a start date, impute with the 
first day of the month and, for dates corresponding to a stop date, impute with the last 
day of the month. 
• 
Missing month/day, year present: If the year is the same as the year of the first IMP 
administration date, then impute missing start dates with first IMP administration date. 
Otherwise, for dates corresponding to a start date, impute with the first day of the year 
and, for dates corresponding to a stop date, impute with the last day of the year. 
• 
Missing month/day/year: no imputation. 
• 
In case imputed start date is after available stop date, the imputed start date will be 
replaced with the stop date to avoid negative durations. 
This imputation method will be applied to the following dates: 
• 
Onset date of AEs (for treatment-emergent purpose), incomplete AE end dates  
• 
Medical history start date to define prior medical history and concomitant diseases 
• 
Date of prior/concomitant medication (start dates) to define prior and concomitant 
medication, incomplete stop dates of prior/concomitant medications  
Conventions for imputing missing/partial start dates of the subsequent anti-
cancer therapy: 
• 
If the start date of the first subsequent anti-cancer therapy is missing, it will be imputed 
with the date of the End of Treatment (EoT) visit.  
• 
Missing day, month/year present: If the month/year is the same as the month/year of 
the EoT visit date, then impute missing start dates with EoT visit date. Otherwise, for 
dates corresponding to a start date, impute with the first day of the month and, for 
dates corresponding to a stop date, impute with the last day of the month. 
• 
Missing month/day, year present: If the year is the same as the year of the EoT visit 
date, then impute missing start dates with the EoT visit date. Otherwise, for dates 
corresponding to a start date, impute with the first day of the year and, for dates 
corresponding to a stop date, impute with the last day of the year. 
• 
If the EoT visit date is missing, the date of the last study treatment administration + 14 
days to be used for the imputation. 
• 
In case imputed start date is after available stop date, the imputed start date will be 
replaced with the stop date to avoid negative durations. 
Clinical progression: 
Clinical progression reported more than 14 days after start of the first subsequent anti-
cancer therapy will not be considered in the analysis of clinical progression.  


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Best Overall Response (BOR) based on Radiological Soft Tissue Evaluation: 
The BOR is defined as a single best response status at any tumor response assessment 
after first administration of IMP and prior to or at the start date of the first subsequent anti-
cancer therapy. Overall response of PD within 14 days after the start date of the first 
subsequent anti-cancer therapy will be considered. 
Only responses up to and including the date of the first progressive disease will be 
considered in the derivation of the BOR. 
The following order of tumor response categories will be used, with “Complete Response” 
is the best category:  
Complete Response (CR) – Partial Response (PR) – Stable Disease (SD) – Progressive 
Disease (PD) – Not Evaluable (NE) – Not Applicable (NA).  
Best Overall Response (BOR) based on iRECIST (central reading): 
The following order of tumor response categories will be used to define the BOR category 
based on iRECIST (central reading), with “Complete Response” is the best category:  
Complete Response (iCR) – Partial Response (iPR) – Stable Disease (iSD) - Unconfirmed 
Progressive Disease (iUPD) – Confirmed Progressive Disease (iCPD) – Not Evaluable 
(NE) – Not Applicable (NA). 
Only central reading assessments after first administration of IMP and prior to or at the 
start date of the first subsequent anti-cancer therapy will be considered in the derivation. 
Overall response of iUPD or iCPD within 14 days after the start date of the first 
subsequent anti-cancer therapy will be considered. 
Only responses up to and including the date of the first progressive disease will be 
considered in the derivation of the BOR. 
Further information on the definition of the BOR based on iRECIST is available in Section 
13.3. 
PSA Response definition based on PCWG3: 
PSA response definition based on PCWG3 will be derived based on the PSA response 
data reported by the investigator. 
If a PSA PD occurred >= 12 weeks after first administration of IMP. This PSA PD needs no 
confirmation. 
For the derivation of best overall PSA Response based on PCWG3, the PSA responses 
have to be confirmed. The following rules have to be implemented for PSA response 
confirmation: 
 
• 
PSA PR Response Confirmation  
o PSA PR needs to be confirmed by: 
 
Subsequent [Radiological Soft Tissue PR or CR response] or 
Subsequent [PSA PR response] 


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 
Which occurs within >= 20 days and <= start date of first subsequent 
anti-cancer therapy, immediately after initial PSA PR response 
 
With no worse response (SD, PD) between initial PR and confirmation 
response  
 
Worse responses are defined as [Radiological Soft Tissue SD or PD 
response] or [Clinical Progression Event] or [Progressive Bone 
Disease] or [PSA SD or PD response]  
• 
PSA SD Response Confirmation  
o PSA SD needs to be confirmed by:  
 
Subsequent [Radiological Soft Tissue SD, PR or CR response] or 
Subsequent [PSA SD or PR response] 
 
Which occurs within >= 20 days and <= start date of first subsequent 
anti-cancer therapy, immediately after initial PSA SD response 
 
With no worse response (PD) between initial SD and confirmation 
response  
 
Worse responses are defined as [Radiological Soft Tissue PD 
response] or [Clinical Progression Event] or [Progressive Bone 
Disease] or [PSA PD response]  
• PSA PD Response Confirmation 
o If a PSA PD occurred < 12 weeks after first administration of IMP, this PSA 
PD needs to be confirmed by: 
 Another PSA PD that occurred immediately after the initial PSA PD 
and >= 12 weeks after first administration of IMP and <= start date of 
first subsequent anti-cancer therapy + 14, immediately after the initial 
PSA PD response. 
 Subsequent [Radiological Soft Tissue PD] or [Clinical Progression] or 
[Progressive Bone Disease] immediately after the initial PSA PD and 
<= start date of first subsequent anti-cancer therapy + 14. 
 
PSA PD confirmation can only occur if there are no better responses 
(CR, PR, SD) between the initial PSA PD and confirmation 
assessment.  
 Better responses are defined as [Radiological Soft Tissue CR, PR or 
SD response] or [PSA PR, SD response]  
Best Overall PSA Response definition based on PCWG3: 
The best overall PSA response based on PCWG3 is defined as a single best PSA 
confirmed response status at any response assessment after first administration of IMP 
and prior to or at the start date of the first subsequent anti-cancer therapy. Overall 
response of PD within 14 days after the start of the first subsequent anti-cancer therapy 
will be considered. 
Only responses up to and including the date of the first progressive disease will be 
considered in the derivation of the best overall PSA Response. 


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The following order of response categories will be used, with “Partial Response” is the best 
category:  
Partial Response (PR) – Stable Disease (SD) – Progressive Disease (PD) – Unknown – 
Not Applicable (NA).  
 
Best Overall Response (BOR) based on PCWG3: 
The rules for the definition of BOR based on PCWG3 are referring to the following data 
reported in the CRF: 
• 
Confirmed PSA response reported by the investigator (see Section 8.2 for more details 
regarding PSA response confirmation) 
• 
Radiological Soft Tissue Evaluation (response data collected in the CRF on the 
“RECIST 1.1” page) 
• 
Clinical Progression (data collected in the CRF on the “Clinical Progression” page) 
• 
Bone Disease Progression (data collected in the CRF on the “Bone Lesion” pages with 
Clinical Impression = Progression) 
 
Only assessments after first administration of IMP and prior to or at the start date of the 
first subsequent anti-cancer therapy will be considered in the derivation. Overall response 
of PD within 14 days after start date of the first subsequent anti-cancer therapy will be 
considered. 
Only responses up to and including the date of the first progressive disease will be 
considered in the derivation of the BOR.  
Overall Response of CR, PR, SD per PCWG3 is based on radiological soft tissue 
response or confirmed PSA response. 
Progression of Disease per PCWG3 is based on the earliest radiological soft tissue 
progression, Bone disease progression, confirmed PSA progression or clinical 
progression. 
The following order of tumor response categories will be used, with “Complete Response” 
is the best category:  
Complete Response (CR) – Partial Response (PR) – Stable Disease (SD) – Progressive 
Disease (PD) – Not Evaluable (NE) – Not Applicable (NA).  
 
Derivation of PSADT: 
PSADT will be derived based on the PSA measurements provided by the investigator in 
the database and collected during the trial at screening visit and during each cycle. 
PSADT will be calculated post-treatment on C4D1 and D1 of every fourth subsequent 
cycle (e.g. C8D1, C12D1, etc.) in Part 1 and Part 2 Arms 1A and 1B, or on C4D1, C8D1, 
and EoT in Part 2 Arms 2 and 3. 


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PSA measurements reported after EoT visit or after start of the first subsequent anti-
cancer therapy will not be considered in the derivation of PSADT.  
PSADT will be calculated using a linear regression model of the natural logarithm of PSA 
values and time ([3] and [https://drhaddad.com.au/wp-content/uploads/2022/07/13.pdf], [8]. 
 
Derivation of PSADT post-treatment at every fourth subsequent cycle: 
1. Compute the slope of the regression line of natural logarithm of PSA vs. time (which is 
the number of doublings per unit time) where PSA is the PSA level in ng/mL at each 
time point 
2. Compute PSADT (days) = natural log (2) / slope, 
natural log (2) = 0.693. 
3. Multiply PSADT (days) by 12/365.25 to get PSADT (months) 
 
The calculation of post-treatment PSADT should be based on (1) at least 3 consecutive 
PSA values with each value >= 0.2 ng/dL (or >= 0.002 ng/mL), (2) inclusion of the most 
recent PSA values during androgen deprivation therapy, and (3) interval between first and 
last PSA value of >= 8 weeks but <= 12 months.  
8.3 
Missing Data 
All reasonable efforts will be made to obtain complete data for all patients. However, 
missing observations may occur due to patients lost to follow-up or to noncompliance with 
required trial visits and / or assessments. Missing data will not be imputed and data 
analysis will be performed based on the observed values, unless otherwise specified. 
8.4 
Visit Windows 
Every attempt should be made to perform evaluations at the designated time point / visit. 
Visit windows for visits per cycles, for Safety FU visits, and for Efficacy FU visits are 
defined in the SoA (see Section 13.6). All visits will be summarized according to the 
nominal visit. 
8.5 
Patient disposition 
Patient disposition will be summarized by presenting the number and percentage of 
patients screened, re-screened, number of screening failures, along with a summary of the 
primary reason for screening failure for the screened set.  
The number and percentage of patients eligible to participate in the trial, number of 
randomized patients (for Part 2), and the number and percentage of patients in each 
analysis set will be summarized by treatment group for the patients in the screened set.  
For each analysis set (e.g., ITT set, mITT set, Safety set, PP set and Pharmacodynamic 
set) the number and percentage of patients being excluded from the analysis set will be 
presented by treatment group along with a summary of the reasons for exclusion based on 


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the ITT set. In addition, the number of patients in the subsequent cemiplimab monotherapy 
on progression set will be reported. 
The number and percentage of screened / randomized / treated patients will be presented 
by country and site including the number and percentage of patients with important 
protocol deviations (by treatment group) for the screened set.  
For the ITT set the treatment status will be reported, including the number and percentage 
of patients having prematurely discontinued treatment by treatment group along with a 
summary of the primary reason for premature treatment discontinuation of W_pro1 
treatment, of cemiplimab treatment and of ADT treatment (e.g., completed per protocol, 
AEs, disease progression, death, withdrawal of consent, lost to follow-up), as applicable. 
Further, the number and percentage of patients started follow- up period, and end of trial 
disposition will be reported including the number and percentage of patients having 
completed or discontinued the trial with a summary of the primary reason for trial 
discontinuation including the number of deaths.  
Important protocol deviations will be summarized for the ITT set by treatment group. In 
addition, a table will be generated summarizing the number and percentage of patients 
with a protocol deviation due to COVID-19 for the ITT set. 
All data will be listed (patient disposition listing, protocol deviation listing, protocol deviation 
due to COVID-19 listing), and a listing of all patients excluded from any of the analysis sets 
including the primary reason for exclusion from the analysis sets.  
In addition, a listing of all inclusion and exclusion criteria which were not met, based on the 
screened set will be generated. 
Further, the following listings will be generated for the ITT set to report the impact of 
COVID-19 to patients enrolled in this trial: 
• 
Patients impacted by COVID-19 related trial disruption 
• 
Missing Visits due to COVID-19 
8.6 
Baseline characteristics 
8.6.1 
Demographics 
Demographic and baseline variables will be summarized for patients in the mITT set. Age 
(years), weight (kg), height (cm), body mass index (kg/m2) and Glomerular filtration rate 
(mL/min/1.73 m2) will be summarized as continuous data. Age (< 50 years, >= 50 - <65 
years, >= 65 years), Gender (must be male), Ethnicity (Hispanic or Latino, Not Hispanic or 
Latino, Not Reportable), race (White, Black or African American, Asian, American Indian or 
Alaska Native, Native Hawaiian or Other Pacific Islander, Not Reportable, Unknown, 
Other) and BMI categories (<18 kg/m2, >=18 kg/m2 - <25 kg/m2, >=25 kg/m2 - <30 
kg/m2, >=30 kg/m2) will be summarized as categorical data.  
 
Demographic tables for the ITT set, Safety set and the PP set will be generated, 
depending on the number of patients excluded from the respective analysis set. 


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A listing of demography will be provided for the ITT set. 
8.6.2 
Disease characteristics 
Disease characteristics will be summarized for patients in the mITT set. Time from initial 
diagnosis to enrollment will be summarized as continuous data. Tumor stage at diagnosis, 
tumor grade (Gleason Score) at diagnosis, National Comprehensive Cancer Network 
(NCCN) Risk Group at diagnosis, PSA level at diagnosis (ng/mL), prostate cancer 
diagnosis at screening (mCRPC, LPC), tumor stage at screening, ECOG performance 
status at baseline, tetanus vaccination status, histology will be summarized as categorical 
data.  
Further, on the basis of the initial tumor response assessment (based on PCWG3) 
reported at the Screening visit, the following variables will be reported: 
- 
Disease Characteristics – Imaging: Target Lesions (Absent / Present), Non-Target 
Lesions (Absent / Present), Locations of Target Lesions (Anus, Abdominal Cavity, 
Other - as collected in the database) and Sum of target lesion diameters. 
 
Further information regarding bone lesions at screening to be reported: 
Bone-only disease (patients with no target and no non-target lesion at screening 
evaluation, only bone lesions reported), Bone lesions (Yes, No), in case of “Yes” the total 
number of lesions related to metastatic disease (1, 2-4, 5-9, 10-20, >20). 
 
Visceral metastasis (Yes, No) defined based on the location of target or non-target lesions 
at screening evaluation. For more details see Section 13.5.  
Further the number of patients with at least one visceral metastasis (target or non-target 
lesions) in liver and lung separately, will be reported. 
Lymph node metastasis (Yes, No) defined based on the location of target or non-target 
lesions at screening evaluation with location = Lymph Node. 
Disease characteristics data will be listed for the ITT set. 
8.6.3 
Prior anti-cancer treatments 
The following prior anti-cancer therapies will be summarized using frequency tables for the 
mITT set. 
• 
Prior cancer surgery 
• 
Prior cancer radiotherapy 
• 
Prior systemic cancer therapy 
Prior cancer surgeries will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA version 22.1 or later version). 
Prior systemic cancer therapies will be coded using the World Health Organization Drug 
Dictionary (WHO-DD) drug codes of the most recent version (WHO-DD Global B3 Sep 


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2019, or later version) resulting in Anatomical-Therapeutic-Chemical (ATC) codes 
indicating therapeutic classification. 
The number and percentages of patients with any prior cancer surgery will be summarized 
by System Organ Class (SOC) and Preferred Term (PT) for each treatment group.  
All prior cancer therapy types as specified below: 
A table “Prior Therapy Lines” will be generated including: 
• 
Number of prior systemic cancer therapies per patient, setting of last systemic cancer 
therapy (adjuvant, neoadjuvant, palliative, other, unknown), disease status at the end 
of the last prior systemic cancer therapy (CR, PR, PD, SD, NE, Unknown, Non-
Progressive disease), Reasons for termination of the last prior systemic cancer therapy 
(AE, Disease Progression, Other, Unknown, Completion of therapy) 
A table “Prior Therapy Types” will be generated including the number of patients and 
percentages of  
• 
Any prior cancer surgery including information of treatment intent (palliative, curative, 
diagnostic, unknown) 
• 
Any prior cancer radiotherapy including information of site and setting (adjuvant, 
neoadjuvant, palliative, curative, unknown) 
• 
Any prior systemic cancer therapy including information of setting (adjuvant, 
neoadjuvant, palliative, other, unknown)  
• 
Number of patients with any prior systemic cancer therapy with Docetaxel or other 
Taxanes. (Use ATC Level 4 Code = L01CD (Taxanes) for the derivation) 
• 
Number of patients with any prior systemic cancer therapy with ADT or Degarelix.  
(Use ATC Level 4 Code = L02AE (Gonadotropin releasing hormone analogues), to 
identify all ADTs,  
L02BX (Other hormone antagonists and related agents) and standardized medication 
name = Degarelix or Degarelix acetate for the selection of Degarelix.) 
Including details of Adjuvant or Neo-adjuvant ADT or Degarelix therapy 
• 
Number of patients with any prior systemic cancer therapy: Novel hormone therapies 
(Use ATC Level 4 Code = L02BB (Anti-Androgens) and L02BX (Other hormone 
antagonists and related agents), except medication name = Degarelix or Degarelix 
acetate) 
Prior cancer surgery, prior cancer radiotherapy and prior systemic cancer therapy will be 
listed for the ITT set. 
8.6.4 
Prior and concomitant medication 
All medications will be coded using the WHO-DD drug codes of the most recent version 
(WHO-DD Global B3 Sep 2019, or later version) resulting in ATC codes indicating 
therapeutic classification. 
Prior and concomitant medications will be defined using start and stop dates recorded, 
relative to the first and last IMP administration dates.  


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A prior medication will be defined as any therapy taken prior up to (but not including) the 
start date of first IMP administration.  
A concomitant medication will be defined as any medication either ongoing at the start 
date of first IMP administration or with a start date on or after the first IMP administration 
date up to (but not including) the Safety FU-D30 or Safety FU-D90 visit as appropriate. 
The number and percentage of patients taking prior medication or concomitant 
medications will be summarized by ATC therapeutic class (ATC level 2), ATC 
pharmacological class (ATC level 3), and chemical substance (ATC level 4) for each 
treatment group based on the mITT set. 
A listing of prior and concomitant medications will be provided for the ITT set. 
In addition, a listing of further antineoplastic therapies after discontinuation of IMPs, as 
collected in the eCRF, will be generated. 
8.6.5 
Other Procedures 
Concomitant cancer radiotherapy:  
During the course of the trial concomitant new cancer radiotherapies within 28 days prior 
to start of first IMP administration up to (but not including) the Safety FU-D30 or Safety FU-
D90 Visit as appropriate will be reported.  
A summary table presenting the number and percentage of patients with any concomitant 
cancer radiotherapy, including information of site will be summarized by treatment group 
for the mITT set. All data will be listed for the ITT set. 
Concomitant Procedures and Non-Drug Therapies: 
During the course of the trial concomitant procedures/non-drug therapies, e.g. invasive 
procedures / surgery, may take place and will be documented on the eCRF page 
“Procedures / Non-Drug Therapies”. Data will be reported within 28 days prior to start of 
the first administration of IMP up to (but not including) the Safety FU-D30 or Safety FU-
D90 Visit as appropriate will be reported. Procedures and Non-Drug Therapies will be 
coded using MedDRA (version 22.1 or later version).  
The number and percentages of patients with any concomitant procedures/non-drug 
therapies will be summarized by SOC and PT for each treatment group for the mITT set. 
All data will be listed for the ITT set. 
8.6.6 
Medical history 
Medical history data will be coded using MedDRA (version 22.1 or later version). The 
number and percentage of patients with a medical history (prior medical history and 
concomitant diseases) will be summarized by SOC and PT. This summary will be done by 
treatment group for patients in the mITT set. 
Medical history terms with ongoing ticked “No” will be considered as prior medical history, 
with ongoing ticked “Yes” as concomitant diseases. 
A listing of medical history data will be provided for the ITT set. 


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8.7 
Efficacy analyses 
8.7.1 
Primary analysis 
8.7.1.1 
Primary Efficacy Endpoint 
Objective Response Rate 
For Part 2, Arms 1A and 1B, ORR is defined as primary efficacy endpoint. The primary 
analysis will be performed using the mITT set. 
The ORR is defined as the number of patients with CR or PR as best objective response 
per PCWG3 divided by the number of patients in the mITT set. Patients not meeting the 
criteria for CR or PR, including those without any post-baseline response assessments, 
will be considered as non-responders. The ORR will be summarized with absolute and 
relative frequencies along with two-sided 95% Clopper-Pearson CIs by treatment group.  
For each Part 2 Arm 1A and 1B the null hypothesis (see Section 4) that the true response 
rate is 5% will be tested against a one-sided alternative (i.e. H0: ORR=5% versus H1: ORR 
>5%). There will be no formal comparison between treatment groups. 
BOR (all categories) based on PCWG3 will be summarized with absolute and relative 
frequencies. 
Further, the BOR (all categories) based on Radiological Soft Tissue Evaluation will be 
summarized with absolute and relative frequencies. 
For Part 1, ORR is defined as secondary endpoint as best objective response and will be 
analyzed descriptively. 
Tumor response assessment including overall response, BOR and clinical progression as 
documented in the eCRF will be listed. In addition, listings including all tumor assessments 
per PCWG3 (target lesion, non-target lesion, new lesion) will be generated. 
Subgroup analyses of the primary efficacy endpoint will be performed for the mITT set. 
Sensitivity analysis 
For the primary endpoint ORR, sensitivity analyses will be performed using the ITT set and 
the PP set. 
8.7.2 
Supplementary analyses 
Not applicable. 
8.7.3 
Secondary analyses 
8.7.3.1 
Secondary efficacy endpoints 
Prostate-specific antigen decline  
PSA will be collected for all patients in Part 1 and Part 2 at several visits during the course 
of the trial (see SoA in Section 13.6 for more details). PSA values will be provided by a 
central laboratory and reported by the investigator in the database. For the analyses, it 


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was agreed to use the PSA measurements as provided by the investigator together with 
the PSA response per PCWG3 criteria as reported in the database. 
PSA decline calculated as percentage change compared to baseline will be summarized 
using descriptive summary statistics for each visit by treatment group. 
PSA decline of 0 to 25%, > 25% to 50%, and > 50% compared with baseline and PSA 
decline of <50% versus >=50% compared to baseline will be summarized with absolute 
and relative frequencies (n and %) of patients by visit and treatment group for the mITT 
set.  
Bar charts for PSA decline compared to baseline in the above defined categories by visit 
will be generated for the mITT set. 
Waterfall plots for maximum PSA decline from baseline per patient will be generated.  
For the derivation of maximum decline from baseline only measurements which were 
reported >= 4 weeks after treatment start and prior to or at the EoT visit and prior to or at 
the start date of the subsequent anti-cancer therapy to be considered. Only PSA 
measurements corresponding to a confirmed PSA response (see Section 8.2 for the 
definition of confirmed PSA response) or reported after a confirmed PSA response have to 
be considered in the derivation of maximum PSA decline (an initial PSA response will 
confirm all subsequent PSA responses of the same response value, as long as there is not 
a better or worse response between them). 
PSA response per PCWG3 criteria (as reported by the investigator) will be summarized 
with absolute and relative frequencies (n and %) of patients by visit and treatment group 
for the mITT set. 
Best overall PSA response, ORR and Clinical Benefit Rate (CBR) per PCWG3 criteria will 
be summarized for the mITT set. 
Sensitivity analyses for PSA decline will be performed using the ITT set and the PP set 
depending on the number of patients excluded. 
 
Prostate-specific antigen doubling time 
The number and percentage of patients per PSADT under-treatment on C4D1 and D1 of 
every fourth subsequent cycle (e.g., C8D1, C12D1, etc.) in Part 1 and Part 2 Arm 1A and 
1B, or on C4D1, C8D1, and EoT in Part 2 Arms 2 and 3 compared with baseline. For more 
details for the calculation of PSADT, see Section 8.2.  
The following categorization of PSADT should be reported: 0 - 3 months, >3 – 6 months, 
>6 – 9 months, >9 – 12 months , >12 – 18 months, >18 – 24 months, >24 months. 
Sensitivity analyses will be performed using the ITT set and the PP set depending on the 
number of patients excluded. 
 
Objective Response Rate for Part 1 


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For Part 1, ORR is defined as secondary efficacy endpoint as best objective response per 
PCWG3 and will be analyzed descriptively for the mITT set. For more details, see 
Section 8.7.1.1. 
Tumor assessment post-treatment compared to baseline for Part 2, Arm 2 and Arm 
3 
Tumor measurements using mpMRI or, if tumor measurement is not feasible with a 
mpMRI, imaging according to local practice (e.g. CT or MRI), should be performed at the 
following time points: 
• 
During the screening period (within 28 days before C1D1 (baseline) 
• 
Prior to surgery (i.e. at the end of C8/EoT Visit) 
Tumor response will be assessed based on Radiological Soft Tissue Evaluation at both 
time points. Number of patients in each category and ORR will be summarized with 
absolute and relative frequencies along with two-sided 95% Clopper-Person CIs by 
treatment group for the mITT set. 
Tumor response assessment including overall response, best overall response and clinical 
progression as documented in the eCRF will be listed. In addition, listings including all 
tumor assessments per PCWG3 (target lesion, non-target lesion, new lesion) will be 
generated. 
Sensitivity analyses will be performed using the ITT set and the PP set depending on the 
number of patients excluded. 
8.7.4 
Exploratory analyses 
Exploratory efficacy analyses will be performed using the mITT set. 
Exploratory efficacy endpoints comprise ORR (in the mCRPC arms and only per 
iRECIST), DoR, PFS, and OS. Tumor assessments will be performed using PCWG3 for all 
patient in Part 1 and Part 2 of the trial. For mCRPC patients enrolled in Part 1 and Part 2, 
tumor assessment using iRECIST (central reading) will be performed in addition.  
For mCRPC patients enrolled in Part 1 and Part 2, ORR, DoR, and PFS will be analyzed 
separately for PCWG3 and iRECIST (central reading). 
ORR, and DoR will be analyzed for Part 1 and Part 2 Arms 1A and 1B only.  
Sensitivity analyses for exploratory endpoints will be performed using the ITT set and the 
PP set depending on the number of patients excluded. 
In addition, subgroup analyses for some of the exploratory endpoints (i.e. DoR and PFS) 
will be performed based on the mITT set. The final decision will be made during the DRM. 
Exploratory efficacy analyses will also be performed on patients in Arm 1B who are treated 
with cemiplimab monotherapy following progression after W_pro1 monotherapy. These 
exploratory analyses will comprise ORR, DoR, PFS (per PCWG3 and iRECIST (central 
reading)) on cemiplimab monotherapy based on last tumor assessment prior to start of 
cemiplimab treatment and OS. PFS2 will be analyzed as well. These exploratory efficacy 


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analyses will be performed using the subsequent cemiplimab monotherapy on progression 
set. 
Exploratory immunogenicity analyses of W_pro1 antigen-specific T-cells based on 
ELISPOT and further immune monitoring data are not part of this SAP. Respective data 
will be provided by a central laboratory. 
8.7.4.1 
Exploratory efficacy endpoints 
Objective Response Rate based on iRECIST (central reading) 
ORR based on iRECIST will be analyzed for mCRPC patients in Part 1 and Part 2 only. 
The ORR is defined as the number of patients with iCR or iPR as best objective response 
per iRECIST divided by the number of patients in the mITT set. Patients not meeting the 
criteria for iCR or iPR, including those without any post-baseline tumor assessments, will 
be considered as non-responders. The ORR will be summarized with absolute and relative 
frequencies along with two-sided 95% Clopper-Pearson CIs by treatment group.  
BOR (all categories) will be summarized with absolute and relative frequencies. 
Tumor response assessment including overall response and BOR will be listed. In 
addition, listings including all tumor assessments per iRECIST (central reading) (target 
lesion, non-target lesion, new lesion) will be generated. 
Duration of Response 
DoR will be analyzed for Part 1 and Part 2 Arms 1A and 1B only. DoR will be analyzed 
separately for PCWG3 and iRECIST (central reading). 
The DoR is defined as the time from the date of first radiographic documented OR to the 
date of first disease progression or death from any cause, whichever occurs first. Only 
patients who experience a confirmed OR will be analyzed for DoR.  
In case death date is reported after trial discontinuation date, these death details will not 
be considered in the DoR analysis. The patient will be censored at the day of the last 
response assessment. 
DoR will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated. 
Patients alive and without disease progression at data cut-off date or patients lost to 
follow-up will be censored at the day of their last response assessment.  
Only response assessments prior to or at the start date of the first subsequent anti-cancer 
therapy will be considered for DoR analysis. PD within 14 days after the start date of the 
first subsequent anti-cancer therapy will be considered. 
DoR based on PCWG3: 
OR is defined as CR or PR. Disease progression is defined as tumor response = 
Progressive Disease (PD) 


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DoR expressed in months for patients whose objective response was confirmed CR or PR 
= (MIN [Date of first documented disease progression (PD), date of death from any cause] 
– Date of first documented overall response (CR or PR) + 1) / 30.4375 for events  
or  
(Date of the last evaluable response assessment – Date of first documented overall 
response (CR or PR) + 1) / 30.4375 in case of censoring. 
 
DoR based on iRECIST (central reading): 
OR is defined as iCR or iPR. Disease progression is defined as tumor response = 
Confirmed progressive disease (iCPD) 
DoR expressed in months for patients whose objective response was confirmed iCR or 
iPR = (MIN [Date of first documented disease progression (iCPD), date of death from any 
cause] – Date of first documented overall response (iCR or iPR) + 1) / 30.4375 for events  
or  
(Date of the last evaluable response assessment – Date of first documented overall 
response (iCR or iPR) + 1) / 30.4375 in case of censoring. 
Progression-free survival  
PFS will be analyzed for Part 1 and Part 2 Arms 1A and 1B, Arm 2 and Arm 3. 
PFS is defined as the time from the date of the first dose of IMP to the date of the first 
disease progression, or death from any cause, whichever occurs first.  
Only death dates reported prior to or at the date of trial discontinuation will be considered 
in the PFS analysis. 
PFS will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated.  
Patients alive and without disease progression at the data cut-off date or patients lost to 
follow-up will be censored at the day of their last response assessment.  
Only response assessments prior to or at the start date of the first subsequent anti-cancer 
therapy will be considered for PFS analysis. PD within 14 days after the start date of the 
first subsequent anti-cancer therapy will be considered. 
If no post-baseline tumor response is available, the patient will be censored at the date of 
the first dose of IMP.  
PFS expressed in months = (MIN [Date of first disease progression, date of death from 
any cause] – date of first dose of IMP + 1) / 30.4375 if the patient has a PFS event 
or  
(Date of last evaluable response assessment – date of first dose of IMP + 1) / 30.4375 in 
case of censoring. 


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In the case that date of the first dose of IMP is missing, randomization date will be used for 
the calculation of PFS. 
For Part 1 and Part 2 Arms 1A and 1B, PFS will be analyzed separately based on PCWG3 
and iRECIST (central reading).  
Sensitivity analyses of PFS will be performed using the ITT set and the PP set depending 
on the number of patients excluded.  
Overall survival 
OS will be analyzed for Part 1 and Part 2 Arms 1A and 1B, Arm 2 and Arm 3. 
OS is defined as the time from the date of the first dose of IMP to the date of death from 
any cause. OS will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated.  
In case date of death is reported after trial discontinuation date, this data will not be 
considered in the OS and the patient will be censored at the day of their last date known to 
be alive. 
Patients alive or patients lost to follow-up at the date of analysis cut-off will be censored at 
the day of their last date known to be alive.  
OS expressed in months = (Date of death from any cause – date of first dose of IMP + 1) / 
30.4375 for patients with available death date 
or  
(Last date of known to be alive – date of first dose of IMP + 1) / 30.4375 in case of 
censoring. 
In the case that date of the first dose of IMP is missing, randomization date will be used for 
the calculation of OS. 
8.7.4.2 
Exploratory efficacy endpoints for patients in Arm 1B who are treated 
with cemiplimab monotherapy following progression on W_pro1 
Patients in Arm 1B will be given the option to be treated with cemiplimab monotherapy 
following progression on W_pro1 monotherapy treatment and will be assessed for some 
exploratory efficacy endpoints, where the last measurement prior to start of cemiplimab 
treatment will serve as baseline measurement and the time-to-event endpoints (DoR, and 
PFS) will start from first dose of cemiplimab treatment. In particular, the last radiographic 
tumor assessment prior to cemiplimab treatment will re-define target and non-target 
lesions as basis for tumor response assessment on cemiplimab treatment. Additionally, 
PFS2 will be evaluated based on initial start of IMP.  
These exploratory efficacy analyses will be performed using the subsequent cemiplimab 
monotherapy on progression set. 
Objective Response Rate based on PCWG3 and iRECIST (central reading)   
ORR will be analyzed separately for PCWG3 and iRECIST (central reading).  


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The ORR is defined as the number of patients with CR or PR as best objective response 
per PCWG3 (or number of patients with iCR or iPR as best objective response per 
iRECIST (central reading)) after start of cemiplimab treatment, divided by the number of 
patients in the subsequent cemiplimab monotherapy on progression set.  
Patients not meeting the criteria for CR or PR (iCR or iPR per iRECIST (central reading)), 
including those without any post-baseline response assessments, will be considered as 
non-responders. The ORR will be summarized with absolute and relative frequencies 
along with two-sided 95% Clopper-Pearson CIs.  
BOR (all categories) will be summarized with absolute and relative frequencies. 
Duration of Response based on PCWG3 or iRECIST (central reading) 
DoR will be analyzed separately for PCWG3 and iRECIST (central reading). 
The DoR is defined as the time from the date of first radiographic documented OR to the 
date of first disease progression or death from any cause, whichever occurs first. Only 
patients who experience a confirmed OR after start of cemiplimab treatment will be 
analyzed for DoR.  
Only death dates reported prior to or at the date of trial discontinuation will be considered 
in the DoR analysis. 
DoR will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated. 
Patients alive and without disease progression at data cut-off date or patients lost to 
follow-up will be censored at the day of their last response assessment.  
Only response assessments prior to or at the start date of the first subsequent anti-cancer 
therapy will be considered for DoR analysis. PD within 14 days after the start date of the 
first subsequent anti-cancer therapy will be considered. 
DoR based on PCWG3: 
OR is defined as CR or PR. Disease progression is defined as tumor response = 
Progressive Disease (PD) 
DoR expressed in months for patients whose objective response was confirmed CR or PR 
after start of cemiplimab treatment =  
(MIN [Date of first documented disease progression (PD) after start of cemiplimab 
treatment, date of death from any cause] – Date of first documented overall response (CR 
or PR) + 1) / 30.4375 for events  
or  
(Date of the last evaluable response assessment after start of cemiplimab treatment – 
Date of first documented overall response (CR or PR) + 1) / 30.4375 in case of censoring. 
DoR based on iRECIST (central reading): 
OR is defined as iCR or iPR. Disease progression is defined as tumor response = 
Confirmed progressive disease (iCPD) 


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DoR expressed in months for patients whose objective response was confirmed iCR or 
iPR after start of cemiplimab treatment =  
(MIN [Date of first documented disease progression (iCPD) after start of cemiplimab 
treatment, date of death from any cause] – Date of first documented overall response (iCR 
or iPR) + 1) / 30.4375 for events  
or  
(Date of the last evaluable response assessment after start of cemiplimab treatment – 
Date of first documented overall response (iCR or iPR) + 1) / 30.4375 in case of censoring. 
Progression-free survival based on PCWG3 or iRECIST (central reading) 
PFS will be analyzed separately for PCWG3 and iRECIST (central reading). 
PFS is defined as the time from the date of the first dose of cemiplimab treatment to the 
date of the first disease progression, or death from any cause, whichever occurs first.  
Only death dates reported prior to or at the date of trial discontinuation will be considered 
in the PFS analysis.  
PFS will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated.  
Patients alive and without disease progression after start of cemiplimab treatment at the 
data cut-off date or patients lost to follow-up will be censored at the day of their last 
response assessment.  
Only response assessments prior to or at the start date of the first subsequent anti-cancer 
therapy will be considered for PFS analysis. PD within 14 days after the start date of the 
first subsequent anti-cancer therapy will be considered. 
If no post-baseline response assessment after start of cemiplimab treatment is available, 
the patient will be censored at the date of the first dose of cemiplimab treatment.  
PFS expressed in months = (MIN [Date of first disease progression after start of 
cemiplimab treatment, Date of death from any cause] – date of first dose of cemiplimab 
treatment + 1) / 30.4375 if the patient has a PFS event 
or  
(Date of last evaluable response assessment after start of cemiplimab treatment – date of 
first dose of cemiplimab treatment + 1) / 30.375 in case of censoring. 
Progression-free survival 2 (PFS2) based on PCWG3 
PFS2 is defined as the time from the date of the first IMP to the date of the first disease 
progression after start of cemiplimab per PCWG3, or death from any cause, whichever 
occurs first.  
Only death dates reported prior to or at the date of trial discontinuation will be considered 
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PFS2 will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated.  
Patients alive and without disease progression after start of the first IMP at the data cut-off 
date or patients lost to follow-up will be censored at the day of their last response 
assessment. Only response assessments prior to or at the start date of the first 
subsequent anti-cancer therapy will be considered for PFS2 analysis. PD within 14 days 
after the start date of the first subsequent anti-cancer therapy will be considered. 
If no post-baseline response assessment after start of cemiplimab treatment is available, 
the patient will be censored at the date of the first dose of cemiplimab treatment.  
PFS2 expressed in months = (MIN [Date of first disease progression after start of 
cemiplimab treatment, Date of death from any cause] – date of first dose IMP + 1) / 
30.4375 if the patient has a PFS2 event 
or  
(Date of last evaluable response assessment after start of cemiplimab treatment – date of 
first dose of IMP + 1) / 30.375 in case of censoring. 
Overall survival for the subset of patients in Arm 1B who are treated with 
cemiplimab monotherapy 
OS is defined as the time from the date of first dose of IMP to the date of death from any 
cause. OS will be analyzed using the Kaplan-Meier method. Kaplan-Meier plots will be 
generated. OS expressed in months will be derived as defined in Section 8.7.4.1. 
8.7.5 
Further efficacy analyses 
Survival status and biochemical recurrence 
Survival status will be assessed at month 6 and month 12, beginning from the day of the 
last IMP dose and continues until the patient dies or withdrawal from the trial. 
Disease status (CR, PR, SD, PD, Unknown) will be collected for all patients in Part 1 and 
Part 2 on the survival follow-up CRF page and will be summarized with absolute and 
relative frequencies at time points as collected during the survival follow-up reporting 
period. 
Biochemical recurrence after radical prostatectomy based on the post-treatment PSA 
levels at Efficacy FU Month 6 and FU Month 12 will be summarized for patients in Arms 2 
and 3. 
For LPC patients (Arm 2 and Arm 3) the time (in days) from treatment start to post 
treatment prostatectomy will be reported. 
8.7.6 
Interim analysis for futility 
An interim statistical analysis for futility is planned for Part 2, Arm 1A and Arm 1B based on 
the Simon's two-stage design (Simon, 1989 [5], see Section 6).  


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Simon's two-stage design based on the Minimax approach will be used for Arm 1A and 
Arm 1B separately. The null hypothesis that the true response rate is 5% will be tested 
against a one-sided alternative.  
In the first stage, 20 patients will be enrolled. Enrollment will continue until the SRC 
decision and 13 additional patients may be accrued for a total of 33.  
The interim analysis will be performed based on all available data from a clinical data cut-
off that will occur when the required number of patients in the respective arm (Arm 1A and 
1B) have performed the first post-baseline tumor assessment based on PCWG3 or 
discontinued before; tumor assessment scheduled every 8 weeks for the first 24 weeks 
and every 3 months thereafter. 
One interim analysis is planned, where the decision for both treatment Arms 1A and 1B 
will be made.  
If there are 1 or fewer responses in the first 20 patients in Part 2, Arm 1A or Arm 1B, the 
enrollment for that arm may be stopped. In case there are no responses reported in the 
first 19 patients in the respective treatment arms, the sponsor will check and decide if 
enrollment should stop for futility and no 20th patient to be included. 
A patient will be considered as a responder if the best objective response per PCWG3 is 
CR or PR. All other patients or patients without any post-baseline tumor assessments will 
be considered as non-responders. Interim analysis will be performed on the mITT set. 
A predefined set of TFLs to be generated for the interim analysis is defined in Section 11. 
After the interim analysis performed in August 2022 (using a data cut-off date = 
01 JUN 2022), the sponsor decided to stop enrollment of mCRPC patients in Part 2 Arms 
1A and 1B. 
8.8 
Pharmacodynamic analyses 
Blood samples and tumor samples for biomarker analysis are collected from patients with 
mCRPC (Part 1 and Part 2 Arms 1A and 1B) and LPC (Part 2 Arms 2 and 3) at time points 
shown in the SoA (see Section 13.6). Biomarker and pharmacodynamics parameters are 
analyzed by different laboratories (central laboratory and speciality laboratories). 
8.8.1 
Pharmacodynamic parameters 
Clinical and immunological parameters assessed by qualified assays will be measured as 
part of Pharmacodynamic set and correlated with clinical response and outcome. As part 
of this SAP, the following listings will be provided for the Pharmacodynamic set: 
 
Blood 
Hormones (Testosterone): 
Cytokines: 
Interferon Alpha, Interleukin 6, Interleukin 10, Interferon Gamma, Interferon Gamma-
induced Protein 10, Tumor Necrosis Factor alpha 
Tumor response and extension  


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Tissue (only 
available for LPC 
patients) 
Immune cell infiltration in tumor bed 
8.8.2 
Exploratory Biomarker Analyses 
Cellular immune responses and further immunological parameters will be analyzed as part 
of exploratory objective to identify potential predictive, pharmacodynamic, anti-tumor and 
safety biomarkers indicating activity of W_pro1 monotherapy or in combination with 
cemiplimab. The analyses except those for cytokines are not part of this SAP. 
Table 8-1 provides an overview of the biomarker parameters: 
Table 8-1: Biomarker Assessment - Overview 
Rationale 
Test 
Safety 
Cytokines: 
Interferon Alpha, Interleukin 6, Interleukin 10, Interferon Gamma, Interferon 
Gamma-induced Protein 10, Tumor Necrosis Factor alpha  
MoA/PD 
Cellular immune response (Immunogenicity by Post IVS ELISpot) 
MoA/PD 
HLA typing: 
HLA DP Beta1 Antigen, HLA DQ Beta1 Antigen, HLA DR Beta1 Antigen, HLA 
Class IA Antigen, HLA Class IB Antigen, HLA Class IC Antigen. 
Tumor associated antigen profile (PSA, ACPP, HOXB13, KLK2, NKX3-1) 
MoA/PD 
T cell profiling, TCR discovery & profiling, Reverse Immune Monitoring,  
MoA/PD 
Tumor composition, mutation burden & transcriptome (RNA) 
HLA = human leukocyte antigen; ICS = intracellular cytokine staining; MoA/PD = mechanism (mode) of 
action/pharmacodynamics; TCR = T cell receptor. 
 
The following exploratory endpoints based on biomarkers and pharmacodynamics 
parameters will be analyzed: 
• 
Status of tumor mutational burden and immune-related gene expression (at the RNA 
level) in tumor tissue prior to treatment. 
• 
Change in protein expression pattern/levels of tumor microenvironment markers (e.g., 
CD3, CD8, MHC-I, PD-L1, etc.) and prostate tumor markers (e.g., PSA, PSAP, NKX3-
1, etc.) in tumor tissue post-treatment compared to baseline. 
• 
Baseline status or change in RNA target expression of W_pro1–encoded antigens in 
the post-treatment tissue compared to baseline.  
• 
Change in T cell clonality/diversity post-treatment compared to baseline. 
• 
Changes in blood biomarkers prior to and during trial treatment. 
These exploratory biomarker and pharmacodynamics analyses are not part of this SAP.  
The respective analysis will be specified and performed in the context of the exploratory 
BioNTech biomarker report. 
 


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8.9 
Safety analyses 
Safety data that will be summarized include extent of exposure, AEs, occurrence of DLTs 
during Part 1, clinical laboratory assessments, vital signs and body weight, ECGs, physical 
examination and ECOG performance status (ECOG PS). All safety analyses will be based 
on the safety set and will be summarized by treatment groups, and for several combined 
treatment groups as defined in Section 13.4, unless otherwise stated.  
Patients will be assigned to the treatment groups according to the actual treatment they 
have received (“as treated”).  
All safety data will be listed for the safety set. 
8.9.1 
Primary safety endpoints dose-limiting toxicities and treatment-
emergent adverse events 
The primary endpoint is the occurrence of DLTs and TEAEs reported by relationship, 
grade, and seriousness according to NCI CTCAE v5.0. The number and percentage of 
patients with any DLT only for Part 1, and/or TEAEs in Part 1 and Part 2 will be presented.  
Moreover, a patient listing will be provided with all relevant dose exposure data of all 
patients enrolled into Part 1 and Part 2, and a listing of all recorded DLTs and/or AEs will 
be presented including the reported term and SOC and PT terms coded usingMedDRA®, 
its time of onset, relationship, NCI CTCAE grade, and seriousness including dose 
exposure data (e.g., W_pro1 DL).  
The respective analyses are specified in Section 8.9.3. 
8.9.2 
Extent of exposure 
The following dose-exposure variables will be derived and analyzed for each IMP 
compound (W_pro1 and cemiplimab). The respective analyses for  ADT are depending on 
the different kinds of ADT administered during the trial and will be defined at a later stage: 
• 
Number of cycles (Total) 
• 
Number of cycles with W_pro1, Number of cycles with cemiplimab, Number of ADT 
administrations 
• 
Number of patients who stopped Part 2 mCRPC W_pro1 and switch to cemiplimab 
monotherapy  
• 
Actual Treatment duration (weeks) for each compound defined as follows:  
(Date of last administration - date of first administration +1 + planned duration)/7, 
whereas the planned duration (days) is defined as the planned time between two 
consecutive administrations. 
Planned duration for cemiplimab is 21 days (to be used for the calculation of actual 
treatment duration). 
Planned duration for W_pro1 in the first 2 cycles is 7 days because there are 
3 treatment administration planned (one every 7 days). Starting from Cycle 3 onwards, 


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the planned duration of W_pro1 is 21 days (only one treatment administration per 
cycle). To be used for the for the calculation of actual treatment duration. 
ADT: Treatment duration (weeks): (Date of last administration - date of first 
administration + 1) / 7. 
• 
Actual Cumulative Dose (µg) is defined as sum of all administered doses separate for 
W_pro1 (µg), cemiplimab (mg) and ADT (mg).  
Dose Intensity (DI), Relative Dose Intensity (RDI), planned cumulative dose and 
planned treatment duration for W_pro1 and cemiplimab are defined as follows: 
• 
DI is defined as Cumulative Dose (µg)/Treatment Duration (weeks) 
• 
RDI is defined as follows: 
RDI (%) =
Actual Dose Intensity ቀµg
weekቁ
Planned Dose Intensity ቀµg
weekቁ
 x 100 = DI x TI x 100,  
whereas 
(Actual) Dose Intensity ቀµg
weekቁ=
(Actual) Cumulative Dose (µg)
(Actual) Treatment Duration (weeks)  
Planned Dose Intensity ቀµg
weekቁ=
Planned Cumulative Dose (µg)
Planned Treatment Duration (weeks)  
Dose Index (DI) = Total Administered Dose (µg)
Total Planned Dose (µg)
 
Time Index (TI) = Planned Treatment Duration (weeks)
Actual Treatment Duration (weeks)  
 
Planned cumulative dose for W_pro1 and cemiplimab compounds is defined as follows: 
• 
The planned dose of W_pro1 is
µg (
 µg + 
 µg + 
µg) for Cycle 1, 
µg 
µg + 
µg + 
µg) for Cycle 2, and 
µg for all following cycles. In the case 
a patient has attended 5 cycles, the planned cumulative dose for W_pro1 is 
µg, 
irrespectively if the patient has been treated at each cycle or not. 
• 
The planned dose of cemiplimab is
mg per cycle. In the case a patient has 
attended 5 cycles, the planned cumulative dose of cemiplimab is 
mg, 
irrespectively if the patient has been treated at each cycle or not. 
Planned treatment duration (weeks) for W_pro1 and cemiplimab is defined as follows: 
• 
W_pro1 and cemiplimab:  
Planned duration per cycle is 21 days.  
Planned treatment duration (weeks) = (number of cycles * 21)/7, irrespectively if the 
patient has been treated at each cycle or not.  
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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For patients who did not receive any amount of a compound, the dose exposure 
parameters for that treatment (number of cycles, duration of treatment, cumulative dose, 
dose intensity, and relative dose intensity) will be set to 0. 
Additionally, the relative dose intensity will be presented categorically (i.e., number and 
percentage of patients with relative dose intensity of < 60%, 60 - < 80%, 80 - < 90%, 90 - < 
110%, ≥ 110%). Moreover, the number and percentage of patients with any dose delay, 
with any dose modification, and any dose interruption by compound will be presented.  
All data will be listed. 
8.9.3 
Adverse events 
AEs will be coded using the MedDRA® (version 22.1 or later version) coding system to get 
a SOC and PT for each AE and will be graded for severity using NCI CTCAE v5.0.  
A TEAE is defined as any AE with an onset date on or after the first administration of IMP 
(if the AE was absent before the first administration of IMP (W_pro1 or cemiplimab, 
whichever comes first)) or worsened after the first administration of IMP (if the AE was 
present before the first administration of IMP).  
AEs with an onset date more than 30 days (after the last administration of W_pro1) or 
90 days (90 days after last administration of cemiplimab for Part 2, Arm 1A and Arm 2), 
respectively, after the last administration of W_pro1 or cemiplimab will be considered as 
treatment-emergent only if assessed as related to IMP by the investigator. TEAEs will be 
summarized overall and by treatment group for patients in the safety set. 
For patients from Arm 1B who switch to cemiplimab monotherapy, the analysis of AEs will 
be additionally performed for each IMP separately, (i.e. only TEAEs from the first dose of 
W_pro1 until last dose of W_pro1 +30 days will be reported as TEAEs for Arm 1B). 
In addition, cemiplimab TEAEs will be reported in separate AE tables using the 
subsequent cemiplimab monotherapy on progression set. Cemiplimab TEAEs are defined 
as TEAEs with an onset date on or after the first dose of cemiplimab until the last dose of 
cemiplimab +90 days. TEAEs with an onset within the 30 days after last dose of W_pro1 
but after start of first cemiplimab treatment will be counted twice, as TEAE for Arm 1B and 
as cemiplimab TEAE in the respective tables and listings. 
AEs started prior to first administration of IMP or AEs after last administration of IMP 
(follow-up AEs) will be included only in the AE listings. 
AEs related to W_pro1 
AEs related to W_pro1 are AEs with the item “Causality (relationship to W_pro1)” ticked 
“Related” in “Adverse Events” form of the eCRF. If the item is missing, the AE will be 
considered as related to W_pro1. 
 
AEs related to cemiplimab 
AEs related to cemiplimab are AEs with the item “Causality (relationship to cemiplimab)” 
ticked “Related” in “Adverse Events” form of the eCRF. If the item is missing, the AE will 
be considered as related to cemiplimab. 


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AEs related to IMP (W_pro1 + cemiplimab) 
AEs related to IMP are AEs related to either W_pro1 or cemiplimab (or both). 
 
AE leading to permanent study treatment discontinuation (any compound) 
AE leading to discontinuation are the AEs with the items “Action taken with W_pro1” or 
“Action taken with Cemiplimab” ticked “Trial treatment permanently withdrawn”. 
 
AE leading to dose reduction (any compound) 
AE leading to dose reduction are the AEs with the items “Action taken with W_pro1” or 
“Action taken with Cemiplimab” ticked “Dose reduced”. 
 
AE leading to dose delay (any compound) 
AE leading to dose delay are the AEs with the items “Action taken with W_pro1” or “Action 
taken with Cemiplimab” ticked “Trial treatment withdrawn temporarily”. 
 
AE leading to dose modification (any compound) 
AE leading to dose modification are the AEs with the items “Action taken with W_pro1” or 
“Action taken with Cemiplimab” ticked “Dose reduced” or “Trial treatment withdrawn 
temporarily”. 
 
Overall summary of treatment-emergent adverse events (TEAEs) 
The number and percentage of patients reporting at least one TEAE will be summarized 
for each of the following AE types: 
• 
Any TEAEs 
• 
TEAEs related to IMP 
• 
TEAEs related to W_pro1 
• 
TEAEs related to Cemiplimab 
• 
Grade ≥3 (Maximum intensity) TEAEs 
• 
Grade ≥3 TEAEs related to IMP 
• 
Grade ≥3 TEAEs related to W_pro1 
• 
Grade ≥3 TEAEs related to Cemiplimab 
• 
TEAEs related to trial procedure  
• 
TEAEs related to prostate cancer surgery (Part 2 Arm 2 / Arm 3) 
• 
Any Serious TEAEs 
• 
Serious TEAEs related to IMP  


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• 
Serious TEAEs related to W_pro1 
• 
Serious TEAEs related to Cemiplimab 
• 
Serious TEAEs leading to death 
• 
Serious TEAEs leading to death related to IMP 
• 
Serious TEAEs leading to death related to W_pro1 
• 
Serious TEAEs leading to death related to Cemiplimab 
• 
TEAEs leading to IMP dose modification 
• 
TEAEs leading to W_pro1 dose modification 
• 
TEAEs leading to Cemiplimab dose modification 
• 
TEAEs leading to IMP dose reduction 
• 
TEAEs leading to W_pro1 dose reduction 
• 
TEAEs leading to Cemiplimab dose reduction 
• 
TEAEs leading to IMP dose delay 
• 
TEAEs leading to W_pro1 dose delay 
• 
TEAEs leading to Cemiplimab dose delay 
• 
TEAEs leading to permanent discontinuation of IMP 
• 
TEAEs leading to permanent discontinuation of W_pro1 
• 
TEAEs leading to permanent discontinuation of Cemiplimab 
For the analysis of Part 1 of the trial, the following AE types will be added in the overall 
summary of TEAEs: 
• 
DLTs 
 
Analyses of adverse events  
The number and percentage of patients for each category above will be summarized by 
SOC and PT as per MedDRA. If a SOC / PT is reported more than once for a patient, the 
patient will only be counted once for this SOC / PT. All AE summary tables will be sorted 
by descending frequency (%) by SOC and by PT within SOC with respect to the Parts 1 
and 2 Total column. The number of events will be summarized in the same table.  
 
The following AE tables by SOC and PT will be generated: 
• 
TEAEs by System Organ Class and Preferred Term 
• 
TEAEs related to IMP by System Organ Class and Preferred Term 
• 
TEAEs related to W_pro1 by System Organ Class and Preferred Term 


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• 
TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
Grade ≥3 (Maximum intensity) TEAEs by System Organ Class and Preferred Term 
• 
Grade ≥3 TEAEs related to IMP by System Organ Class and Preferred Term 
• 
Grade ≥3 TEAEs related to W_pro1 by System Organ Class and Preferred Term 
• 
Grade ≥3 TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
TEAEs related to trial procedure by System Organ Class and Preferred Term 
• 
TEAEs related to prostate cancer surgery (Part 2 Arm 2 / Arm 3) by System Organ 
Class and Preferred Term 
• 
Any Serious TEAEs by System Organ Class and Preferred Term 
• 
Serious TEAEs related to IMP by System Organ Class and Preferred Term 
• 
Serious TEAEs related to W_pro1 by System Organ Class and Preferred Term 
• 
Serious TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
Serious TEAEs leading to death by System Organ Class and Preferred Term 
• 
Serious TEAEs leading to death related to IMP by System Organ Class and Preferred 
Term 
• 
Serious TEAEs leading to death related to W_pro1 by System Organ Class and 
Preferred Term 
• 
Serious TEAEs leading to death related to Cemiplimab by System Organ Class and 
Preferred Term 
• 
TEAEs leading to IMP dose reduction by System Organ Class and Preferred Term 
• 
TEAEs leading to W_pro1 dose reduction by System Organ Class and Preferred Term 
• 
TEAEs leading to Cemiplimab dose reduction by System Organ Class and Preferred 
Term 
• 
TEAEs leading to IMP dose delay by System Organ Class and Preferred Term 
• 
TEAEs leading to W_pro1 dose delay by System Organ Class and Preferred Term 
• 
TEAEs leading to Cemiplimab dose delay by System Organ Class and Preferred Term 
• 
TEAEs leading to IMP dose modification by System Organ Class and Preferred Term 
• 
TEAEs leading to W_pro1 dose modification by System Organ Class and Preferred 
Term 
• 
TEAEs leading to Cemiplimab dose modification by System Organ Class and 
Preferred Term 
• 
TEAEs leading to permanent discontinuation of IMP by System Organ Class and 
Preferred Term 
• 
TEAEs leading to permanent discontinuation of W_pro1 by System Organ Class and 
Preferred Term 


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• 
TEAEs leading to permanent discontinuation of Cemiplimab by System Organ Class 
and Preferred Term 
For the analysis of Part 1 of the trial, the following AE tables by SOC and PT will be 
generated: 
• 
DLTs by System Organ Class and Preferred Term 
 
In addition, the number and percentages of patients reporting the most frequent TEAEs 
(PT >= 5% in any treatment group) will be summarized by PT only.  
Similar tables to be generated for 
• 
Most frequent TEAEs (>= 5%) related to IMP by Preferred Term 
• 
Most frequent TEAEs (>= 5%) related to W_pro1 by Preferred Term 
• 
Most frequent TEAEs (>= 5%) related to Cemiplimab by Preferred Term 
TEAEs by IMP relationship: 
The number and percentages of patients with TEAEs will be summarized by relationship to 
IMP (IMP related and not IMP related) by PT nested within SOC. The worst relationship to 
IMP will be counted if a TEAE is reported more than once by the same patients for this 
SOC / PT. Same tables will be generated for TEAEs by relationship to W_pro1 (related to 
W_pro1 and not related to W_pro1) and by relationship to Cemiplimab (related to 
Cemiplimab and not related to Cemiplimab). 
TEAEs by worst NCI-CTCAE grade: 
Moreover, the number and percentage of patients with any TEAE will be summarized by 
worst NCI CTCAE grade by PT nested within SOC. Only the worst grade will be counted if 
a TEAE is reported more than once by the same patients for the SOC / PT. The same 
tables will be generated for TEAEs related to IMP by worst NCI CTCAE grade, TEAEs 
related to W_pro1 by worst NCI CTCAE grade and TEAEs related to Cemiplimab by worst 
NCI CTCAE grade. 
TEAE table per CT.gov.req: 
Moreover, the number and percentage of patients with any non-serious TEAE will be 
summarized by SOC and PT. A table for non-serious TEAE (> 3% of patients in any 
treatment arm at the PT level) will be generated . 
 
For patients from Arm 1B who switch to cemiplimab monotherapy, separate AE tables 
summarizing cemiplimab TEAEs using the safety subsequent cemiplimab monotherapy on 
progression set will be generated.  


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Overall summary of cemiplimab TEAEs 
The number and percentage of patients reporting at least one cemiplimab TEAE will be 
summarized for each of the following AE types: 
• 
Any TEAEs 
• 
TEAEs related to Cemiplimab 
• 
Grade ≥3 (Maximum intensity) TEAEs 
• 
Grade ≥3 TEAEs related to Cemiplimab 
• 
Any serious TEAEs 
• 
Serious TEAEs related to Cemiplimab 
• 
Serious TEAEs leading to death 
• 
Serious TEAEs leading to death related to Cemiplimab 
• 
TEAEs leading to Cemiplimab dose modification 
• 
TEAEs leading to Cemiplimab dose reduction 
• 
TEAEs leading to Cemiplimab dose delay 
• 
TEAEs leading to permanent discontinuation of Cemiplimab 
 
The following AE tables by SOC and PT will be generated for cemiplimab 
TEAEs: 
• 
TEAEs by System Organ Class and Preferred Term 
• 
TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
Grade ≥ 3 (Maximum intensity) TEAEs 
• 
Grade ≥ 3 TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
Any serious TEAEs by System Organ Class and Preferred Term 
• 
Serious TEAEs related to Cemiplimab by System Organ Class and Preferred Term 
• 
Serious TEAEs leading to death by System Organ Class and Preferred Term 
• 
Serious TEAEs leading to death related to Cemiplimab by System Organ Class and 
Preferred Term 
• 
TEAEs leading to Cemiplimab dose reduction by System Organ Class and Preferred 
Term 
• 
TEAEs leading to Cemiplimab dose delay by System Organ Class and Preferred Term 
• 
TEAEs leading to Cemiplimab dose modification by System Organ Class and 
Preferred Term 
• 
TEAEs leading to permanent discontinuation of Cemiplimab by System Organ Class 
and Preferred Term 


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AE listings 
All AEs will be listed. Further, all deaths, SAEs, all AEs leading to death, and AEs leading 
to permanent discontinuation of IMP (W_pro1 and/or cemiplimab) will be listed. 
Cemiplimab TEAEs in Arm 1B will be flagged in the AE listings. 
For Part 1 a listing of DLTs will be generated. 
 
 


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8.9.4 
Laboratory assessments 
Clinical laboratory data to be summarized include hematology, blood chemistry, 
coagulation, thyroid hormones and urinalysis. The clinical laboratory parameters to be 
assessed are listed in Table 8-2 and the scheduled time points for assessment are 
presented in the SoA (see Section 13.6). 
All laboratory parameters, except serology assessments, are reported in the clinical 
database using local safety laboratories. Measurements and corresponding Low and High 
ranges will be converted into Standard International (SI) units. Values outside the normal 
ranges are classified as “Not clinically significant” or “Clinically significant” by the 
investigator. 
Serology parameters are analyzed by a central laboratory. 
For the derivation of the minimum post-baseline measurement / maximum post-baseline 
measurement / or worst post-baseline toxicity CTC grades, measurements collected at 
unscheduled visits will be considered.  
The End of Study measurement is defined as last available safety assessment, either at 
Safety FU D30 or Safety FU D90 Visit (whichever occurs later) or last available safety 
assessment in case of early trial discontinuation or death. Measurements after switch to 
cemiplimab monotherapy will not be considered in the derivation of the End of Study 
measurement. 
Clinical laboratory parameters at each scheduled visit and change from baseline to each 
post-baseline time point will be summarized using descriptive summary statistics for each 
parameter by treatment group. 
The number and percentage of patients reporting markedly abnormal clinical laboratory 
values as reported by the investigator at any point on the trial will be summarized for each 
parameter by visit and treatment group using the following categories: Clinically significant 
low, Low, Normal, High, Clinically significant high.  
Shift tables from baseline to Minimum Post-baseline / Maximum Post-baseline and to End 
of Study measurement with respect to reference range values (Clinically significant low, 
Low, Normal, High, Clinically significant high) will be generated for each parameter by 
treatment group. 
Clinical laboratory results will be classified according to of NCI CTCAE v5.0. Laboratory 
results not corresponding to a NCI CTCAE term will not be graded. CTC grades for the 
respective parameters will be reported using the following categories: Grade 0, Grade 1, 
Grade 2, Grade 3, Grade 4 by visit and treatment group. Shift tables from baseline to worst 
post-baseline toxicity grade and to End of Study measurement will be provided for each 
laboratory parameter by treatment group.  
A list or laboratory parameters to be analyzed by CTC grades is available in Section 13.6. 
Urinalysis, dipstick results will be reported only by number of patients and percentage for 
each parameter by visit and treatment group.  


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Microscopic urinalysis parameters (where available), serology parameters and circulating 
tumor cells will be listed only.  
All clinical laboratory data will also be presented in the data listings. Abnormal clinical 
laboratory values and clinically significant values as reported by the investigator will be 
flagged in the listing. 
 
Table 8-2: Local Safety Laboratory Tests (Blood and Urine) - Overview 
Parameters (by group) 
Hematology: 
hemoglobin, hematocrit, red blood cell count (RBC), white blood cell count (WBC) and 
differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), platelet count 
Coagulation: 
international normalized ratio (INR), activated partial thromboplastin time, fibrinogen 
Blood chemistry: 
alkaline phosphatase (ALP), creatinine, ferritin, C-reactive protein (CRP), albumin, alanine 
aminotransferase (ALT), amylase, aspartate aminotransferase (AST), gamma glutamyl 
transpeptidase (GGT), total bilirubin, blood urea nitrogen (BUN), glucose, lipase, sodium, 
potassium, calcium 
Thyroid Hormones (only collected for Arm 1A and Arm 2) 
thyroid function (thyroid stimulating hormone [TSH], free thyroxine [fT4], free triiodothyronine 
[fT3] and total triiodothyronine [T3]) 
Urinalysis: 
Dipstick: specific gravity, pH, glucose, protein, ketones, blood  
Microscopic urinalysis: If warranted by dipstick results, urine sediment will be microscopically 
examined for presence of red blood cells, white blood cells, casts, crystals, epithelial cells, and 
bacteria 
Circulating tumor cells (optional) 
Serology (provided by a central laboratory): 
Hepatitis B Virus Core Antibody, Hepatitis B Virus Core IgM Antibody, Hepatitis B Virus Surface 
Antigen, Hepatitis B Virus Surface Antibody, Hepatitis C Virus Antibody, HIV-1/2 Antibody + HIV-
1 p24 Antigen 
The following serology parameters will be provided only in case of positive findings in the normal 
serology tests above: 
Hepatitis C Virus RNA, Hepatitis B Virus Surface Antibody (quantitative), Hepatitis B Virus e 
Antigen, Hepatitis B Virus DNA, HIV-1 p24 Antigen,  
HIV-1/2 Antibody, HIV 1 (Blot), HIV 2 (Blot), HIV-1 RNA 
 


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8.9.5 
Vital signs 
Vital sign parameters (blood pressure, pulse rate, and body temperature) and the 
scheduled visits and time points (pre-treatment or post-treatment) for assessments are 
presented in the SoA (see Section 13.6).  
Vital sign parameters at each time point and change from baseline to each post-baseline 
time point will be summarized using descriptive summary statistics for each parameter by 
treatment group. In addition, weight and BMI reported at Screening, C4 D1, EoT, Safety 
FU D30 and Safety FU D90 Visit (where applicable) will be summarized in the same way. 
The End of Study measurement is defined as last available safety assessment, either at 
Safety FU D30 or Safety FU D90 Visit (whichever occurs later) or last available safety 
assessment in case of early trial discontinuation or death. Measurements after switch to 
cemiplimab monotherapy will not be considered in the derivation of the End of Study 
measurement. 
Vital sign values for each parameter will be assigned an LNH classification according to 
whether the value is lower (L), within (N), or higher (H) the reference range for that 
parameter. The values will be summarized using shift tables from baseline to End of Study 
measurement with respect to reference range values (low, normal, high) for each 
parameter by treatment group. 
Table 8-3: Normal Ranges for Vital Signs 
Parameter 
Range  
Systolic blood pressure 
90-140 mmHg 
Diastolic blood pressure 
40-90 mmHg 
Pulse rate 
40-100 bpm 
Temperature (where applicable) 
≤ 38 °C 
 
Scatter plots will be produced for each vital signs parameter comparing baseline and End 
of Study measurement. 
All vital sign data will also be presented in the data listings, abnormal values will be flagged. 
8.9.6 
ECG 
ECGs parameters and the scheduled visits for assessment are presented in the SoA (see 
Section 13.6). 
ECGs will be judged by the investigator as normal, abnormal not clinically significant 
(NCS) or abnormal clinically significant (CS). The number and percentage of patients with 
clinically significant ECG findings will be summarized by treatment group for visit. 
Ventricular heart rate (bpm) at each visit and change from baseline to each post-baseline 
time point will be summarized using descriptive summary statistics by treatment group. 
All ECG parameters will also be presented in the data listings. 


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8.9.7 
Physical examination 
Comprehensive physical examinations will be performed at screening. During the 
treatment, the investigators should make an overall health judgement and make only in-
depth examinations if clinically indicated.  
Depending on timing (before or after signing the ICF for trial participation), the clinically 
significant findings of the physical examination have to be recorded as medical/surgical 
history or as AEs. 
The complete physical examination at screening including the following body systems: 
General Appearance, Head and Neck, Skin, Eyes, Ears, Nose & Throat, Lungs, Heart, 
Abdomen, Lymph Nodes, Musculoskeletal System (including Extremities and Spine), 
Neurological Findings, Genito-Urinary System, Anus/Rectum, and Other.  
At all visits after screening, an abbreviated physical examination will be performed. 
The abbreviated physical examination includes an overall health judgement (any new or 
worsened abnormalities since previous assessment [Y/N]) and brief interim history 
(change of symptoms). In-depth physical examinations are required if obvious pathological 
signs are visible or in the case the patient states any signs or symptoms.  
The number and percentage of patients with assessments of normal, abnormal NCS, 
abnormal CS at screening visit will be displayed in a summary table for each body system. 
For visits after Screening, the number of percentages of patients with any new or 
worsened abnormalities since previous assessment will be presented. Details regarding 
the new or worsened abnormalities will be reported in the physical examination listing. 
All physical examination data will be listed. 
8.9.8 
ECOG PS 
ECOG PS will be assessed according to the SoA (see Section 13.6).  
The following ECOG PS categories will be reported: 
GRADE 
ECOG PERFORMANCE STATUS 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities; 
up and about more than 50% of waking hours 
3 
Capable of only limited selfcare; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any selfcare; totally confined to bed or chair 


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GRADE 
ECOG PERFORMANCE STATUS 
5 
Dead 
Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the Eastern Cooperative Oncology 
Group. Am J Clin Oncol. 1982; 5: 649-655. 
Available from: https://ecog-acrin.org/resources/ecog-performance-status 
The number and percentage of patients in each ECOG PS category will be summarized by 
visit and treatment group.  
Shift tables from baseline to the D1 post baseline visits for each cycle with respect to 
ECOG PS categories by treatment group will be generated. All ECOG PS data will be 
listed. 


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9 
QUALITY CONTROL 
SAS programs are developed to produce output such as analysis data sets, summary 
tables, data listings, figures or statistical analyses. An overview of the development of 
programs is detailed in Syneos Health Developing Statistical Programs SOP (3907). 
Syneos Health Developing Statistical Programs SOP (3907), Conducting the Transfer of 
Biostatistical Deliverables SOP (3908) and the SAS Programming and Validation Plan 
(version 2.0, dated 23 APR 2021) describes the quality control procedures that are 
performed for all SAS programs and output. Quality control (QC) is defined here as the 
operational techniques and activities undertaken to verify that the SAS programs produce 
the output by checking for their logic, efficiency and commenting and by review of the 
produced output.  
 


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10 PROGRAMMING CONSIDERATIONS 
All tables, data listings, figures, and statistical analyses will be generated using SAS® for 
Windows, Release 9.4 or higher (SAS® Institute Inc., Cary, NC, USA). Computer-generated 
table, listing, and figure output will adhere to the following specifications.  
10.1 General Considerations 
• 
A separate SAS program will be created for each output. 
• 
Each output will be stored in a separate file. 
• 
Output files will be delivered in rtf format. In addition, 3 combined pdf files for tables, 
figures and listings will be delivered (combined pdf file including bookmarks). 
• 
Numbering of TFLs will follow ICH E3 guidance. 
10.2 Table, Listing, and Figure Format 
10.2.1 
General 
• 
All TFLs will be produced in A4 landscape format, unless otherwise specified. 
• 
All TFLs will be produced using the Arial font, size 9 for Header and Body. Arial font, 
size 8 in Footer.  
• 
The data displays for all TFLs will have a Top / Left / Bottom / Right:1 inch (2.54 cm), 1 
inch (2.54 cm), 0.5 inch (1.27 cm), 0.5 inch (1.27 cm) blank margin on all sides. 
• 
Headers for figures will be in Arial font, size 9, footers for figures will be in Arial font, 
size 8. 
• 
Legends will be used for all figures with more than 1 variable, group, or item displayed. 
• 
TFLs will be in black and white (no color). 
• 
Specialized text styles, such as bolding, italics, borders, shading, and superscripted 
and subscripted text, will not be used in the TFLs, unless otherwise specified. On 
some occasions, superscripts 1, 2, or 3 may be used. 
• 
Only standard keyboard characters will be used in the TFLs. Special characters, such 
as nonprintable control characters, printer-specific, or font-specific characters, will not 
be used. Hexadecimal-derived characters will be used, where possible, if they are 
appropriate to help display math symbols (e.g., μ). Certain subscripts and superscripts 
(e.g., cm2, Cmax) will be employed on a case-by-case basis. 
• 
Mixed case will be used for all titles, footnotes, column headers, and programmer 
supplied formats, as appropriate. 
10.2.2 
Headers 
• All output should have the following header at the top left of each page: 
• BioNTech SE Protocol: RN5609C00 


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• Draft/Final Run <date> 
• All output should have Page n of N at the top or bottom right corner of each page. 
TFLs are internally paginated in relation to the total length (i.e., the page number 
should appear sequentially as page n of N, where N is the total number of pages in 
the table). 
• The date output was generated should appear along with the program name as a 
footer on each page. 
10.2.3 
Display Titles 
• Each TFL are identified by the designation and a numeral. (i.e., Table 14.1.1). ICH 
E3 numbering will be applied for the current trial. A decimal system (x.y and x.y.z) 
are used to identify TFLs with related contents. The title is centered. The analysis set 
are identified on the line immediately following the title. The title and table 
designation are single spaced. A solid line spanning the margins will separate the 
display titles from the Column headers. There will be 1 blank line between the last 
title and the solid line. 
Table x.y.z: First Line of Title 
Second Line of Title if Needed - ITT Set 
 
10.2.4 
Column Headers 
• Column headings are displayed immediately below the solid line described above in 
initial upper-case characters.  
• For numeric variables, include “unit” in column or row heading when appropriate. 
• Analysis set sizes will be presented for each treatment group in the column heading 
as (N=xx) (or in the row headings, if applicable). This is distinct from the “n” used for 
the descriptive statistics representing the number of patients in the analysis set. 
• The order of treatments in the tables and listings will Active comparators first, 
followed by a total column (if applicable). 
10.2.5 
Body of the Data Display 
10.2.5.1 
General Conventions 
Data in columns of a table or listing are formatted as follows: 
• Alphanumeric values are left-justified; 


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• Whole numbers (e.g., counts) are center-justified; and 
• Numbers containing fractional portions are center-justified. 
10.2.5.2 
Table Conventions 
• Units will be included where available 
• If the categories of a parameter are ordered, then all categories between the 
maximum and minimum category are presented in the table, even if n=0 for all 
treatment groups in a given category that is between the minimum and maximum 
level for that parameter. For example, the frequency distribution for symptom severity 
would appear as: 
Severity 
Rating 
n 
Mild  
0 
Moderate 
8 
Severe 
3 
 
• Where percentages are presented in these tables, zero percentages will not be 
presented and so counts of 0 will be presented as 0 and not as 0 (0%). 
• If the categories are not ordered (e.g., Medical History, Reasons for Discontinuation 
from the Trial, etc.), then only those categories for which there is at least 1 patient 
represented in 1 or more groups are included. 
• Unless otherwise specified, the estimated mean and median for a set of values are 
printed out to 1 more significant digit than the original values, and standard 
deviations are printed out to 2 more significant digits than the original values. The 
minimum and maximum should report the same significant digits as the original 
values. For example, for systolic blood pressure: 
n 
XX 
Mean 
XXX.X 
Std Dev 
X.XX 
Median 
XXX.X 
Minimum 
XXX 
Maximum 
XXX 
 


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• P-values are output in the format: “0.xxx”, where xxx is the value rounded to 3 
decimal places. Every p-value less than 0.001 will be presented as <0.001. If the p-
value is returned as >0.999, then present as >0.999. 
• Percentage values are printed to one decimal place, in parentheses with no spaces, 
one space after the count (e.g., 7 (12.8%), 13 (5.4%)). Unless otherwise noted, for all 
percentages, the number of patients in the analysis set for the treatment group who 
have an observation will be the denominator. Percentages after zero counts should 
not be displayed and percentages equating to 100% are presented as 100%, without 
decimal places.  
• The percentage of patients is normally calculated as a proportion of the number of 
patients assessed in the relevant treatment group (or overall) for the analysis set 
presented. However, careful consideration is required in many instances due to the 
complicated nature of selecting the denominator, usually the appropriate number of 
patients exposed. Describe details of this in footnotes or programming notes. 
• For categorical summaries (number and percentage of patients) where a patient can 
be included in more than one category, describe in a footnote or programming note if 
the patient are included in the summary statistics for all relevant categories or just 1 
category and the criteria for selecting the criteria. 
10.2.5.3 
Listing Conventions 
• Listings will be sorted for presentation in order of treatment groups as above, patient 
number, visit/collection day, and visit/collection time. 
• Dates are printed in SAS DATE9.format (“ddMMMyyyy”: 01JUL2000). Missing 
portions of dates are represented on patient listings as dashes (--JUL2000).  
• All observed time values are to be presented using a 24-hour clock HH:MM or 
HH:MM:SS format (e.g., 11:26:45, or 11:26). Time will only be reported if it was 
measured as part of the trial. 
• Units will be included where available 
10.2.5.4 
Figure Conventions 
• Unless otherwise specified, for all figures, trial visits will be displayed on the X-axis 
and endpoint (e.g., treatment mean change from Baseline) values will be displayed 
on the Y-axis. 


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10.2.6 
Footnotes 
• A solid line spanning the margins will separate the body of the data display from the 
footnotes.  
• All footnotes will be left justified with single-line spacing immediately below the solid 
line underneath the data display. 
• Patient specific footnotes are avoided, where possible. 
• Footnotes will be used sparingly and add value to the table, figure, or listing. If more 
than six lines of footnotes are planned, then a cover page is strongly recommended 
to be used to display footnotes, and only those essential to comprehension of the 
data will be repeated on each page.  
• The last line of the footnote section will be a standard source line that indicates the 
name of the program used to produce the data display, date the program was run, 
(i.e., Program name: myprogram; Run Date/time: ddmmmyyyy hh:mm). 


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11 TABLE OF CONTENTS FOR TABLES, FIGURES AND LISTINGS 
This section contains lists of the summary table, figures and listings tentatively planned for 
this trial. Changes in the number or content of planned TFLs are not considered deviations 
from this SAP. 
The TFLs to be generated for the Interim Analysis are flagged with a “Yes” in the 
corresponding columns in the sections below. 
The decision which TFLs to be generated for the Follow-up Analysis will be specified after 
the main analysis is available. 
11.1.1 
Tables 
Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
14. 
 
TABLES  
 
 
14.1 
 
Demographic Data 
 
 
 
 
 
 
 
14.1.1 
 
Patient Disposition 
 
 
 
14.1.1.1 
Screening failures 
Screened set 
 
 
14.1.1.2 
Analysis sets   
Screened set 
Yes 
 
14.1.1.3 
Enrollment by site 
Screened set 
 
 
14.1.1.4 
Patient disposition 
ITT set 
Yes 
 
 
 
 
 
14.1.2 
 
Protocol Deviations 
 
 
 
14.1.2.1 
Important protocol deviations   
ITT set 
 
 
14.1.2.2 
Important protocol deviations due to COVID-19   
ITT set 
 
 
 
 
 
 
14.1.3 
 
Demographic and Baseline Characteristics 
 
 
14.1.3.1 
 
Patient Demographic and Baseline 
Characteristics 
 
 
 
14.1.3.1.1 
Demographic and baseline characteristics   
mITT set 
Yes 
 
14.1.3.1.2 
Demographic and baseline characteristics 
(optional)  
Safety set 
 
 
14.1.3.1.3 
Demographic and baseline characteristics 
(optional) 
ITT set 
 
 
14.1.3.1.4 
Demographic and baseline characteristics 
(optional) 
PP set 
 
 
 
 
 
 
14.1.3.2 
 
Baseline Disease Characteristics 
 
 
 
14.1.3.2.1 
Disease characteristics 
mITT set 
Yes 
 
14.1.3.2.2 
Disease characteristics – TNM Stage 
mITT set 
Yes 
 
14.1.3.2.3 
Disease characteristics –  Imaging (PCWG3) 
mITT set 
Yes 
 
14.1.3.2.4 
Prior therapy lines 
mITT set 
Yes 
 
14.1.3.2.5 
Prior therapy types 
mITT set 
 
 
14.1.3.2.6 
Prior cancer surgeries 
mITT set 
 
 
14.1.3.2.7 
Prior systemic cancer therapies 
mITT set 
 
 
 
 
 
 
14.1.4 
 
Medications 
 
 
 
14.1.4.1.1 
Prior medications 
mITT set 
 
 
14.1.4.1.2 
Concomitant medications 
mITT set 
 
 
 
 
 
 
 
 
Medical History 
 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.1.4.2.1 
Prior medical history 
mITT set 
 
 
14.1.4.2.2 
Concomitant diseases 
mITT set 
 
 
 
 
 
 
14.1.5 
 
Other Procedures 
 
 
 
14.1.5.1 
Cancer radiotherapies 
mITT set 
 
 
14.1.5.2 
Procedures and non-drug therapies 
mITT set 
 
 
 
 
 
 
14.1.6 
 
Exposure 
 
 
 
14.1.6.1 
Exposure to IMP/NIMP: Number of cycles 
Safety set 
Yes 
 
14.1.6.2 
Exposure to IMP/NIMP: Dose intensities 
Safety set 
Yes 
 
14.1.6.3 
Exposure to IMP/NIMP: Dose delays, reductions 
and interruptions 
Safety set 
Yes 
 
 
 
 
 
14.2 
 
Efficacy Data 
 
 
14.2.1 
 
Primary Efficacy Parameter Objective Response 
Rate 
 
 
 
14.2.1.1.1 
Objective Response Rate (ORR) based on 
PCWG3 
mITT set 
Yes 
 
14.2.1.1.1a 
Objective Response Rate (ORR) based on 
PCWG3, SAS output 
mITT set 
 
 
14.2.1.1.2 
Objective Response Rate (ORR) based on 
PCWG3 
ITT set 
Yes 
 
14.2.1.1.2a 
Objective Response Rate (ORR) based on 
PCWG3, SAS output 
ITT set 
 
 
14.2.1.1.3 
Objective Response Rate (ORR) based on 
PCWG3 
PP set 
 
 
14.2.1.1.3a 
Objective Response Rate (ORR) based on 
PCWG3, SAS output 
PP set 
 
 
 
 
 
 
 
 
Subgroup Analyses 
 
 
 
14.2.1.1.1.1 
Objective Response Rate (ORR) based on 
PCWG3 by age category 
mITT set 
 
 
14.2.1.1.1.1a 
Objective Response Rate (ORR) based on 
PCWG3 by age category, SAS output 
mITT set 
 
 
14.2.1.1.1.2 
Objective Response Rate (ORR) based on 
PCWG3 by subgroup 2 
mITT set 
 
 
14.2.1.1.1.2a 
Objective Response Rate (ORR) based on 
PCWG3 by subgroup 2, SAS output 
mITT set 
 
 
 
 
 
 
 
14.2.1.1.4 
Objective Response Rate (ORR) based on 
Radiological Soft Tissue Evaluation per 
Investigator 
mITT set 
Yes 
 
14.2.1.1.5 
Clinical Progression 
mITT set 
Yes 
 
 
 
 
 
14.2.2 
 
Secondary Efficacy Parameters 
 
 
14.2.2.1 
 
Secondary Efficacy Parameter 1: 
PSA decline 
 
 
 
14.2.2.1.1 
PSA decline for each visit compared to baseline 
(including all PSA data as reported) 
mITT set 
 
 
14.2.2.1.2 
PSA decline for each visit  compared to 
baseline (including all PSA data as reported) 
(optional)  
ITT set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.2.2.1.3 
PSA decline for each visit  compared to 
baseline (including all PSA data as reported) 
(optional) 
PP set 
 
 
 
 
 
 
 
14.2.2.2 
Best PSA decline compared to baseline 
mITT set 
Yes 
 
 
 
 
 
Figure  
14.2.2.2.1 
PSA decline (Categorization 1): Bar Chart for 
each visit compared to baseline (including all 
PSA data as reported)– mITT set – mCRPC 
patients 
mITT set 
 
Figure  
14.2.2.2.2 
PSA decline (Categorization 1): Bar Chart for 
each visit compared to baseline (including all 
PSA data as reported)– mITT set – LPC 
patients 
mITT set 
 
Figure  
14.2.2.2.3 
PSA decline (Categorization 2): Bar Chart for 
each visit compared to baseline (including all 
PSA data as reported)– mITT set – mCRPC 
patients 
mITT set 
 
Figure  
14.2.2.2.4 
PSA decline (Categorization 2): Bar Chart for 
each visit compared to baseline (including all 
PSA data as reported)– mITT set – LPC 
patients 
mITT set 
 
 
 
 
 
 
 
14.2.2.3.1 
PSA decline: Summary by visit and percentage 
change from baseline (including all PSA data as 
reported) 
mITT set 
 
 
14.2.2.3.2 
PSA decline: Summary by visit and percentage 
change from baseline (including all PSA data as 
reported) (optional) 
ITT set 
 
 
14.2.2.3.3 
PSA decline: Summary by visit and percentage 
change from baseline (including all PSA data as 
reported) (optional) 
PP set 
 
 
 
 
 
 
Figure 
14.2.2.4.1 
PSA decline: Waterfall plot of maximum decline 
from baseline – mITT set – mCRPC patients 
mITT set 
 
Figure 
14.2.2.4.2 
PSA decline: Waterfall plot of maximum decline 
from baseline – mITT set – LPC patients 
mITT set 
 
Figure 
14.2.2.4.3 
PSA decline: Waterfall plot of maximum decline 
from baseline – ITT set – mCRPC patients 
(optional) 
ITT set 
 
Figure 
14.2.2.4.4 
PSA decline: Waterfall plot of maximum decline 
from baseline – ITT set – LPC patients 
(optional) 
ITT set 
 
Figure 
14.2.2.4.5 
PSA decline: Waterfall plot of maximum decline 
from baseline – PP set – mCRPC patients 
(optional) 
PP set 
 
Figure 
14.2.2.4.6 
PSA decline: Waterfall plot of maximum decline 
from baseline – PP set set – LPC patients 
(optional) 
PP set 
 
 
 
 
 
 
 
14.2.2.5.1 
PSA response per PCWG3 criteria (including all 
PSA data as reported) 
mITT set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.2.2.5.2 
PSA response per PCWG3 criteria (including all 
PSA data as reported) (optional) 
ITT set 
 
 
14.2.2.5.3 
PSA response per PCWG3 criteria (including all 
PSA data as reported) (optional) 
PP set 
 
 
 
 
 
 
 
14.2.2.5.4 
Objective Response Rate (ORR) based on PSA 
per PCWG3 Criteria 
mITT set 
Yes 
 
 
 
 
 
 
 
Secondary Efficacy Parameter 2: 
PSA doubling time 
 
 
 
14.2.2.6.1 
PSA doubling time (PSADT) 
mITT set 
 
 
14.2.2.6.2 
PSA doubling time (PSADT) (optional) 
ITT set 
 
 
14.2.2.6.3 
PSA doubling time (PSADT) (optional) 
PP set 
 
 
 
 
 
 
 
 
Secondary Efficacy Parameter 3: 
Tumor response post-treatment compared to 
baseline 
 
 
 
14.2.2.7.1 
Tumor assessment post-treatment compared to 
baseline based on Radiological Soft Tissue 
Evaluation per Investigator 
mITT set 
 
 
14.2.2.7.2 
Tumor assessment post-treatment compared to 
baseline based on Radiological Soft Tissue 
Evaluation per Investigator (optional) 
ITT set 
 
 
14.2.2.7.3 
Tumor assessmente post-treatment compared 
to baseline based on Radiological Soft Tissue 
Evaluation per Investigator (optional) 
PP set 
 
 
 
 
 
 
14.2.3 
 
Exploratory Efficacy Parameters 
 
 
 
14.2.3.1.1 
Objective Response Rate (ORR) based on 
iRECIST (central reading) 
mITT set 
 
 
14.2.3.1.2 
Objective Response Rate (ORR) based on 
iRECIST (central reading) (optional) 
ITT set 
 
 
14.2.3.1.3 
Objective Response Rate (ORR) based on 
iRECIST (central reading) (optional) 
PP set 
 
 
 
 
 
 
 
14.2.3.2.1 
Duration of Response (DoR) based on PCWG3 
mITT set 
Yes 
 
14.2.3.2.1a 
Duration of Response (DoR) based on PCWG3, 
SAS output 
mITT set 
Yes 
Figure 
14.2.3.2.2 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 - mCRPC patients 
mITT set 
Yes 
 
14.2.3.2.3 
Duration of Response (DoR) based on PCWG3 
(optional) 
ITT set 
Yes 
 
14.2.3.2.3a 
Duration of Response (DoR) based on PCWG3, 
SAS output (optional) 
ITT set 
Yes 
Figure 
14.2.3.2.4 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 - mCRPC patients 
(optional) 
ITT set 
Yes 
 
14.2.3.2.5 
Duration of Response (DoR) based on PCWG3 
(optional) 
PP set 
 
 
14.2.3.2.5a 
Duration of Response (DoR) based on PCWG3, 
SAS output (optional) 
PP set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
Figure 
14.2.3.2.6 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 - mCRPC patients 
(optional) 
PP set 
 
 
 
 
 
 
 
 
Subgroup Analyses 
 
 
 
14.2.3.2.2.1 
Duration of Response (DoR) based on PCWG3 
by age category 
mITT set 
 
 
14.2.3.2.2.1a 
Duration of Response (DoR) based on PCWG3 
by age category, SAS output 
mITT set 
 
Figure 
14.2.3.2.2.2 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 - mCRPC patients by 
age category 
mITT set 
 
 
14.2.3.2.2.3 
Duration of Response (DoR) based on PCWG3 
by subgroup 2 
mITT set 
 
 
14.2.3.2.2.3a 
Duration of Response (DoR) based on PCWG3 
by subgroup 2, SAS output 
mITT set 
 
Figure 
14.2.3.2.2.4 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 - mCRPC patients by 
subgroup 2 
mITT set 
 
 
 
 
 
 
 
14.2.3.3.1 
Duration of Response (DoR) based on iRECIST 
(central reading) 
mITT set 
 
 
14.2.3.3.1a 
Duration of Response (DoR) based on iRECIST 
(central reading), SAS output 
mITT set 
 
Figure 
14.2.3.3.2 
Kaplan-Meier curve of Duration of Response 
(DoR) based on iRECIST (central reading) - 
mCRPC patients 
mITT set 
 
 
14.2.3.3.3 
Duration of Response (DoR) based on iRECIST 
(central reading) (optional) 
ITT set 
 
 
14.2.3.3.3a 
Duration of Response (DoR) based on iRECIST 
(central reading), SAS output (optional) 
ITT set 
 
Figure 
14.2.3.3.4 
Kaplan-Meier curve of Duration of Response 
(DoR) based on iRECIST (central reading) - 
mCRPC patients (optional) 
ITT set 
 
 
14.2.3.3.5 
Duration of Response (DoR) based on iRECIST 
(central reading) (optional) 
PP set 
 
 
14.2.3.3.5a 
Duration of Response (DoR) based on iRECIST 
(central reading), SAS output (optional) 
PP set 
 
Figure 
14.2.3.3.6 
Kaplan-Meier curve of Duration of Response 
(DoR) based on iRECIST (central reading) - 
mCRPC patients (optional) 
PP set 
 
 
 
 
 
 
 
14.2.3.4.1 
Progression-free Survival (PFS) based on 
PCWG3 
mITT set 
Yes 
 
14.2.3.4.1a 
Progression-free Survival (PFS) based on 
PCWG3, SAS output 
mITT set 
Yes 
Figure 
14.2.3.4.2 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 - mCRPC 
patients 
mITT set 
Yes 
Figure 
14.2.3.4.3 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 - LPC patients 
mITT set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.2.3.4.4 
Progression-free Survival (PFS) based on 
PCWG3 (optional) 
ITT set 
Yes 
 
14.2.3.4.4a 
Progression-free Survival (PFS) based on 
PCWG3, SAS output (optional)  
ITT set 
Yes 
Figure 
14.2.3.4.5 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 - mCRPC 
patients (optional) 
ITT set 
Yes 
Figure 
14.2.3.4.6 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 - LPC patients 
(optional) 
ITT set 
 
 
14.2.3.4.7 
Progression-free Survival (PFS) based on 
PCWG3 (optional) 
PP set 
 
 
14.2.3.4.7a 
Progression-free Survival (PFS) based on 
PCWG3, SAS output (optional) 
PP set 
 
Figure 
14.2.3.4.8 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 – mCRPC 
patients (optional) 
PP set 
 
Figure 
14.2.3.4.9 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 – LPC 
patients (optional) 
PP set 
 
 
 
 
 
 
 
 
Subgroup Analyses 
 
 
 
14.2.3.4.3.1 
Progression-free Survival (PFS) based on 
PCWG3 by age category 
mITT set 
 
 
14.2.3.4.3.1a 
Progression-free Survival (PFS) based on 
PCWG3 by age category, SAS output 
mITT set 
 
Figure 
14.2.3.4.3.2 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 by age 
category - mCRPC patients 
mITT set 
 
Figure 
14.2.3.4.3.3 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 by age 
category - LPC patients 
mITT set 
 
 
14.2.3.4.3.4 
Progression-free Survival (PFS) based on 
PCWG3 by subgroup 2 
mITT set 
 
 
14.2.3.4.3.4a 
Progression-free Survival (PFS) based on 
PCWG3 by subgroup 2, SAS output 
mITT set 
 
Figure 
14.2.3.4.3.5 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 by subgroup 2 
- mCRPC patients 
mITT set 
 
Figure 
14.2.3.4.3.6 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 by subgroup 2 
- LPC patients 
mITT set 
 
 
 
 
 
 
 
14.2.3.5.1 
Progression-free Survival (PFS) based on 
iRECIST (central reading) 
mITT set 
 
 
14.2.3.5.1a 
Progression-free Survival (PFS) based on 
iRECIST (central reading), SAS output 
mITT set 
 
Figure 
14.2.3.5.2 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on iRECIST (central 
reading) – mCRPC patients 
mITT set 
 
 
14.2.3.5.3 
Progression-free Survival (PFS) based on 
iRECIST (central reading) (optional) 
ITT set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.2.3.5.3a 
Progression-free Survival (PFS) based on 
iRECIST (central reading), SAS output 
(optional)  
ITT set 
 
Figure 
14.2.3.5.4 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on iRECIST (central 
reading) – mCRPC patients (optional) 
ITT set 
 
 
14.2.3.5.5 
Progression-free Survival (PFS) based on 
iRECIST (central reading) (optional) 
PP set 
 
 
14.2.3.5.5a 
Progression-free Survival (PFS) based on 
iRECIST (central reading), SAS output 
(optional) 
PP set 
 
Figure 
14.2.3.5.6 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on iRECIST (central 
reading) – mCRPC patients (optional) 
PP set 
 
 
 
 
 
 
 
14.2.3.6.1 
Overall Survival (OS) 
mITT set 
 
 
14.2.3.6.1a 
Overall Survival (OS) SAS output 
mITT set 
 
Figure 
14.2.3.6.2 
Kaplan-Meier curve for Overall Survival (OS) – 
mCRPC patients 
mITT set 
 
Figure 
14.2.3.6.3 
Kaplan-Meier curve for Overall Survival (OS) – 
LPC patients 
mITT set 
 
 
14.2.3.6.4 
Overall Survival (OS) (optional) 
ITT set 
 
 
14.2.3.6.4a 
Overall Survival (OS) SAS output (optional) 
ITT set 
 
Figure 
14.2.3.6.5 
Kaplan-Meier curve for Overall Survival (OS) – 
mCRPC patients (optional) 
ITT set 
 
Figure 
14.2.3.6.6 
Kaplan-Meier curve for Overall Survival (OS) – 
LPC patients (optional) 
ITT set 
 
 
 
 
 
 
 
14.2.3.6.7 
Overall Survival (OS) (optional) 
PP set 
 
 
14.2.3.6.7a 
Overall Survival (OS) SAS output (optional) 
PP set 
 
Figure 
14.2.3.6.8 
Kaplan-Meier curve for Overall Survival (OS) 
mCRPC patients (optional) 
PP set 
 
Figure 
14.2.3.6.9 
Kaplan-Meier curve for Overall Survival (OS) 
LPC patients (optional) 
PP set 
 
 
 
 
 
 
14.2.4 
 
Exploratory Efficacy Parameters for patients in 
Arm 1B who are treated with cemiplimab 
Monotherapy 
 
 
 
14.2.4.1.1 
Objective Response Rate (ORR) based on 
PCWG3 
Cemi Mono 
on PD set 
 
 
14.2.4.1.2 
Objective Response Rate (ORR) based on 
iRECIST (central reading) 
Cemi Mono 
on PD set 
 
 
 
 
 
 
 
14.2.4.1.3 
Duration of Response (DoR) based on PCWG3 
Cemi Mono 
on PD set 
 
 
14.2.4.1.3a 
Duration of Response (DoR) based on PCWG3, 
SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.4 
Kaplan-Meier curve of Duration of Response 
(DoR) based on PCWG3 
Cemi Mono 
on PD set 
 
 
 
 
 
 
 
14.2.4.1.5 
Duration of Response (DoR) based on iRECIST 
(central reading) 
Cemi Mono 
on PD set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.2.4.1.5a 
Duration of Response (DoR) based on iRECIST 
(central reading), SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.6 
Kaplan-Meier curve of Duration of Response 
(DoR) based on iRECIST (central reading) 
Cemi Mono 
on PD set 
 
 
 
 
 
 
 
14.2.4.1.7 
Progression-free Survival (PFS) based on 
PCWG3 
Cemi Mono 
on PD set 
 
 
14.2.4.1.7a 
Progression-free Survival (PFS) based on 
PCWG3, SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.8 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on PCWG3 
Cemi Mono 
on PD set 
 
 
 
 
 
 
 
14.2.4.1.9 
Progression-free Survival (PFS) based on 
iRECIST (central reading) 
Cemi Mono 
on PD set 
 
 
14.2.4.1.9a 
Progression-free Survival (PFS) based on 
iRECIST (central reading), SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.10 
Kaplan-Meier curve for Progression-free 
Survival (PFS) based on iRECIST (central 
reading) 
Cemi Mono 
on PD set 
 
 
14.2.4.1.11 
Progression-free Survival 2 (PFS2) based on 
PCWG3 
Cemi Mono 
on PD set 
 
 
14.2.4.1.11a 
Progression-free Survival 2 (PFS2) based on 
PCWG3, SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.12 
Kaplan-Meier curve for Progression-free 
Survival 2 (PFS2) based on PCWG3 
Cemi Mono 
on PD set 
 
 
 
 
 
 
 
14.2.4.1.13 
Overall Survival (OS) 
Cemi Mono 
on PD set 
 
 
14.2.4.1.13a 
Overall Survival (OS) SAS output 
Cemi Mono 
on PD set 
 
Figure 
14.2.4.1.14 
Kaplan-Meier curve for Overall Survival (OS) 
Cemi Mono 
on PD set 
 
 
 
 
 
 
14.2.5 
 
Further Efficacy Analyses 
 
 
 
14.2.5.1.1 
Disease status during Survival Follow-up Period 
mITT set 
 
 
14.2.5.1.2 
Biochemical recurrence after radical 
prostatectomy – post-treatment PSA values 
mITT set 
 
 
14.2.5.1.3 
Time from treatment start to post-treatment 
prostatectomy – LPC patients 
mITT set 
 
 
 
 
 
 
14.3 
 
Safety Data 
 
 
14.3.1 
 
Displays of Adverse Events 
 
 
 
14.3.1.1 
Summary of adverse events 
Safety set 
Yes 
 
14.3.1.2 
Number (%) of patients with TEAEs by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.3 
Number (%) of patients with TEAEs related to 
IMP by system organ class and preferred term 
Safety set 
Yes 
 
14.3.1.4 
Number (%) of patients with TEAEs related to 
W_pro1 by system organ class and preferred 
term 
Safety set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.3.1.5 
Number (%) of patients with TEAEs related to 
Cemiplimab by system organ class and 
preferred term 
Safety set 
 
 
14.3.1.6 
Number (%) of patients with maximum intensity 
grade >= 3 TEAEs by system organ class and 
preferred term 
Safety set 
Yes 
 
14.3.1.7 
Number (%) of patients with maximum intensity 
grade >= 3 TEAEs related to IMP by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.8 
Number (%) of patients with maximum intensity 
grade >= 3 TEAEs related to W_pro1 by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.9 
Number (%) of patients with maximum intensity 
grade >= 3 TEAEs related to Cemiplimab by 
system organ class and preferred term 
Safety set 
Yes 
 
14.3.1.10 
Number (%) of patients with TEAEs related to 
trial procedure by system organ class and 
preferred term 
Safety set 
 
 
14.3.1.11 
Number (%) of patients with TEAEs related to 
prostate cancer surgery by system organ class 
and preferred term 
Safety set 
 
 
14.3.1.12 
Number (%) of patients with serious TEAEs by 
system organ class and preferred term 
Safety set 
Yes 
 
14.3.1.13 
Number (%) of patients with serious TEAEs 
related to IMP by system organ class and 
preferred term 
Safety set 
Yes 
 
14.3.1.14 
Number (%) of patients with serious TEAEs 
related to W_pro1 by system organ class and 
preferred term 
Safety set 
Yes 
 
14.3.1.15 
Number (%) of patients with serious TEAEs 
related to Cemiplimab by system organ class 
and preferred term 
Safety set 
Yes 
 
14.3.1.16 
Number (%) of patients with serious TEAEs 
leading to death by system organ class and 
preferred term 
Safety set 
Yes 
 
14.3.1.17 
Number (%) of patients with serious TEAEs 
leading to death related to IMP by system organ 
class and preferred term 
Safety set 
 
 
14.3.1.18 
Number (%) of patients with serious TEAEs 
leading to death related to W_pro1 by system 
organ class and preferred term 
Safety set 
 
 
14.3.1.19 
Number (%) of patients with serious TEAEs 
leading to death related to Cemiplimab by 
system organ class and preferred term 
Safety set 
 
 
14.3.1.20 
Number (%) of patients with TEAEs leading to 
IMP dose reduction by system organ class and 
preferred term 
Safety set 
 
 
14.3.1.21 
Number (%) of patients with TEAEs leading to 
W_pro1 dose reduction by system organ class 
and preferred term 
Safety set 
 
 
14.3.1.22 
Number (%) of patients with TEAEs leading to 
Cemiplimab dose reduction by system organ 
class and preferred term 
Safety set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.3.1.23 
Number (%) of patients with TEAEs leading to 
IMP dose delay by system organ class and 
preferred term 
Safety set 
 
 
14.3.1.24 
Number (%) of patients with TEAEs leading to 
W_pro1 dose delay by system organ class and 
preferred term 
Safety set 
 
 
14.3.1.25 
Number (%) of patients with TEAEs leading to 
Cemiplimab dose delay by system organ class 
and preferred term 
Safety set 
 
 
14.3.1.26 
Number (%) of patients with TEAEs leading to 
permanent discontinuation of IMP by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.27 
Number (%) of patients with TEAEs leading to 
permanent discontinuation of W_pro1 by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.28 
Number (%) of patients with TEAEs leading to 
permanent discontinuation of Cemiplimab by 
system organ class and preferred term 
Safety set 
Yes 
 
14.3.1.29 
Number (%) of patients with DLTs by system 
organ class and preferred term 
Safety set 
Yes 
 
14.3.1.30 
Number (%) of patients with most frequent 
TEAEs (>= 5%) by preferred term 
Safety set 
Yes 
 
14.3.1.30.1 
Number (%) of patients with most frequent 
TEAEs (>= 5%) related to IMP by preferred term 
Safety set 
 
 
14.3.1.30.2 
Number (%) of patients with most frequent 
TEAEs (>= 5%) related to W_pro1 by preferred 
term 
Safety set 
 
 
14.3.1.30.3 
Number (%) of patients with most frequent 
TEAEs (>= 5%) related to Cemiplimab by 
preferred term 
Safety set 
 
 
14.3.1.31 
Number (%) of patients with TEAEs by system 
organ class, preferred term and worst IMP 
relationship 
Safety set 
 
 
14.3.1.32 
Number (%) of patients with TEAEs by system 
organ class, preferred term and worst 
relationship to W_pro1 
Safety set 
 
 
14.3.1.33 
Number (%) of patients with TEAEs by system 
organ class, preferred term and worst 
relationship to Cemiplimab 
Safety set 
 
 
14.3.1.34 
Number (%) of patients with TEAEs by system 
organ class, preferred term and worst NCI 
CTAE grade 
Safety set 
 
 
14.3.1.35 
Number (%) of patients with TEAEs related to 
IMP by system organ class, preferred term and 
worst NCI CTAE grade 
Safety set 
 
 
14.3.1.36 
Number (%) of patients with TEAEs related to 
W_pro1 by system organ class, preferred term 
and worst NCI CTAE grade 
Safety set 
 
 
14.3.1.37 
Number (%) of patients with TEAEs related to 
Cemiplimab by system organ class, preferred 
term and worst NCI CTAE grade 
Safety set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.3.1.38 
Number (%) of patients with non-serious TEAEs 
(>3% at preferred term level) by system organ 
class and preferred term 
Safety set 
 
 
 
 
 
 
 
14.3.1.39 
Number (%) of patients with TEAEs leading to 
IMP dose modification by system organ class 
and preferred term 
Safety set 
 
 
14.3.1.40 
Number (%) of patients with TEAEs leading to 
W_pro1 dose modification by system organ 
class and preferred term 
Safety set 
 
 
14.3.1.41 
Number (%) of patients with TEAEs leading to 
Cemiplimab dose modification by system organ 
class and preferred term 
Safety set 
 
 
 
 
 
 
 
 
Cemiplimab TEAEs 
 
 
 
14.3.1.42 
Summary of cemiplimab TEAEs 
Cemi Mono 
on PD set 
 
 
14.3.1.43 
Number (%) of patients with cemiplimab TEAEs 
by system organ class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.44 
Number (%) of patients with cemiplimab TEAEs 
related to Cemiplimab by system organ class 
and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.45 
Number (%) of patients with grade >= 3 
cemiplimab TEAEs by system organ class and 
preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.46 
Number (%) of patients with grade >= 3 
cemiplimab TEAEs related to Cemiplimab by 
system organ class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.47 
Number (%) of patients with serious cemiplimab 
TEAEs by system organ class and preferred 
term 
Cemi Mono 
on PD set 
 
 
14.3.1.48 
Number (%) of patients with serious cemiplimab 
TEAEs related to Cemiplimab by system organ 
class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.49 
Number (%) of patients with serious cemiplimab 
TEAEs leading to death by system organ class 
and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.50 
Number (%) of patients with serious cemiplimab 
TEAEs leading to death related to Cemiplimab 
by system organ class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.51 
Number (%) of patients with cemiplimab TEAEs 
leading to Cemiplimab dose reduction by 
system organ class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.52 
Number (%) of patients with cemiplimab TEAEs 
leading to Cemiplimab dose delay by system 
organ class and preferred term 
Cemi Mono 
on PD set 
 
 
14.3.1.53 
Number (%) of patients with cemiplimab TEAEs 
leading to Cemiplimab dose modification by 
system organ class and preferred term 
Cemi Mono 
on PD set 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.3.1.54 
Number (%) of patients with cemiplimab TEAEs 
leading to permanent discontinuation of 
cemiplimab by system organ class and 
preferred term 
Cemi Mono 
on PD set 
 
 
 
 
 
 
14.3.2 
 
Listings of Deaths, Other Serious and Certain 
Other Significant Adverse Events 
Safety set 
 
 
14.3.2.1 
Deaths, Listing 
Safety set 
Yes 
 
14.3.2.2 
Serious Adverse Events, Listing 
Safety set 
Yes 
 
14.3.2.3 
Treatment emergent Adverse Events leading to 
permanent discontinuation of IMP, Listing 
Safety set 
Yes 
 
14.3.2.4 
Dose-limiting toxicities (Part 1), Listing 
Safety set 
 
 
 
 
 
 
14.3.3 
Not to be 
used for any 
Tables 
Narratives of Deaths, Other Serious and Certain 
Other Significant Adverse Events 
(NOTE: this section is for Medical Writing 
narratives only, normally not completed by 
Syneos Health Biostatistics. No tables should 
go here. Nevertheless, the section is kept and a 
note should indicate the responsible party). 
 
 
 
 
 
 
 
14.3.4 
 
Laboratory, Vital Signs, and Physical 
Examination Changes  
 
 
14.3.4.1 
 
Clinical Laboratory Data 
 
 
14.3.4.1.1 
 
Hematology Data 
 
 
 
14.3.4.1.1.1 
Hematology: Summary by visit and change from 
baseline 
Safety set 
 
 
14.3.4.1.1.2 
Hematology: Abnormal and clinically significant 
values per visit 
Safety set 
 
 
14.3.4.1.1.3 
Hematology: Shift from baseline 
Safety set 
 
 
14.3.4.1.1.4 
Hematology: CTC Grade per visit 
Safety set 
 
 
14.3.4.1.1.5 
Hematology: CTC Grade shift from baseline 
Safety set 
 
 
 
 
 
 
14.3.4.1.2 
 
Blood Chemistry Data 
 
 
 
14.3.4.1.2.1 
Blood Chemistry: Summary by visit and change 
from baseline 
Safety set 
 
 
14.3.4.1.2.2 
Blood Chemistry: Abnormal and clinically 
significant values per visit 
Safety set 
 
 
14.3.4.1.2.3 
Blood Chemistry: Shift from baseline 
Safety set 
 
 
14.3.4.1.2.4 
Blood Chemistry: CTC Grade per visit 
Safety set 
 
 
14.3.4.1.2.5 
Blood Chemistry: CTC Grade shift from baseline 
Safety set 
 
 
 
 
 
 
14.3.4.1.3 
 
Coagulation Data 
 
 
 
14.3.4.1.3.1 
Coagulation: Summary by visit and change from 
baseline 
Safety set 
 
 
14.3.4.1.3.2 
Coagulation: Abnormal and clinically significant 
values per visit 
Safety set 
 
 
14.3.4.1.3.3 
Coagulation: Shift from baseline 
Safety set 
 
 
14.3.4.1.3.4 
Coagulation: CTC Grade per visit 
Safety set 
 
 
14.3.4.1.3.5 
Coagulation: CTC Grade shift from baseline 
Safety set 
 
 
 
 
 
 
14.3.4.1.4 
 
Urinalysis Data 
 
 


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Header 
Table 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
14.3.4.1.4.1 
Urinalysis dipstick: Summary by visit  
Safety set 
 
 
 
 
 
 
14.3.4.1.5 
 
Thyroid Hormones 
 
 
 
14.3.4.1.5.1 
Thyroid Hormones: Summary by visit and 
change from baseline 
Safety set 
 
 
14.3.4.1.5.2 
Thyroid Hormones: Abnormal and clinically 
significant values per visit 
Safety set 
 
 
14.3.4.1.5.3 
Thyroid Hormones: Shift from baseline 
Safety set 
 
 
 
 
 
 
14.3.4.2 
 
Vital Signs 
 
 
 
14.3.4.2.1 
Vital signs: Summary by visit and change from 
baseline 
Safety set 
 
 
14.3.4.2.2 
Vital signs: Shift from baseline 
Safety set 
 
Figure 
14.3.4.2.3 
Vital signs: Scatter plot per parameter 
Safety set 
 
 
 
 
 
 
14.3.4.3 
 
Electrocardiogram (ECG) Data 
 
 
 
14.3.4.3.1 
12-lead ECG assessment by visit 
Safety set 
 
 
14.3.4.3.2 
Ventricular Heart Rate (bmp): Summary by visit 
and change from baseline 
Safety set 
 
 
 
 
 
 
14.3.4.4 
 
Physical Examination 
 
 
 
14.3.4.4.1 
Physical examination by visit 
Safety set 
 
 
 
 
 
 
14.3.4.5 
 
ECOG data 
 
 
 
14.3.4.5.1 
ECOG performance status by visit 
Safety set 
 
 
14.3.4.5.2 
ECOG performance status: Shift from baseline 
Safety set 
 
 
 
 
 
 
 
 
Note: no table number should go beyond 14.3.4.x (i.e. 14.3.5.x or 14.4.x) 
 
 


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11.1.2 
Listings 
 
Header 
Listing 
Number 
Name 
Analysis Set 
Interim 
Analysis 
16.2 
 
Patient Data Listings 
 
 
16.2.1 
 
Patient Disposition 
 
 
 
16.2.1.1 
Patient disposition 
Screened set 
Yes 
 
16.2.1.2 
Informed consent 
Screened set 
 
 
16.2.1.3 
Patients impacted by COVID-19 related study 
disruption 
ITT set 
 
 
16.2.1.4 
Missing visits due to COVID-19 
ITT set 
 
 
 
 
 
 
16.2.2 
 
Protocol Deviations 
 
 
 
16.2.2.1 
Protocol Deviations 
ITT set 
 
 
16.2.2.2 
Protocol Deviation due to COVID-19 
ITT set 
 
 
 
 
 
 
16.2.3 
 
Patients Excluded from the Efficacy Analysis 
 
 
 
16.2.3.1 
Inclusion/exclusion criteria not met 
Screened set 
 
 
16.2.3.2 
Exclusion from analysis set 
Screened set 
Yes 
 
 
 
 
 
16.2.4 
 
Demographic Data 
 
 
 
16.2.4.1 
Demographics 
ITT set 
Yes 
 
16.2.4.2 
Disease characteristics  
ITT set 
Yes 
 
16.2.4.3 
Medical History 
ITT set 
 
 
16.2.4.4 
Prior systemic cancer therapies 
ITT set 
Yes 
 
16.2.4.5 
Prior cancer radiotherapies 
ITT set 
 
 
16.2.4.6 
Prior cancer surgeries 
ITT set 
 
 
16.2.4.7 
Prior and concomitant medications 
ITT set 
 
 
16.2.4.8 
Further antineoplastic therapies 
ITT set 
 
 
16.2.4.9 
Cancer radiotherapies 
ITT set 
 
 
16.2.4.10 
Procedures and non-drug therapies 
ITT set 
 
 
 
 
 
 
16.2.5 
 
Compliance and/or Drug Concentration Data (if 
available) 
(Note; exposure information will be included in this 
section) 
 
 
 
16.2.5.1 
Trial treatment – W_pro1 
Safety set 
 
 
16.2.5.2 
Trial treatment – Cemiplimab 
Safety set 
 
 
16.2.5.3 
Trial treatment – ADT 
Safety set 
 
 
16.2.5.4 
Drug exposure 
Safety set 
Yes 
 
 
 
 
 
16.2.6 
 
Individual Efficacy Response Data 
 
 
 
 
Primary and Secondary Efficacy Endpoint 
 
 
 
16.2.6.1.1 
Overall PCWG3 and LPC tumor response 
assessment based on Radiological Soft Tissue 
Evaluation per Investigator 
ITT set 
Yes 
 
16.2.6.1.2 
PCWG3 and LPC tumor assessment based on 
Radiological Soft Tissue Evaluation per 
Investigator – target lesions 
ITT set 
Yes 
 
16.2.6.1.3 
PCWG3 and LPC tumor assessment based on 
Radiological Soft Tissue Evaluation per 
Investigator – non-target lesions 
ITT set 
Yes 


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Header 
Listing 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
16.2.6.1.4 
PCWG3 and LPC tumor assessment based on 
Radiological Soft Tissue Evaluation per 
Investigator – new lesions 
ITT set 
Yes 
 
16.2.6.1.5 
PCWG3 Bone lesions based on Radiological Soft 
Tissue Evaluation per Investigator – new lesions 
ITT set 
Yes 
 
16.2.6.1.6 
Clinical progression 
ITT set 
Yes 
 
16.2.6.1.7 
Overall tumor response assessment based on 
PCWG3 
ITT set 
 
 
 
 
 
 
 
16.2.6.2 
Prostate-specific antigen (PSA) 
ITT set 
Yes 
 
 
 
 
 
 
 
Exploratory Efficacy Endpoints 
 
 
 
16.2.6.3.1 
Overall iRECIST (central reading)tumor response 
assessment 
ITT set 
 
 
16.2.6.3.2 
iRECIST (central reading) assessment – target 
lesions 
ITT set 
 
 
16.2.6.3.3 
iRECIST (central reading) assessment – non-
target lesions 
ITT set 
 
 
16.2.6.3.4 
iRECIST (central reading) assessment – new 
lesions 
ITT set 
 
 
 
 
 
 
 
16.2.6.4.1 
Duration of response based on PCWG3 
ITT set 
Yes 
 
16.2.6.4.2 
Duration of response based iRECIST (central 
reading) 
ITT set 
 
 
16.2.6.4.3 
Progression-free survival based on PCWG3  
ITT set 
Yes 
 
16.2.6.4.4 
Progression-free survival based on iRECIST 
(central reading) 
ITT set 
 
 
16.2.6.4.5 
Overall survival time 
ITT set 
 
 
 
 
 
 
 
16.2.6.4.6 
Duration of response based on PCWG3  
Cemi Mono 
on PD set 
 
 
16.2.6.4.7 
Duration of response based on iRECIST (central 
reading) 
Cemi Mono 
on PD set 
 
 
16.2.6.4.8 
Progression-free survival based on PCWG3  
Cemi Mono 
on PD set 
 
 
16.2.6.4.9 
Progression-free survival based on iRECIST 
(central reading) 
Cemi Mono 
on PD set 
 
 
16.2.6.4.10 
Progression-free survival 2 based on PCWG3  
Cemi Mono 
on PD set 
 
 
16.2.6.5.1 
Disease status reported during Survival Follow-up 
ITT set 
 
 
 
 
 
 
 
 
Pharacodynamic and Biomarker Listings 
 
 
 
16.2.6.6.1 
Hormones (Testosterones [nmol/L]) 
Pharmacody
namic set 
 
 
16.2.6.6.2 
Cytokines 
Pharmacody
namic set 
 
 
16.2.6.6.3 
HLA typing (optional) 
Pharmacody
namic set 
 
 
16.2.6.6.4 
Tumor tissue sample (optional) 
ITT set 
 
 
16.2.6.6.5 
TCR profiling (optional) 
Pharmacody
namic set 
 


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Header 
Listing 
Number 
Name 
Analysis Set 
Interim 
Analysis 
 
16.2.6.6.6 
Genetics (optional) 
Pharmacody
namic set 
 
 
 
 
 
 
16.2.7 
 
Adverse Event Listings 
 
 
 
16.2.7.1 
Adverse Events 
Safety set 
Yes 
 
16.2.7.2 
Cemiplimab treatment-emergent adverse events 
Cemi Mono 
on PD set 
 
 
 
 
 
 
16.2.8 
 
Listing of individual laboratory measurements by 
patient 
 
 
 
16.2.8.1.1 
Hematology 
Safety set 
 
 
16.2.8.1.2 
Blood Chemistry 
Safety set 
 
 
16.2.8.1.3 
Coagulation 
Safety set 
 
 
16.2.8.1.4 
Urinalysis dipstick 
Safety set 
 
 
16.2.8.1.5 
Urinalysis microscopic 
Safety set 
 
 
16.2.8.1.6 
Thyroid hormones 
Safety set 
 
 
16.2.8.1.7 
Serology 
Safety set 
 
 
16.2.8.1.8 
Circulating tumor cells 
Safety set 
 
 
 
 
 
 
 
16.2.8.2 
Other Safety Data 
Safety set 
 
 
16.2.8.2.1 
Vital Signs 
Safety set 
 
 
16.2.8.2.2 
12-lead ECG assessment 
Safety set 
 
 
16.2.8.2.3 
Physical examination 
Safety set 
 
 
16.2.8.2.4 
ECOG performance status 
Safety set 
 
 
 
 
 
 
 
Note: no listing number should go beyond 16.2.8.x (i.e. 16.2.9) 
 
 
 


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12 
REFERENCES 
1. Hamberg P, Ratain MJ, Lesaffre E, Verweij J. Dose-escalation models for 
combination phase I trials in oncology. Eur. J. Cancer 2010; 46(16):2870–8. 
2. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, Santis M de, et al. EAU-
ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and 
Local Treatment with Curative Intent. Eur Urol 2017 Apr; 71(4):618–629. 
3. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial Design and 
Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations 
from the Prostate Cancer Clinical Trials Working Group 3. J. Clin. Oncol. 2016 Apr 20; 
34(12):1402–18. DOI: 10.1200/JCO.2015.64.2702. 
4. Seymour L, Bogaerts J, Perrone A, Ford R, Schwartz LH, Mandrekar S, et al. 
iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. 
Lancet Oncol 2017; 18(3):e143-e152. 
5. Simon R. Optimal two-stage designs for Phase II clinical trials. Control Clin. Trials. 
1989 Mar; 10(1):1-10. 
6. U.S. Department of Health and Human Services, Food and Drug Administration, 
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics (available at 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegul
atoryInformation/Guidances/). 
7. U.S. National Comprehensive Cancer Network (NCCN 2020; available at 
https//www.nccn.org/professionals/physician_gls/pdf/prostate.pdf). 
8. Pound CR, Partin AW, Eisenberger MA, et al: Natural History of Progression after PSA 
Elevation Following Radical Prostatectomy. JAMA 281: 1591-1597. 
 
13 
SUPPORTING DOCUMENTATION 
Not applicable 
 
 


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13.1 
Appendix 1: Changes to protocol-planned analyses 
Definition of PP set added in Section 7.1 and supporting analyses of some efficacy 
endpoints using the PP set and ITT set defined. 
Definition of the subsequent cemiplimab monotherapy on progression set added in Section 
7.1. This analysis set has to be used for all exploratory safety and efficacy analyses for the 
Arm 1B patients who are treated with cemiplimab monotherapy following progression after 
W_pro1 monotherapy. 
 
 
 


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13.2 
Appendix 2: List of abbreviations 
 
Abbreviation Definition 
ADT 
Androgen-deprivation therapy 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
AST 
Aspartate Transaminase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BOR 
Best Overall Response 
bpm 
beats per minute 
C 
Cycle 
CI 
Confidence Interval 
CMI 
Cell-mediated immune 
CR 
Complete Response 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-Reactive Protein 
CS 
Clinically Significant 
CT 
Computer tomography 
CTC 
Common Toxicity Criteria 
CTCAE v5.0 
Common Terminology Criteria for Adverse Events, version 5.0 
CTMS 
Clinical Trail Management System 
CTR 
Clinical Trial Report 
D 
Day of cycle 
DI 
Dose intensity 
DL 
Dose level 
DLT 
Dose-limiting toxicity 
DoR 
Duration of response 
DRM 
Data Review Meeting 
eCRF 
Electronic Case Report Form 
ELISpot 
Enzyme-Linked Immuno-Spot 
ECG 
Electrocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
EoT 
End of Treatment 
FDA 
Food and Drug Administration 


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FU 
Follow-up 
GGT 
Gamma-Glutamyl-Transpeptidase 
h 
Hour 
HR 
Hazard Ratio 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IMM 
Immunogenicity 
IMP 
Investigational Medicinal Product 
iRECIST 
Immune-modified Response Evaluation Criteria in Solid Tumors 
ITT 
Intent-To-Treat 
IV 
Intravenous 
LNH 
Low, Normal, High 
LPC 
Localized prostate cancer 
Max 
Maximum 
mCRPC 
Metastatic castration-resistant prostate cancer 
MedDRA™ 
Medical Dictionary for Regulatory Activities 
Mg 
Milligram 
Min 
Minimum 
mITT 
Modified Intent-To-Treat 
mmHg 
millimeter of mercury 
mpMRI 
Multi-parametric MRI 
MRI 
Magnetic resonance imaging 
mRNA (or 
RNA) 
Messenger ribonucleic acid 
N 
Number of Patients 
n 
Number of Observations 
NA 
Not Applicable 
NCI 
National Cancer Institute 
NCS 
Not Clinically Significant 
NE 
Not Evaluable 
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria for Adverse Events 
NIMP 
Non-investigational medicinal product 
OR 
Objective Response 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PCWG3 
Prostate Cancer Working Group 3 
PD 
Progressive Disease 


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PFS 
Progression-Free Survival 
PP 
Per Protocol 
PR 
Partial Response 
PSA 
Prostate-specific antigen 
PSADT 
Prostate specific antigen doubling time 
PT 
Preferred Term 
Q1 
Lower quartile 
Q12W 
Every 12 weeks 
Q3 
Upper quartile 
Q3W 
Every 3 weeks 
QC 
Quality Control 
RBC 
Red Blood Cell 
RDI 
Relative dose intensity 
RECIST 
Response Evaluation Criteria in Solid Tumors 
REDR 
Recommended expansion dose range 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SC 
Subcutaneous(ly) 
SD 
Stable Disease 
SI 
International System of Units 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedures 
SRC 
Safety Review Committee 
TEAE 
Treatment-Emergent Adverse Event 
TFL 
Tables, Figures and Listings 
TMF 
Trial Master File 
TSH 
Thyroid Stimulating Hormones 
ULN 
Upper Limit of Normal 
US FDA 
United States Food and Drug Administration 
V 
Visit 
W_pro1 
W_pro1 cancer vaccine (BioNTech IMP) 
WBC 
White Blood Cell 
WHO DD 
World Health Organization Drug Dictionary 


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13.3 
Appendix 3: Best Overall Response derivation for iRECIST 
Scenarios of assignments of best overall response (iBOR) using iRECIST, based on 
Seymour at all (2017) [4] 
 
 
Time point  
response 1 
Time point  
response 2 
Time point  
response 3 
Time point  
response 4 
Time point  
response 5 
iBOR 
 
 
 
 
 
 
 
Example 1 
iCR 
iCR, iPR, 
iUPD, or NE 
iCR, iPR, 
iUPD, or NE 
iUPD 
iCPD 
iCR 
Example 2 
iUPD 
iPR, iSD, or 
NE 
iCR 
iCR, iUPD, or 
NE 
iCR, iPR, iSD, 
iUPD, iCPD, 
or NE 
iCR 
Example 3 
iUPD 
iPR 
iPR, iSD, 
iUPD, or NE 
iPR, iSD, 
iUPD, NE, or 
iCPD 
iPR, iSD, 
iUPD, NE, or 
iCPD 
iPR 
Example 4 
iUPD 
iSD or NE 
iPR 
iPR, iSD, 
iUPD, or NE 
iPR, iSD, 
iUPD, iCPD, 
or NE 
iPR 
Example 5 
iUPD 
iSD 
iSD, iUPD, or 
NE 
iSD, iUPD, 
iCPD, or NE 
iSD, iUPD, 
iCPD, or NE 
iSD 
Example 6 
iUPD 
iCPD 
Any 
Any 
Any 
iCPD 
Example 7 
iUPD 
iUPD (no 
iCPD) 
iCPD 
Any 
Any 
iCPD 
Example 8 
iUPD 
NE 
NE 
NE 
NE 
iUPD 
Eight examples are presented for patients with target disease at baseline, but many more scenarios exist following the 
same principles. Table assumes a randomised study in which confirmation of complete response or partial response is not 
required. For patients with non-target disease only at baseline, only iCR or non-complete response or non-progression of 
disease can be assigned at each time point (not shown in the table for ease of presentation). “i” indicates immune 
responses assigned using iRECIST. iBOR=best overall response. iCR=complete response. iPR=partial response. NE=not 
evaluable. iUPD=unconfirmed progression. iCPD=confirmed progression. iSD=stable disease. RECIST=Response 
Evaluation Criteria in Solid Tumours. 
See iRECIST guidelines and wording about Best Objective response. See tables 1 and 2 as well from this 
paper: 
“Although the principles of the assignment of the time point response and best overall response closely follow RECIST 
1.1, and reflect assessment of target and non-target lesions as well as the presence of new lesions, the possibility of 
pseudoprogression adds complexity (tables 1–3, panel 2, appendix pp 2–4). The time point response is calculated using 
the response assigned for each category of lesion (as for RECIST 1.1), but takes into account the last time point 
response. 
The algorithm for patients with no previous iUPD is identical to RECIST 1.1. For patients with iUPD at the last time 
point response, the next time point response is dependent on the status of all lesions, including target, non-target, new 
lesion target, and new lesion non-target; on whether any increase in size has occurred (either a further increase in size or 
a sufficient increase to assign a new iUPD if the criteria were not previously met); or the appearance of additional new 
lesions. 
For iRECIST, the best overall response (iBOR) is the best time point response recorded from the start of the study 
treatment until the end of treatment, taking into account any requirement for confirmation. iUPD will not override a 
subsequent best overall response of iSD, iPR, or iCR (tables 1–3, appendix pp 2–4), meaning that iPR or iSD can be 
assigned (time point response or iBOR) even if new lesions have not regressed, or if unequivocal progression (non-
target lesions) remains unchanged, providing that the criteria for iCPD are not met.” 
 
 


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13.4 
Appendix 4: Reporting conventions 
The following treatment labels will be used in the analysis:  
Treatment Group 
Treatment Label 
Treat-
ment 
Code 
Analysis 
Part 1:  
Part 1 mCRPC W_pro1 
1 
Disposition, Demog,  
Efficacy, AE, Safety 
Part 2: Arm 1A 
Part 2 mCRPC W_pro1 + Cemiplimab  
2 
Disposition, Demog, 
Efficacy, AE, Safety 
Part 2: Arm 1B 
Part 2 mCRPC W_pro1  
3 
Disposition, Demog, 
Efficacy, AE, Safety 
Part 2: Arm 2 
Part 2 LPC W_pro1 + Cemiplimab 
4 
Disposition, Demog, 
Efficacy, AE, Safety 
Part 2: Arm 3 
Part 2 LPC W_pro1 
5 
Disposition, Demog, 
Efficacy, AE, Safety 
Combined Treatment 
Groups 
 
 
 
Part 2: Arm 1A and Arm 1B 
Part 2 Total mCRPC 
6 
Disposition, Demog, 
Efficacy, AE, Safety 
Part 2: Arm 2 and Arm 3 
Part 2 Total LPC  
7 
Disposition, Demog, 
Efficacy, AE, Safety 
 
 
 
 
Part 2: Arm 1B and Arm 3 
Part 2 Total Monotherapy 
8 
AE 
Part 2: Arm 1A and Arm 2 
Part 2 Total Combination Therapy 
9 
AE 
 
 
 
 
Part 1 and Part 2: Arm 1A 
and Arm 1B 
Parts 1 and 2 Total mCRPC 
10 
AE 
Part 1 and Part 2: Arm 1B 
and Arm 3 
Parts 1 and 2 Total Monotherapy 
11 
AE 
Part 2: all 4 Arms Combined 
Part 2 Total 
12 
Disposition, Demog 
(optional),  
AE 
All 5 Arms Combined 
Parts 1 and 2 Total 
13 
AE (optional) 
Note: The treatment code will be used in the statistical analysis models.  
 
The column “Analysis” specify which treatment labels / treatment columns to be used for 
which kind of analysis. More details are provided in the separate document “Mock Tables, 
Listings and Figures”. 
 
 
 


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13.5 
Appendix 5: Definition of visceral metastasis 
Definition of visceral metastasis based on location of target or non-target lesions at study entry: 
Location as collected in Database 
Visceral metastasis (Yes or No) 
Prostate 
No 
Lymph node 
No 
Anus 
Yes 
Abdominal Cavity 
Yes 
Adrenal Gland or Adrenal 
Yes 
Biliary Tract 
Yes 
Bladder 
Yes 
Bone 
No 
Brain 
No 
Breast, Bilateral 
No 
Breast, Left 
No 
Breast, Right 
No 
Bronchus 
No 
Chest Wall 
No 
Colon 
Yes 
Esophagus 
Yes 
Gastroesophageal Junction 
Yes 
Head and Neck 
No 
Hypopharynx 
No 
Kidney bilateral 
Yes 
Kidney, Left 
Yes 
Kidney, Right 
Yes 
Large Intestine 
Yes 
Liver 
Yes 
Lung bilateral 
Yes 
Lung, Left 
Yes 
Lung, Right 
Yes 
Oesophagus 
Yes 
Oral Cavity 
No 
Pancreas 
Yes 
Pericardial Effusion 
No 
Peritoneum wall 
Yes 
Pleura wall 
Yes 
Pleural Effusion 
No 
Rectosigmoid Junction 
Yes 
Rectum 
Yes 
Renal 
Yes 
Skin 
No 
Small Intestine 
Yes 
Soft Tissue 
No 
Spinal Cord 
No 
Spleen 
Yes 
Stomach 
Yes 


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Testicle right 
Yes 
Testicle left 
Yes 
Thyroid  
No 
 
 
 


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13.6 
Appendix 5: Schedule of activities 
Schedule of Activities: Part 1 and Part 2 Arms 1A and 1B 
 
Screening 
Treatment 
Follow-up (FU) 
UV 
1 cycle = 21 days 
 
C1[4] 
C2 
C3# 
C4 
C5 
C6 
C7 
C8 
≥C9# 
EoT * 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28d 
≤7d D1 
D8 D15 D1 D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D1 
D30 / 
D90 
M6 M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1
d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
±3d 
 
+7d 
±14
d 
±14
d 
 
Patient 
information/consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history[2] and body 
height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
Physical examination[3] 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X& 
X 
X 
 
 
X[5] 
ECOG PS 
X 
 
X& 
X& 
X& 
X& 
X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
X 
Vital signs[4] 
X 
X 
X&$ X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ 
X 
X 
 
 
X 
Single 12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
X& 
 
 
 
X[5] 
X[5] 
 
 
X[5] 
Concomitant treatment[6, 7] 
X 
X 
X& 
X& 
X& 
X& 
X& X& 
X& 
X 
X& 
X& 
X& 
X& 
X& 
X 
X& 
X 
X 
X 
X 
X[5] 
Tumor response 
assessment[8] 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
X 
X 
X[5] 
 
 
 
X 
Archival FFPE tumor tissue 
sample 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsy sample 
(optional)[10] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional tumor sample[21] 
 
 
(X) 
 
 
 
 


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Screening 
Treatment 
Follow-up (FU) 
UV 
1 cycle = 21 days 
 
C1[4] 
C2 
C3# 
C4 
C5 
C6 
C7 
C8 
≥C9# 
EoT * 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28d 
≤7d D1 
D8 D15 D1 D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D1 
D30 / 
D90 
M6 M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1
d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
±3d 
 
+7d 
±14
d 
±14
d 
 
Inclusion/Exclusion criteria 
X 
X 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization[22] 
 
 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP Administration 
Part 1 (monotherapy dose titration)  
W_pro1 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Part 2 Arm 1A (with cemiplimab) 
W_pro1 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Cemiplimab (IMP) 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Part 2 Arm 1B (monotherapy) 
IMP 1 admin. Arm: W_pro1 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
Safety laboratory tests [11] 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
X 
 
X& 
X& 
X& 
X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
X [5]  
Coagulation 
 
X 
 
 
 
X& 
 
 
 
 
X& 
 
X& 
 
X& 
 
X& 
X 
X 
 
 
X [5] 
Blood chemistry 
 
X 
 
X& 
X& 
X& 
X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
(X) [5] 
Thyroid hormones [18, 20] 
 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X20 
 
X 
 
 
(X)[5] 
Urinalysis 
 
X 
 
X& 
X& 
X& 
X& X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X& 
X 
X 
 
 
(X) [5] 
 
AE/TEAE [12, 13] 
X 
X 
X&$ X&$ X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ 
X 
X 
 
 
X 
Survival/disease status [14] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Blood Biomarkers 
Cytokines 
 
 
X[15] X[15] X[15] X[15] X[15] X[15] X[15] 
 
X[17] X[17] X[17] X[17] X[17] 
 
X[17] 
X 
X 
 
 
(X) 


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Screening 
Treatment 
Follow-up (FU) 
UV 
1 cycle = 21 days 
 
C1[4] 
C2 
C3# 
C4 
C5 
C6 
C7 
C8 
≥C9# 
EoT * 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28d 
≤7d D1 
D8 D15 D1 D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D1 
D30 / 
D90 
M6 M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1
d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
±3d 
 
+7d 
±14
d 
±14
d 
 
PSA 
 
X 
X[16] X[16] X[16] X[16] X 
[16] X[16] X[16] 
 
X[16] X[16] X[16] X[16] X[16] 
 
X[16] 
X 
X 
 
 
(X) 
Testosterone 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
ELISpot and further 
immune monitoring 
 
X[18] 
 
 
  
 
 
 
X 
 
 
 
 
 
X 
 
X[19] 
X[19] 
 
 
(X) 
HLA typing 
 
X[18] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCR profiling 
 
X[18] 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X[19] 
X[19] 
 
 
(X) 
Circulating tumor cells [9] 
(X) 
(X) 
 
 
 
 
Abbreviations and Footnotes: 
X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done before and after IMP administration; (X) = optional; AE = adverse event; C = cycle (One 
cycle is defined as 21 days); D = day of cycle; d = day(s); DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group performance status; h = 
hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; FFPE = formalin-fixed, paraffin-embedded; FU = follow-up; HLA = human leukocyte antigen; IMP = 
investigational medicinal product; PSA = prostate-specific antigen; SRC = Safety Review Committee; TCR = T cell receptor; TEAE = treatment-emergent AE; UV = unscheduled visit. 
# 
Starting with C3D1, treatment will be administered every 3 weeks until a discontinuation-of-treatment criterion is met. Planned visit schedule until C8 is shown in table. From Cycle 8 on, 
coagulation, blood chemistry, hematology, and urinalysis will be measured every second cycle (i.e., C8, C10, C12, etc.) unless clinically indicated. 
* 
EoT assessments will be performed up to 21 days after administration of the last dose of IMP for patients who discontinued trial treatment, except if patient was lost to follow-up or died or the 
EoT visit may be combined with the Safety FU-D30 visit. For patients of Arm 1B who will optionally start cemiplimab monotherapy as outlined in the Schedule of Activities shown in Section 
1.5 in the protocol, the EoT visit may be combined with visit CemC1 if both visits are to happen with less than 7 days difference. 
** 
All patients (Part 1 and 2) will be actively followed up for safety (FU-D30) after last intake of W_pro1. Patients in Part 2 Arm 1A will be followed up for safety (FU-D90) after last intake of 
cemiplimab or (FU-D30) after last intake of W_pro1, whichever is later. All patients will be followed up for efficacy (FU-M6 after the last intake of IMP, FU-M12 after the last intake of IMP). 
Within 28 days after confirmation of disease progression, patients of Arm 1B can optionally start cemiplimab monotherapy and will follow the Schedule of Activities shown in Section 1.5 in 
the protocol after performing the EoT for W_pro1 treatment.  
[1] 
The patient ICF for trial participation must be signed before any trial-related research procedures or interventions are performed, see Section 10.1.3 in the protocol. Patients who agree to 
additional optional tumor biopsy sample(s) in case these are taken at the time of disease progression must give written consent for this. Refusal to give consent for the optional tumor biopsy 
sample(s) does not exclude a patient from participation in the trial. 
[2] 
Documentation of prostate cancer history and treatments, previous/ongoing concomitant diseases and tetanus vaccination status (see Section 8.3.2 in the protocol).  


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[3] 
A comprehensive physical examination will be performed at screening and abbreviated physical examinations (overall health judgment and change of symptoms) from C1D1 onwards prior to 
IMP administration, see Section 8.2.1 in the protocol. 
[4] 
Vital signs (blood pressure, pulse rate, body temperature) should be assessed pre-treatment and 1 h (±15 min), 4 h (±1 h) and 6 h (±1 h) post-treatment and as clinically indicated during C1. 
Patients must be observed for at least 4 to 6 h after administration of W_pro1 and vital signs collected pre-treatment, 4 to 6 h (±1 h) post-treatment and as clinically indicated. 
[5] 
Only if clinically indicated. 
[6] 
All prior prostate cancer-related drug treatment will be recorded; other prior medication only for the period of 28 days before the planned IMP administration. 
[7] 
The period for documentation of concomitant treatment extends from C1D1 until Safety FU-D30 visit. Details of systemic anti-cancer treatments or non-drug anti-cancer therapies (e.g., 
radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of the FU period (i.e., up to Efficacy FU-M12). 
[8] 
Bone scans and CT/MRI of the chest, abdomen, and pelvis will be done at screening, every 8 weeks for the first 24 weeks and every 3 months thereafter (window for tumor assessment is ±7 
days of respective visit day). PCWG3 and iRECIST guidelines for imaging will apply. See Section 8.1.1.1 in the protocol. 
[9] 
Only if routinely performed locally.  
[10] 
Patients in Part 1 and Part 2 Arm 1A and Arm 1B will be asked if they are willing to provide optional tumor biopsy sample(s) in case these are taken at the time of disease progression.  
[11] 
For details on safety laboratory tests, see Section 10.2 in the protocol. If the time interval between screening laboratory tests and C1D1 (baseline) is more than 7 days, tests must be repeated at 
C1D1. Screening serum creatinine will be used to calculate patient’s glomerular filtration rate required for inclusion criterion. If warranted by dipstick results, urine sediment will be 
microscopically examined. Serology can be done at earlier screening time point. 
[12] 
At treatment visits, patients will also be monitored for TEAEs for at least 4 to 6 h post-treatment. 
[13] 
For details on DLT assessment period and DLT criteria, see Sections 6.6.1.2 and 6.6.1.1 in the protocol. 
[14] 
For details on patient’s survival status and disease status, see Sections 10.9 and 8.1 in the protocol. 
[15] 
Blood collection before and 4 h (±30 min) after administration of W_pro1. 
[16] 
Blood collection before administration of W_pro1. 
[17] 
Blood collection 4 h (±30 min) after administration of W_pro1. 
[18] 
Variable time point; either during screening ≤7 d or at C1D1 before administration of W_pro1. 
[19] 
A sample should be taken at EoT or at Safety FU and only if one has not previously been taken at C8D15. 
[20] 
At screening for all patients, thereafter only for Arm 1A: thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) will be performed at the times 
listed and every second cycle after C8 and when clinically indicated at the investigator’s discretion. 
[21] 
On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for additional potential 
biomarker research. 
[22] 
Randomization can be performed up to 1 day before C1D1. 
 


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Schedule of Activities: Part 2 Arms 2 and 3 
 
Screenin
g 
 
Treatment 
Follow-up (FU) 
UV Surgery 
1 cycle = 21 days 
 
 
C1 
C2 
C3 
C4 
C5 
C6 
C7 
C8 
EoT* 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28
d 
≤7d 
D1 
D8 D15 D1 
D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D30/ 
D90 
M6  
M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
 
+7d 
±14d ±14d 
Patient information/ 
consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history[2] and 
body height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body weight 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
 
 
 
X 
X 
 
 
 
 
Physical examination[3] 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
 
 
X[5] 
 
ECOG PS 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X 
 
Vital signs[4] 
X 
X 
X&$ 
X&$ 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X 
X 
 
 
X 
 
Single 12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
X& 
 
 
X& 
 
 
X[5] 
X[5] 
 
 
X[5] 
 
Concomitant    
treatment[6, 7] 
X 
 
X 
X& 
X& 
X& 
X& 
X& 
X& 
X& 
X 
X& 
X& 
X& 
X& 
X& 
X 
X 
X 
X 
X 
X[5] 
 
Tumor response 
assessment[8, 13] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
(X) 
 
 
 
X 
(X) 
Tumor tissue 
(mandatory)[9] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Optional tumor 
sample[22] 
 
 
(X) 
 
 
 
 
 
Inclusion/Exclusion 
criteria 
X 
X 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization[23] 
 
 
X& 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP/NIMP administration: 


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Screenin
g 
 
Treatment 
Follow-up (FU) 
UV Surgery 
1 cycle = 21 days 
 
 
C1 
C2 
C3 
C4 
C5 
C6 
C7 
C8 
EoT* 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28
d 
≤7d 
D1 
D8 D15 D1 
D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D30/ 
D90 
M6  
M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
 
+7d 
±14d ±14d 
Part 2 Arm 2 (with cemiplimab)  
W_pro1 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Cemiplimab (IMP) 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
ADT (NIMP) [11] 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 


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Screenin
g 
 
Treatment 
Follow-up (FU) 
UV Surgery 
1 cycle = 21 days 
 
 
C1 
C2 
C3 
C4 
C5 
C6 
C7 
C8 
EoT* 
Safety 
FU ** 
Efficacy 
FU ** 
Visit 
≤28
d 
≤7d 
D1 
D8 D15 D1 
D8 D15 D1 D15 D1 
D1 
D1 
D1 
D1 D15 
D30/ 
D90 
M6  
M12 
Visit window 
 
 
 
±1d ±1d ±1d ±1d ±1d ±1d ±3d ±1d ±1d ±1d ±1d ±1d ±3d 
 
+7d 
±14d ±14d 
Part 2 Arm 3 (monotherapy) 
W_pro1 (IMP) 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
ADT (NIMP) [11] 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests [12] 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X[5] 
 
Coagulation 
 
X 
 
 
 
X& 
 
 
 
 
X& 
 
X& 
 
X& 
 
X 
X 
 
 
X[5] 
 
Blood chemistry 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X[5] 
 
Thyroid hormones [19, 
21] 
 
X 
 
 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
(X)[5] 
 
Urinalysis 
 
X 
 
X& 
X& 
X& 
X& 
X& 
X& 
 
X& 
X& 
X& 
X& 
X& 
 
X 
X 
 
 
X 
 
 
AE/TEAE[14] 
X 
X 
 
X&$ 
X&$ 
X&$ X&$ X&$ X&$ X&$ 
X 
X&$ X&$ X&$ X&$ X&$ 
X 
X 
X 
 
 
X 
 
Survival/disease 
status[15] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Blood Biomarkers 
Cytokines  
 
 
X[16] 
X[16] X[16] X[16] X[16] 
 
X[16] 
 
X[18] X[18] X[18] X[18] X[18] 
 
X 
X 
 
 
(X) 
 
PSA  
 
X 
X[17] 
X[17] X[17] X[17] X[17] X[17] X[17] 
 
X[17] X[17] X[17] X[17] X[17] 
 
X 
X 
X 
X 
(X) 
X [20] 
ELISpot and further 
immune monitoring 
 
X[19] 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
X[10] 
X[10] 
 
 
(X) 
 
HLA typing  
 
X[19] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCR profiling  
 
X[19] 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X[10] 
X[10] 
 
 
(X) 
 
 


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Version: Final v 2.0 
Date: 27 APR 2023 
 
 
Abbreviations and Footnotes 
X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done before and after IMP administration; (X) = optional; ADT = androgen-deprivation therapy 
(e.g., goserelin acetate); AE = adverse event; C = cycle (One cycle is defined as 21 days); CT = computed tomography; D = day of cycle; d = day(s); ECG = electrocardiogram; ECOG PS = Eastern 
Cooperative Oncology Group performance status; h = hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; FFPE = formalin-fixed, paraffin-embedded; FU = follow-up; 
HLA = human leukocyte antigen; IMP = investigational medicinal product; mpMRI = multi-parametric magnetic resonance imaging; MRI = magnetic resonance imaging; NIMP = non-
investigational medicinal product; PSA = prostate-specific antigen; REDR = recommended expansion dose range; TCR = T cell receptor; TEAE = treatment-emergent adverse event; UV = 
unscheduled visit; h = hour(s). 
* 
EoT assessments will be performed up to 21 days after administration of the last dose of IMP for patients who discontinued trial treatment, except if patient was lost to follow-up or died or the 
EoT visit may be combined with the Safety FU-D30 visit.  
** 
All patients (Part 1 and 2) will be actively followed up for safety (FU-D30) after last intake of W_pro1. Patients in Part 2 Arm 2 will be followed up for safety (FU-D90) after last intake of 
cemiplimab or (FU-D30) after last intake of W_pro1, whichever is later. Efficacy FU-M6 and M12 are performed for Part 2 Arms 2 and 3 after last IMP administration 
[1] 
The patient ICF for trial participation must be signed before any trial-related research procedures or interventions are performed, see Section 10.1.3 in the protocol. Patients who agree to 
additional optional sampling must give written consent for this. Refusal to give consent for the optional sample(s) does not exclude a patient from participation in the trial, see Section 10.1.3 in 
the protocol. 
[2] 
Documentation of prostate cancer history and treatments, previous/ongoing concomitant diseases and tetanus vaccination status (see Section 8.3.2 in the protocol).  
[3] 
A comprehensive physical examination will be performed at screening and abbreviated physical examinations overall health judgment and change of symptoms) from C1D1 onwards prior to 
IMP administration, see Section 8.2.1 in the protocol. 
[4] 
 For all patients, vital signs (blood pressure, pulse rate, body temperature) should be assessed pre-treatment and 1 h (±15 min), 4 h (±1 h) and 6 h (±1 h) post-treatment and as clinically 
indicated during C1. Patients must be observed for at least 4 to 6 h after administration of W_pro1 and vital signs collected pre-treatment, 4 to 6 h (±1 h) post-treatment and as clinically 
indicated. 
[5] 
Only if clinically indicated. 
[6] 
All prior prostate cancer-related drug treatment will be recorded; other prior medication only for the period of 28 days before the planned IMP administration.  
[7] 
The period for documentation of concomitant treatment extends from C1D1 until Safety FU-D30 visit (Part 2 Arm 3) or FU-D90 (Part 2 Arm 2). Details of systemic anti-cancer treatments or 
non-drug anti-cancer therapies (e.g., radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of the FU period (i.e., up to Efficacy FU-
M12).  
[8] 
Tumor measurement using mpMRI or MRI (window for tumor assessment is ±7 days of respective visit day). The same imaging modality should be used at screening and at all subsequent 
assessments. For details on tumor imaging and time points, see Section 8.1.1 in the protocol.  
[9] 
An FFPE tumor sample from the diagnostic biopsy must be provided during screening. A fresh tissue sample must be provided from surgery; only if this is not feasible an FFPE tumor sample 
will be obtained.  
[10] 
A sample should be taken at EoT or at Safety FU and only if one has not previously been taken at C8D15. 
[11] 
The ADT administration should take place between 7 days before Day 1 and 12 weeks after the first administration. 
[12] 
For details on safety laboratory tests, see Section 10.2 in the protocol. If time interval between screening laboratory tests and C1D1 (baseline) is more than 7 days, tests must be repeated at 
C1D1. Screening serum creatinine will be used to calculate patient’s glomerular filtration rate required for inclusion. If warranted by dipstick results, urine sediment will be microscopically 
examined. Serology can be done at earlier screening time point. 
[13] 
For details on response assessment, please refer to Section 8.1.1.2 in the protocol. 
[14] 
At treatment visits, patients will also be monitored for TEAEs 4 to 6 h post-treatment. 


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Confidential 
Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
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[15] 
For details on patient’s survival status and disease status, see Section 10.9 and 8.1 in the protocol. 
[16] 
Blood collection before and 4 h after administration of W_pro1. 
[17] 
Blood collection before administration of W_pro1. 
[18] 
Blood collection 4 h (±30 min) after administration of W_pro1. 
[19] 
Variable time point; either during screening ≤7 d or at C1D1 before administration of W_pro1. 
[20] 
At 6 weeks (± 1 week) after the surgery (radical prostatectomy). 
[21] 
Only for Arm 2 (and at screening for all patients if the patient is not yet randomized), thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) 
will be performed at the times listed and as clinically indicated at the investigator’s discretion. 
[22]  On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for additional 
potential biomarker research. 
[23] 
Randomization can be performed up to 1 day before C1D1. 
 
 
 
 


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Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
Page 103 of 107 
Version: Final v 2.0 
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Schedule of Activities: Part 2 Arms 1B – Optional Cemiplimab Treatment Following Progression after 
W_pro1 monotherapy 
 
Treatment# 
Follow-up (FU) 
UV 
1 cycle = 21 days 
CemC1 
≥CemC2 
EoT * 
Safety FU ** 
Efficacy FU ** 
Visit 
 
 
 
D90 
M6 
M12 
Visit window 
≤28 d after 
progression in Arm 1b 
±3d 
  
+7d 
±14d 
±14d 
 
Patient information/consent 
for cemiplimab 
monotherapy[1] 
X@ 
 
 
 
 
 
 
Physical examination[2] 
X& 
X& 
X 
X 
 
 
X[3] 
ECOG PS 
X& 
X& 
X 
X 
 
 
X 
Vital signs 
X&$ 
X&$ 
X 
X 
 
 
X 
Single 12-lead ECG 
X& 
X&[14] 
X[3] 
X[3] 
 
 
X[3] 
Concomitant treatment[5] 
X& 
X& 
X 
X 
X 
X 
X[3] 
Tumor response 
assessment[6] 
X 
X[3] 
 
 
 
 
Optional tumor sample[7] 
(X) 
 
 
 
 
IMP Administration 
Cemiplimab (IMP) 
X 
X 
 
 
 
 
 
Safety laboratory tests [8] 
Hematology 
X& 
X& 
X 
X 
 
 
X[3] 
Coagulation[4] 
X& 
X 
X 
 
 
X[3] 
Blood chemistry 
X& 
X& 
X 
X 
 
 
(X)[3] 
Thyroid hormones[4] [9]  
X 
 
X 
 
 
(X)[3] 
Urinalysis 
X& 
X& 
X 
X 
 
 
(X)[3] 
 
AE/TEAE [10] 
X&$ 
X&$ 
X 
X 
 
 
X 
Survival/disease status [11] 
 
 
 
 
X 
X 
 


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Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
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Date: 27 APR 2023 
 
 
 
Treatment# 
Follow-up (FU) 
UV 
1 cycle = 21 days 
CemC1 
≥CemC2 
EoT * 
Safety FU ** 
Efficacy FU ** 
Visit 
 
 
 
D90 
M6 
M12 
Visit window 
≤28 d after 
progression in Arm 1b 
±3d 
  
+7d 
±14d 
±14d 
 
Blood Biomarkers 
PSA 
X& 
X& 
X 
X 
 
 
(X) 
Testosterone 
 
 
 
 
 
 
(X) 
ELISpot and further immune 
monitoring 
 
X[12] 
 
 
 
 
TCR profiling 
 
X[12] 
 
 
 
 
Circulating tumor cells [13] 
(X) 
 
 
 
 
 
Abbreviations and Footnotes: 
X@ to be done before any CemC1-specific procedure or intervention; X& = to be done before IMP administration; X$ = to be done after IMP administration; X&$ = to be done before and after IMP 
administration; (X) = optional; AE = adverse event; CemC = cycle (One cycle is defined as 21 days); d = day(s); ECG = electrocardiogram; ECOG PS = Eastern Cooperative Oncology Group 
performance status; h = hour(s); ELISpot = enzyme linked immunospot (assay); EoT = End of Treatment; FFPE = formalin-fixed, paraffin-embedded; FU = follow-up; IMP = investigational 
medicinal product; mCRPC = metastatic castration-resistant prostate cancer; PSA = prostate-specific antigen; SRC = Safety Review Committee; TCR = T cell receptor; TEAE = treatment-emergent 
adverse event; UV = unscheduled visit. 
# 
Treatment will be administered every 3 weeks until a discontinuation-of-treatment criterion is met. 
* 
EoT assessments will be performed up to 21 days after administration of the last dose of cemiplimab for patients who discontinued trial treatment, except if patient was lost to follow-up or 
died.  
** 
All patients will be actively followed up for safety (FU-D90) after last intake of cemiplimab. All patients will be followed up for efficacy (FU-M6 after the last intake of IMP, FU-M12 after the 
last intake of IMP). 
[1] 
The patient ICF for cemiplimab monotherapy must be signed before any trial-related research procedures or interventions are performed on CemC1, see Section 10.1.3 in the protocol. Patients 
who agree to additional optional sampling must give written consent for this. Refusal to give consent for the optional sample(s) does not exclude a patient from participation in this part of the 
trial, see Section 10.1.3 in the protocol. 
[2] 
A comprehensive physical examination will be performed at CemC1 and abbreviated physical examinations (overall health judgment and change of symptoms) from CemC2 onwards prior to 
IMP administration, see Section 8.2.1 in the protocol. 
[3] 
Only if clinically indicated. 
[4] 
Assessments will be performed at CemC1 and then every second cycle (every 6 weeks) 
[5] 
The period for documentation of concomitant treatment extends from CemC1 until Safety FU-D90 visit. Details of systemic anti-cancer treatments or non-drug anti-cancer therapies (e.g., 
radiotherapy, surgical therapeutic procedures) started after discontinuation of IMP will be recorded up to the end of the FU period (i.e., up to Efficacy FU-M12).  
[6] 
Bone scans and CT/MRI of the chest, abdomen, and pelvis will be done every 3 months (window for tumor assessment is ±7 days of respective visit day). PCWG3 and iRECIST guidelines for 
imaging will apply. See Section 8.1.1.1 in the protocol. 


BioNTech SE 
Confidential 
Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
Page 105 of 107 
Version: Final v 2.0 
Date: 27 APR 2023 
 
 
[7] 
On-treatment tumor samples from biopsies or tumor resections done as part of the clinical management of the patient (e.g., palliative surgery) will optionally be provided for additional potential 
biomarker research. 
[8] 
For details on safety laboratory tests, see Section 10.2 in the protocol. If warranted by dipstick results, urine sediment will be microscopically examined. 
[9] 
Thyroid hormones (thyroid stimulating hormone [TSH], free thyroxine [fT4] and triiodothyronine [T3]) will be performed every 6 weeks, at Safety FU D90, or as clinically indicated at the 
investigator’s discretion. 
[10] 
At treatment visits, patients will also be monitored for TEAEs at site, according to local prescribing guidelines for cemiplimab. 
[11] 
For details on patient’s survival status and disease status, see Sections 8.1 and 10.9 in the protocol. 
[12] 
Sampling at CemC3 or at EoT, whichever occurs first. 
[13] 
Only if routinely performed locally. 
[14] 
Assessments will be performed at CemC1, CemC4, CemC7 and when considered as clinically indicated by the investigator. 
 
 
 
 
 
 


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Statistical Analysis Plan (SAP) 
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Page 106 of 107 
Version: Final v 2.0 
Date: 27 APR 2023 
 
 
13.7 
Appendix 6: Laboratory parameters to be categorized by Toxicity Grades (NCI CTCAE v5.0)  
 
Parameters (by group) 
Hematology: 
• 
Hemoglobin decrease / Hemoglobin increase 
• 
WBC decrease 
• 
Neutrophils decrease 
• 
Lymphocytes decrease 
• 
Eosinophils increase 
• 
Platelet count decrease 
 
Coagulation: 
• 
Activated partial thromboplasting time (APTT) increase 
• 
International normalized ratio (INR) increase 
• 
Fibrinogen decrease 
 
Blood Chemistry: 
• 
Amylase increase 
• 
Alkaline phosphatase (ALP) increase 
• 
Alanine aminotransferase (ALT) increase 


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Statistical Analysis Plan (SAP) 
RN5609C00/PRO-MERIT 
Page 107 of 107 
Version: Final v 2.0 
Date: 27 APR 2023 
 
 
• 
Asparate aminotransferase (AST) increase 
• 
Gamma glutamyl transpeptidase (GGT) increase 
• 
Total bilirubin increase 
• 
Glucose decrease / Glucose increase 
• 
Sodium decrease / Sodium increase 
• 
Potassium decrease / Potassium increase 
• 
Calcium decrease / Calicum increase 
 


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