A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ESCALATING DOSES OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN (VBIR) FOR PROSTATE CANCER (PF-06753512)
Phase: PHASE1
Conditions: Prostatic Neoplasms
Sponsor: Pfizer

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 1
A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND 
PHARMACODYNAMICS OF ESCALATING DOSES OF A VACCINE-BASED 
IMMUNOTHERAPY REGIMEN (VBIR) FOR PROSTATE CANCER (PF-06753512)
Compound:
PF-06753512
Compound Name:
Not applicable
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
Not applicable
Protocol Number:
B7791001
Phase:
Phase 1
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in writing, 
by accepting or reviewing this document, you agree to hold this information in confidence and not copy or 
disclose it to others (except where required by applicable law) or use it for unauthorized purposes.  In the event 
of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 2
DOCUMENT HISTORY
Document
Version Date
Summary of Changes and Rationale
Amendment 8
29 May 2020
Overall reasons for Amendment 8: 

Change in Study Design (Section 3): Cohort 
3B will be reduced from 40 to 18 participants 
total.
Rationale: As regards the two cohorts with 
mCRPC, there is now sufficient sample size 
(n=33) to make an internal decision about further 
development of Pr Ca VBIR, based upon 
preliminary efficacy and safety. As such, there is 
no need to enroll additional participants.  

Change in Study Design (Section 3): Cohort 
5B will be reduced from 40 to 15 participants
total.
Rationale: Fifteen patients is considered a 
sufficient sample size to provide preliminary 
efficacy, safety, PK and biomarker data for the 
regimen. 

Change in Study Design (Section 3): 
Deletion of Cohort 10B. 
Rationale: Studies of progression on 
novel-hormone therapy with abiraterone, with a 
switch to enzalutamide + Pr Ca VBIR, are no 
longer useful in defining Proof of Concept for 
this study.

Deletion of inclusion criteria for Cohort 10B
patients – Section 4.1.3.
Rationale: The combination of PrCa VBIR and 
enzalutamide will not be evalauted.

Section 4.2 Exclusion criterion for 
COVID-19/SARS-CoV2 infection added. 
Rationale: Guidance regarding 
COVID-19/SARS-CoV2 infection was required.  

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 3
Document
Version Date
Summary of Changes and Rationale

Revisions to Objectives and Endpoints 
(Section 2).
Rationale: For consistency with changes in Study 
Design.

DTH and skin punch biopsy were deleted. 
Rationale: No additional patients will be enrolled. 

Clinical and safety information was updated, 
including risk of myocarditis.
Rationale: New safety information from the 
VBIR PrCa PF-06753512 January 2020 IB 
(adenovirus, plasmid DNA and anti-CTLA4 
tremelimumab) and from safety reports has been
incorporated.

Cardiac troponin I testing was added at 
screening and post-baseline time points
(SOA and Section 7). 
Rationale: Based on emerging safety information 
cardiac monitoring was added to mitigate the risk 
of myocarditis.

Enzalutamide rationale, PK, safety, dosing 
and product administration information was 
deleted (Sections 1.3.3, 1.5, 1.6, 3.1.2 and 5).
Rationale: The combination of PrCa VBIR and 
enzalutamide will not be evaluated.

Section 5.4.3 Added recommendations for 
dose interruptions/delays due to Non-related 
Adverse Events.
Rationale: Dose interruptions due to reasons other 
than treatment-related toxicity include guidance 
for COVID-19/SARS-CoV2 infection.
Amendment 7
22 November 
2019

Overall reasons for Amendment 7: Increased 
Cohort 3B and 5B sample size. Addition of new 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 4
Document
Version Date
Summary of Changes and Rationale
Cohort 10B. 
Rationale: ESOE assessment and evaluation of 
regimen in combination with enzalutamide.

New Schedule of Activities (SOA): Updated for 
Part B Expansion Cohorts.
Rationale: New SOA required for Part B.

Section 1.2 Background and Rationale: Updated 
prostate cancer statistics; rationale for Part B 
participant populations. 
Rationale: Provide background to support 
changes in Part B Dose Expansion Cohorts.

Section 1.3 PF-06753512: Updated components
of the PrCa VBIR regimen.
Rationale: Sunitinib will not be tested with the 
PrCa VBIR regimen; added rationale for 
combination with PF-06801591 and 
enzalutamide. 

Section 1.5 Pharmacokinetics of tremelimubab, 
PF-06801591 and Enzalutamide: Updated PK 
data, added enzalutamide PK data; deleted 
sunitinib PK data.
Rationale: New PK data available; enzalutamide 
combination added; sunitinib will not be tested 
with the PrCa regimen.

Section 1.6 Starting Dose Rationale: Modified 
background information and starting dose
rationale for PrCa VBIR components.
Rationale: Updated PF-06801591 information; 
added enzalutamide and deleted sunitinib 
background information and starting dose 
rationale.

Section 2.1 and 2.2 Part A Objectives and 
Endpoints: Deleted objectives and endpoints of 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 5
Document
Version Date
Summary of Changes and Rationale
combination with sunitinib.
Rationale: Sunitinib will not be tested with the 
PrCa VBIR regimen. 

2.3 Part B Objectives and Endpoints: Added 
Part B (Expansion) objectives and endpoints.
Rationale: Part B Objectives and endpoints are 
listed. Anti-tumor activity objectives and 
endpoints are defined for the different Part B 
Cohort populations. 

Study Design Section 3.1.1 Part A: Findings from 
Part A added.
Rationale: To support Part B Cohorts, regimens 
and doses.

Change in Study Design Section 3.1.2
Part B: Modified Expansion Cohorts: a) Sunitinib 
cohorts (5A and 4B) were deleted; b) Expansion 
Cohorts 3B and 5B were expanded from 15 to 
40 participants total; c) Expansion Cohort 10B 
(PrCa VBIR + enzalutamide) was added.   
Rationale for deletion of Sunitinib Cohorts: In 
previous versions of Study B7791001, sunitinib 
was proposed to be combined with PrCa VBIR 
because of preclinical evidence showing the 
positive effect of combining sunitinib with VBIR. 
However, recent work in the field of 
immunotherapy has focused intensive efforts on 
checkpoint inhibitors as stimulants of 
T-cell-modulated anti-cancer therapy. Given 
more recent evidence of successful use of 
checkpoint inhibitors in metastatic prostate 
cancer, the use of sunitinib was replaced with that 
of tremelimumab (anti-CTLA-4) and RN-888 
(anti-PD-1) antibodies.
Rationale for Expansion of Cohorts 3B and 5B: to 
further evaluate the Expansion Doses for each, 
the metastatic participants and the biochemical 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 6
Document
Version Date
Summary of Changes and Rationale
relapse prostate cancer populations.
Rationale for adding Expansion Cohort 10B: 
Enzalutamide resistance may be associated with 
increased expression of anti-PD-1. Cohort 10B 
will evaluate the anti-tumor response induced by 
PrCa VIBR + enzalutamide in participants with 
mCRPC whose disease progressed on 
abiraterone.  

Change in Study Design Section 3.1.2.1 Part B: 
Cohort 10B lead-in was added including the 
mTPI decision chart and dose de-escalation 
schema. 
Rationale: The dose-de-escalation lead-in will be 
implemented to determine the most appropriate 
regimen for Cohort 10B.  

Change in Study Design Section 3.1.2.1 Drug 
regimens and doses for Part B Expansion Cohorts 
defined.  
Rationale: Safety data from Cohorts 3B and 
7A support Part B Expansion regimens and doses. 

Change in Section 4 Participant selection: Added 
Inclusion and Exclusion Criteria for Part B 
Cohorts.  
Rationale: Eligibility criteria defined for new 
populations in Part B Expansion Cohorts. 

Delete population specific exclusion criteria 26 to 
36.
Rationale: to facilitate review of eligibility in 
different participant populations.

Changes in Section 5 Study Treatments: supply 
for Part B defined, dose modifications for toxicity 
and prohibited medications amended.  
Rationale: Sections were updated based on 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 7
Document
Version Date
Summary of Changes and Rationale
regimens and doses for each of Part B Cohorts. 
 
 
 
 
 
 
Amendment 6
11 May 2018
The reasons for Amendment 6 include:
•
Change: Clarification was provided for the 
Inclusion/Exclusion Criteria (Inclusion #10(a), 
#13, #14; Exclusion #2 and #38 (removed), 
[previously numbered #6, #10, #20, #23, and 
#29].
Rationale: (Pre-Secondary Hormone) Inclusion 
#10(a): ‘PSA progression defined as a minimum 
of 2 consecutive rising levels, with an interval of 
≥1 week between each determination.’  The 
reduction from 3 to 2 consecutive rising levels 
does not effect the safety for the patient 
population.  
Rationale: (Biochemical Relapse) Inclusion #13: 
Refined the definition for relapsing prostate 
cancer post-definitive local therapy.  ‘Hormone 
sensitive (androgen dependent) relapsing prostate 
cancer post definitive local therapy.  Relapse is 
defined as a subsequent detectable PSA 
(0.2 ng/ml) that increases on 2 or more 
determination after radical prostectomy. At least 
2 PSA values with PSA1 < PSA2, each value 
separated by at least 2 weeks.’
Rationale: (Biochemical Relapse) Inclusion #14: 
Refined the definition for ‘High risk of 
development of metastatic disease defined as 
PSA doubling time less than or equal to 
10 months (calculated considering at least 
3 months before treatment administration).’  PSA 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 8
Document
Version Date
Summary of Changes and Rationale
doubling time change from 12 to 10 months does 
not effect the safety of the patient population.
Rationale: (Post-Secondary Hormone) Inclusion 
#18: (a) ‘PSA progression defined as a minimum 
of 2 consecutive rising levels, with an interval of 
1 week between each determination.’ The 
change from 3 to 2 consecutive rising PSA levels 
does not effect the safety of the population.
Rationale: Exclusion #2: Removed 
– ‘Cancer-raleted pain requiring scheduled 
opioid narcotics for control (as needed, 2 times 
per week is allowed).’  The removal of Exclusion 
Criteria #2 does not effect the safety of the 
patient population.
Rationale: Exclusion #5 (previously #6) 
– Provided clarification on palliative radiation 
therapy prior to- and during study participation. 
‘Radiation therapy within 4 weeks of starting 
study treatment, except: palliative radiotherapy 
to a limited field is allowed after consultation 
with the sponsor’s medical monitor at any time 
during study participation, including during 
screening.’
Rationale: Exclusion #9 (previously #10)
– Provided clarification on Concurrent 
chemotherapy in the hormone sensitive setting is 
acceptable, provided the time from last treatment 
is >4 weeks from first dose. Removed “Prior 
or”and lessened the last treatment from 
6 months to >4 weeks.  The changes do not 
effect the safety of the patient population.
Rationale: Exclusion #19 (previously #20)
– Provided clarification which maintains 
syncopal episode within 12 months of 
registration as an exclusionary criteria; however, 
this excludes episodes of vasovagal etiology.
Rationale: Exclusion #22 (previously #23)
– Provided clarification. Patients may 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 9
Document
Version Date
Summary of Changes and Rationale
participate in the follow-up status of a research 
study, provided no interventional drug(s), 
treatment or non-drug treatment is involved.
Rationale: (Pre-Secondary Hormones) Exclusion 
#28 (previously 29): removed entire exclusion 
criteria “Metastasis to organ other than lymph 
nodes and/or bones.”  The change does not effect 
the safety of the patient population.
Rationale: (Post-Secondary Hormones) Previous 
Exclusion #38 – removed.  The removal of this 
exclusion criteria does not effect the safety of the 
patient population.
•
Change: Section 1.3 PF-06753512 – ‘Four 
cohorts in Part A will evaluate escalating doses 
of an anti-programmed cell death protein 
1 (PD-1) antibody, PF-06801591, given SC in 
conjunction with each immunization at a site 
local to the vaccine vector delivery site.’
Rationale: Administrative change to correct a 
typographical error.
 
 
 
Rationale: The Prostate Cancer Clinical Trials 
Working Group 3 (PCWG3) is an international 
working group of clinical and translational 
experts in prostate cancer that convened in 
June 2012 and worked through February 2015 to 
update the recommendations of PCWG2 in light 
of a changing therapeutic landscape.40
Section 3.1 Study Overview – Figure 1 Study 
Schema: 
•
Change: Provided clarification on an 
intermediate dose level (Cohort 6.5A). Added 
‘If in Cohort 6A the tremelimumab 80 mg dose 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 10
Document
Version Date
Summary of Changes and Rationale
level is not well tolerated, enrollment may switch 
to Cohort 6.5A where patients will receive 
Adenovirus 6 x 1011VP + pDNA 5 mg 
+ tremelimumab 40 mg + PF-06801591 300 mg.  
If 80 mg tremelimumab is well tolerated in 
Cohort 6A, enrollment will proceed to Cohort 7A 
as shown in Figure 1.’
Rationale: Protocol allows for an intermediate 
dose for each component that may be evaluated 
if the side effect profile of the highest dose level 
is unfavorable.  Therefore, additional cohorts 
than those depicted in Figure 1 may be 
evaluated.  

Administrative Changes include:

Typographical error corrections.

Updating the Prostate Cancer Working 
Group 2 to the updated modified PCWG3
– see Appendix 5.
Amendment 5
17 August 2017
The reasons for Amendment 5 include:

Addition of testing for acetylcholine receptor 
(AChR) antibodies at screening.  In addition, 
samples are to be drawn for central evaluation 
upon suspicion of potential myasthenia gravis 
(MG) – Schedule of Activities, Section 7.1.6.
Rationale – Additional evaluation included to 
exclude patients who test positive at screening as 
agreed with FDA and to confirm requirement for 
evaluation if myasthenia gravis is suspected.

Inclusion of requirement for a neurologic 
examination as part of the Screening physical 
examination (PE) as well as all abbreviated PEs 
during Cycle 1 – Schedule of Activities and 
Section 7.1.3.
Rationale – Neurologic examination is required 
to ensure adequate assessment for underlying 
autoimmune disorders at baseline and occurrence 
of adverse events during the study treatment.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 11
Document
Version Date
Summary of Changes and Rationale
•
Addition of requirement to inform patients of the 
potential occurrence of immune related adverse 
events as part of the informed consent process as 
well providing patients with a Patient 
Information Card. – Schedule of Activities.
Rationale – Additional instructions added to 
ensure patients are aware of the potential side 
effects that may be experienced after receiving 
the study treatment.
•
Clarification that more than 15 patients may be 
enrolled in any of the expansion cohorts
– Sections 3.1 and 9.3.
Rationale – Patients who do not receive a 
minimum number of doses or who experience 
more than a two week interruption in dosing for 
any reason may be replaced to ensure adequate 
evaluation of the endpoints can be conducted.
•
Update to Overall Study Design – Figure 1 and 
Sections 3.1, 3.4, 7.1.2, 7.2.3, 7.5.1, 7.5.2 and 
9.6.1.3.
Rationale – Inclusion of Cohort 9A and 
clarification that cohorts with dose combinations 
other than those depicted in the figure may be 
evaluated.
•
Revision to exclusion criteria #12 – Section 4.2.
Rationale – Criteria revised to further clarify the 
exclusion for patients with history of or active
autoimmune disorders.
•
Addition of exclusion criteria #13 which includes 
exclusion for positive AChR antibodies and/or 
abnormal neurologic examination at screening 
indicating possible MG – Section 4.2.
Rationale – Additional exclusion criteria has 
been included as agreed upon with the FDA.
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 12
Document
Version Date
Summary of Changes and Rationale
•
Inclusion of definitions for the pharmacokinetic 
(PK) and immunogenicity analysis sets –
Section 9.1.
Rationale – As PK and immunogenicity 
assessments are a secondary endpoint, the 
population of patients who will be evaluated for 
these analyses has been included.
•
Revisions to the recommended management 
algorithms for liver, skin, neural, endocrine, 
renal or pulmonary toxicity/pathology, and 
diarrhea or colitis – Appendix 7.
Rationale – Section updated to tabular format for 
consistency in guidance used across other 
checkpoint inhibitor programs at Pfizer.
•
Inclusion of a recommended management 
algorithm for myasthenia gravis – Appendix 7.
Rationale – Algorithm included to provide 
investigators with guidance for the treatment of 
an adverse event observed in this study.
•
Administrative changes – Sections 3.1 and 5.1, 
5.4, 5.4.3.2, Appendix 1.
Rationale – Administrative changes.
Amendment 4
06 April 2017
The reasons for Amendment 4 include:
•
Inclusion of an additional cohort in the dose 
expansion phase, Cohort 5B, to include the 
evaluation of VBIR with PF-06801591 in the 
biochemically relapsed patients. – Schedule of 
Activities, Sections 1.3, 3.1, 3.1.2, 7.1.2, 7.5.1, 
7.5.2, 9.3, and Figure 1.
Rationale: Given the potential benefit of adding 
PF-06801591 with PrCa VBIR, the combination 
will be evaluated in the biochemically relapsed 
patient population after the safety has been 
established in the more advanced patient 
population.
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 13
Document
Version Date
Summary of Changes and Rationale
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•
Inclusion of a -7 day window for screening 
tumor assessments. – Schedule of Activities.
Rationale – Additional time allowed to provide 
flexibility in scheduling.
•
Tumor assessment to be performed every 
8 weeks (±5 days) – Schedule of Activities.
Rationale – Timeframe revised for consistency in 
collection time across all sites.
 
 
 
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 14
Document
Version Date
Summary of Changes and Rationale
assessment.

Inclusion of additional blood samples for 
tremelimumab and PF-06801591 PK evaluation. 
– Schedule of Activities.
Rationale: Additional sampling included to allow 
for evaluation of the steady state trough 
concentrations of tremelimumab and 
PF-06801591.

Inclusion of a Month 9 dosing visit in the 
Maintenance Period for Cohorts 6A through 
8A and Cohorts 2B, 3B and 5B.
– Schedule of Activities.
Rationale: Protocol correction as the 
PF-06801591 should continue to be administered 
monthly in the Maintenance Period.  Therefore, 
patients in these cohorts should return to the 
clinic for Month 9 to receive PF-06801591.

Update to the starting dose of PF-06801591 to 
130 mg. – Sections 1.6.6 and 5.4.3.4.
Rationale: Starting dose rounded for ease of 
bilateral administrations.

Inclusion of clarification that tremelimumab dose 
levels below the starting dose listed may be 
evaluated based on emerging safety data for 
tremelimumab and PF-06801591. – Section 3.1, 
5.4.3.4 and Table 4.
Rationale: Clarification added to allow for 
possibility of lower tremelimumab doses if 
needed.

Requirements for contraception revised from 
28 to 90 days. – Sections 4.1.2 and 4.3.
Rationale: Timeframe for required contraception 
increased to ensure adequate coverage of the 
monoclonal antibodies to be administered.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 15
Document
Version Date
Summary of Changes and Rationale

Post-secondary hormone patients are required to 
have only one of the three criteria listed in the 
inclusion criteria in order to be included.
– Section 4.1.3.
Rationale: Criteria revised to allow for more 
patients to be considered for inclusion in the 
study without impacting the safety or scientific 
value of the trial.

Clarification on the timepoint at which several 
entry criteria must be met included. –
Section 4.2 and 4.2.1.
Rationale: Administrative clarification.

Required washout for abiraterone changed to 
2 weeks from first dose. – Section 4.2.
Rationale – Given the short half-life of the 
compound, two weeks is sufficient for a washout 
prior to initiating treatment in this study.

Blood pressure limits changed to 160/100 mmHg 
despite optimal medical therapy – Section 4.2.
Rationale – Criteria revised to allow for more 
patients to be considered for inclusion in the 
study given the target patient populations.

Inclusion of the lower abdomen as an injection 
site for tremelimumab – Section 5.4.
Rationale – Additional injection site included for 
ease of administration.

Editorial and administrative changes
– Sections 2.2, 3.1.2, 7.4, 9.6.1, 9.6.4 and 
Appendix 3.
Rationale: Administrative changes and 
corrections.
Amendment 3
08 September 
The reasons for Amendment 3 include:

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 16
Document
Version Date
Summary of Changes and Rationale
2016
•
Inclusion of Cohorts 6A through 8A in Part A to 
evaluate escalating doses of PF-06801591 in 
combination with PrCa VBIR.  In addition, 
Cohorts 2B and 3B will be modified to evaluate 
the selected doses in Part B.  – Schedule of 
Activities including new tables to include 
assessments for these cohorts, Sections 1.3, 
1.3.1, 1.4.2, 1.6.6, 2.1, 2.2, 3.1, 3.1.1, 3.1.2, 
3.1.3, 3.2, 3.4, 5.1, 5.2, 5.3, 5.3.1, 5.3.2, 5.4, 
5.4.2, 5.4.3.4, 5.5, 5.7.4, 5.7.8, 7.1.2, 7.2.3, 7.5.2, 
9.2.1, 9.3, 9.6.1.3, 9.6.2 and 16, Figure 1, 
Removal of Table 1 and inclusion of 
Appendix 7.
Rationale: Pre-clinical studies indicate the 
efficacy of the PrCa VBIR may be increased 
when given in combination with an 
anti-PD-1 antibody.
•
Update to visit names in the Maintenance 
Treatment Period – Schedule of Activities.
Rationale – Administrative correction.
•
Inclusion of tremelimumab PK and ADA 
assessments in the Maintenance Treatment
Period – Schedule of Activities.
Rationale – Assessment included to allow for 
continued evaluation with additional dosing and 
administrative change.
 
 
 
 
Rationale – Less frequent assessment is 
considered sufficient for evaluation of the 
relevant study endpoints.  Therefore, the 
sampling has been reduced to limit the blood 
draws required by the patients.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 17
Document
Version Date
Summary of Changes and Rationale

Clarification on when sunitinib can be taken on 
study visit days. – Schedule of Activities.
Rationale – Administrative clarification.

Clarification a month is 28 days for the 
Maintenance Treatment Period schedule. –
Schedule of Activities.
Rationale – Administrative clarification.

Clarification that enrollment in Cohort 2B may 
be delayed – Sections 3.1 and 3.1.2.
Rationale – Enrollment of pre-secondary 
hormone patients may be delayed to allow for
adequate assessment of the safety of PrCa VBIR 
when given in combination with PF-06801591 in 
the post-secondary hormone population.

Clarification that intermediate dose cohorts or 
cohorts with lower treatment intensity compared 
to cohorts with an acceptable safety profile may 
be evaluated. – Section 3.1.
Rationale – Administrative clarification.

Revisions to the inclusion and exclusion criteria 
for biochemical relapse patients –
Sections 4.1.2 and 4.2.2.
Rationale – Criteria revised to more clearly 
define the desired patients to be included.

Additional exclusion criteria included for 
pre-secondary and post-secondary hormone 
patients – Sections 4.2.1 and 4.2.3.
Rationale – Additional criteria included to more 
accurately define the desired patient population.

Requirement for at least approximately 30% of 
post-secondary hormone patients to have 
measurable disease per RECIST v1.1 with the 
exception of metastases to the liver and for 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 18
Document
Version Date
Summary of Changes and Rationale
patients to have both PSA progression and 
measurable disease on imaging assessments
– Section 4.1.3.
Rationale – These patients will be included to 
allow for a higher chance to observe objective 
responses according to RECIST.

Additional instructions on how to calculate PSA 
doubling time included. – Sections 4.1.2, 
4.2.1 and 4.2.3.
Rationale – Additional instructions included to 
ensure consistency in the assessment across all 
sites.

Clarification on allowed prior use of ADT
– Section 4.2.2.
Rationale – Revised to ensure a more 
homogenous patient population across all study 
sites.

The vastus lateralis muscle is the preferred site 
of injection when possible rather than the deltoid 
muscle. – Section 5.4.
Rationale – Given the prevalence of disease in 
the pelvic lymph nodes, the vastus lateralis 
muscle is the preferred site of injection to allow 
for drainage to lymph nodes where disease may 
be present in a higher number of patients.

Additional information included on the preferred 
injection site for tremelimumab – Section 5.4.
Rationale – Administrative clarification.

New section provided to cover tremelimumab 
dose reductions and interruptions and to include 
additional criteria for patients who receive PrCa 
VBIR in combination with PF-06801591
– Sections 5.4.3.1 and 5.3.4.2.
Rationale – Given the known side effects 
observed with other anti-CTLA4 and 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 19
Document
Version Date
Summary of Changes and Rationale
anti-PD-1 antibodies, additional instructions 
have been included to address some of the side 
effects seen when these two class of agents are 
combined.
•
Inclusion of additional evaluations for potential 
Hy’s Law cases - Section 7.1.2.
Rationale – Additional assessments added for 
more thorough evaluation.
•
Clarification on when baseline central nervous 
system (CNS) imaging is required.
– Section 7.4.
Rationale – Administrative clarification.
•
Clarification that patients must receive at least 
80% of their planned dose of a component to be 
evaluated for the MTD determination.
– Section 9.1.
Rationale – Administrative clarification.
•
Clarification that lower doses than those with an 
acceptable safety profile may be evaluated.
– Section 9.2.1.
Rationale – Administrative clarification.
•
Clarification responses are not required to be 
confirmed – Appendix 4.
 
 
•
Administrative changes. – Schedule of 
Activities, Sections 1.3, 1.4.2, 2.1, 3.1.3, 5.1, 
5.3, 5.4, 5.4.3.1, 7.1.2, 7.1.3,7.1.5, 7.4, 9.6.4, 
Table 9 and Appendix 1.
Amendment 2
24 March 2016
The reasons for Amendment 2 include:
•
Inclusion of a Maintenance Treatment Period to 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 20
Document
Version Date
Summary of Changes and Rationale
outline dosing frequency and assessments to be 
performed post Cycle 2 – Schedule of Activities, 
Sections 3.1, 3.1.3, 5.4 and 6.2.
Rationale: Pre-clinical data indicates 
maintenance boost vaccinations with pDNA (and 
tremelimumab if the patient is assigned to 
receive tremelimumab) are effective to maintain 
the T cell response.
•
Window for collection of tumor assessments 
increased to every 8-12 weeks – Schedule of 
Activities Section. 
Rationale: Revised to more accurately reflect the 
standard of care imaging interval for patients.
•
Clarification on the pre-secondary hormone 
patients to be enrolled by removing references to 
M1. – Section 1.2, 3, 4.1.1, 4.2.1.
Rationale: Update to ensure the population 
described throughout the document is consistent 
with the inclusion criteria.
•
Clarification that patients for whom treatment 
with any secondary hormone has failed, not just 
abiraterone or enzalutamide, are considered to 
have met the post-secondary hormone patient 
population definition – Section 1.2, 3.1, 4.1.3, 
4.2.3.
Rationale: Based on emerging treatment options 
for patients with prostate cancer, the protocol has 
been revised to appropriately define this patient 
population.
 
Rationale: Administrative change.
 
 
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 21
Document
Version Date
Summary of Changes and Rationale
 
 
•
Study revised to allow post-secondary hormone 
patients to be enrolled in the dose escalation 
portion of the study – Section 3.
Rationale: Allowing patients with more 
advanced disease will not impact the assessment
of the safety of PrCa VBIR and will make the 
dose escalation available to more potential 
patients.
•
Study schematics and overall design revised to 
separate the study in to dose escalation and dose 
expansion portions – Sections 3.1, 3.2, 3.4, 9.1, 
9.3.
Rationale: Updated to simplify the schematic and 
description of the study design.
•
Minimum PSA threshold removed for patients 
enrolled in Part A of the study
– Section 4.1.1 and 4.1.3.
Rationale: Criteria revised to allow for additional 
patients to be considered during dose escalation.  
A minimum PSA level is not required to 
adequately assess the safety of the study 
treatments.
•
Update to exclusion criteria for prior 
chemotherapy.  The criteria previously listed 
under post-secondary hormone patients has been 
moved to the criteria for all patients
– Section 4.2.
Rationale: Allowance for prior chemotherapy in 
the hormone sensitive setting applies to 
pre-secondary hormone patients as well as 
post-secondary hormone patients.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 22
Document
Version Date
Summary of Changes and Rationale

Clarification that the analyses of Adverse Events 
is the primary analysis – Section 9.5.1.
Rationale: Administrative Clarification.

Temporal collection added as an appropriate way 
to collect temperature – Schedule of Activities 
and Section 7.1.3.
Rationale: Administrative clarification.

Window for collection of timed sampling added 
– Sections 7.2.1 and 7.2.2.
Rationale: Administrative Clarification.

Administrative edits – Schedule of Activities, 
Appendix 3 and 4.
Rationale: Administrative edits.
Amendment 1
02 October 2015
The reasons for Amendment 1 include:

Inclusion of an additional 6 months of follow-up 
after the last dose of study treatment – Schedule 
of Activities, Sections 3.1, 6.3 and 8.2.
Rationale – Additional follow-up included to 
allow for continued observation of patients to 
better characterize duration of potential treatment 
effect.

Removal of Day 99 visit from Cycle 1
– Schedule of Activities.
Rationale – Assessments from this visit were 
moved to either the Cycle 1 Day 85 or Cycle 
2 Day 1 visit to reduce the number of visits
required for the patients.

Addition of collection of baseline Gleason score 
– Schedule of Activities and Section 7.7.1.
Rationale – Inadvertent exclusion from prior 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 23
Document
Version Date
Summary of Changes and Rationale
protocol version.

Inclusion of instructions for calculation of visit 
windows – Schedule of Activities.
Rationale – Clarification. 

Inclusion of additional ECG, MUGA and 
creatinine clearance evaluations in Cohort 7
– Schedule of Activities for Cohort 7 and 
Section 7.1.2.
Rationale – Additional assessments added given 
the known toxicities of sunitinib.

Inclusion of language indicating historical PSA 
and imaging assessments may be requested
– Schedule of Activities and Section 7.4.
Rationale – Historical disease information may 
be collected to allow for assessment of the 
disease history.

Guidance provided should QTc prolongation be 
observed for patients dosed in Cohort 7
– Schedule of Activities for Cohort 7 and 
Section 7.1.4.
Rationale – Additional language added given the 
known toxicities of sunitinib.

Additional background information included
– Section 1.2, 1.3 and 1.6.1.
Rationale – Editorial changes.

Revisions to the primary objective and endpoint 
of the study – Sections 2.1 and 2.2.
Rationale – Additional objectives included to 
provide more clarity on the safety objective of 
the study.

Inclusion of evaluation of prostate cancer using 
irRECIST criteria rather than irRC
– Sections 2.2, 6.4, 7.4, 9.4 and Appendix 4.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 24
Document
Version Date
Summary of Changes and Rationale
Rationale – Recent published articles indicate 
irRECIST may be a more reliable and convenient 
method for evaluating disease status following 
treatment with immunotherapy products.

Revision of the definition of biochemically 
relapsed – Sections 3.1 and 4.1.2.
Rationale – Definition updated to more 
accurately reflect the intended patient population 
to be enrolled.

Revisions to the DLT criteria and clarification 
that patients who experience a DLT should be 
removed from study treatment– Sections 3.2 and 
6.4.
Rationale – DLT criteria revised to include 
definitions more appropriate for the treatment 
being administered and the anticipated safety 
profile of those compounds.

Inclusion of section on late onset toxicities
– Section 3.3.
Rationale – Additional information added to 
clarify how the study would be impacted with the 
observation of toxicity meeting the DLT criteria 
after the DLT observation period.

Revision to inclusion criteria – Sections 4.1.1
and 4.1.3.
Rationale – clarification that patients who have 
local recurrence of disease would be eligible for 
study participation and clarification on definition 
for measurable disease.

Revisions to dose modifications for adenovirus, 
tremelimumab and sunitinib – Table 4 and 
Table 5.
Rationale – Revised to require discontinuation of 
treatment should Grade 4 events occur given the 
expected safety profile of the compounds being 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 25
Document
Version Date
Summary of Changes and Rationale
administered.

Inclusion of instructions regarding concurrent 
treatment with denosumab or bisphosphates
– Section 5.7.3.
Rationale – Clarification. 

Inclusion of amylase and lipase in the required 
blood chemistry panel – Schedule of Activities, 
Section 7.1.2.
Rationale – Analytes added to adequately 
monitor the safety of the patients.

Inclusion of instructions for inclusion of lymph 
nodes in disease assessments and evaluation of 
bone scans – Section 7.4 and Appendix 5.
Rationale – Updated to provide additional 
instructions consistent with the PCWG2 as well 
as instruction on not including the use of certain 
lymph nodes in disease assessments given the 
mechanism of action for the PrCa VBIR.

Administrative changes or corrections
– Schedule of Activities and Sections 3.1, 5.4, 
5.7.2, 7.1.2, 8.14.3, 9.1, 9.3, 9.5.3, 16.
Original 
protocol
31 March 2015
Not Applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 26
SCHEDULE OF ACTIVITIES
SCHEDULE OF ACTIVITIES FOR DOSE EXPANSION COHORTS:

3B (mCRPC: PrCa VBIR (80 mg tremelimumab +300 mg PF-06801591);

5B (as of Amendment 7) (BCR: PrCa VBIR +80 mg treme +130 mg PF-06801591); and
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the ASSESSMENTS section of 
the protocol for detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the well-being of the participant.
Protocol Activity
Screen1
(28 days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment28
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 129
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
1
2
2
2
4
2
4
2
2
2
2
2
4
4
4
4
Informed consent2
X
Tumor history3
X
Medical history4
X
Complete physical 
examination5
X
X
Abbreviated physical 
examination5
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment of skin 
thickness at 
administration sites
X
Height
X
Weight
X
X
X
X
Vital signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Performance status7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Gleason score8
X

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 27
Protocol Activity
Screen1
(≤28 days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment28
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 129
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
Laboratory
Unique Screening 
Labs9
X
Hematology10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation12
X
X
X
X
X
X
X
Cardiac Troponin-I 
(cTnI) 1513
X
X
X
X
X
X
Urinalysis14
X
X
X
X
X
X
X
X
X
X
X
(12 lead) ECG15
X
X
X
X
ECHO or MUGA
X
X
Registration 
Registration16
X
Study Treatment
Adenovirus 
administration17
Refer to Schedule of Study Treatment, Pharmacokinetics and Tremelimumab and PF-06801591 Immunogenicity Assessments
Plasmid DNA 
administration17
Tremelimumab 
administration17
PF-06801591 
administration17
Tumor Assessment
CT scan, MRI scan or 
bone scan18
X
X18
Other samplings
 
AChR antibody20
X
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 28
Protocol Activity
Screen1
(≤28 days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment28
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 129
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
 
X
Pharmacokinetics and 
Tremelimumab ADA
Refer to Schedule of Study Treatment, Pharmacokinetics and Tremelimumab and PF-06801591 Immunogenicity Assessments
Pharmacokinetics and 
PF-06801591 ADA
Other clinical 
assessments
AEs26
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications and non-
drug supportive 
interventions27
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
* Visit windows during the treatment period are to be calculated based on the previous dosing visit.
Abbreviations: AChR = acetylcholine receptor; ADA = anti-drug antibodies; AEs = adverse events; CT = computed tomography; 
 
ECG = electrocardiogram; ECHO = echocardiogram; 
; MRI = magnetic resonance imaging; MUGA = multigated acquisition scan; 
1.
Screening: To be obtained within 28 days prior to study entry. 
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be collected more than 28 days prior to study entry.  As part of the consenting 
process, participants will be informed of the potential occurrence of immune related adverse events and will be provided with a Patient Information Card.
3.
Tumor History: Will be collected within 28 days prior to study entry.  Includes details of primary diagnosis and treatment history.  If available, historical PSA results and 
imaging assessments (eg, CT scans, MRIs or bone scans) may also be requested.
4.
Medical History: Includes history of disease process other than prostate cancer (active or resolved) and significant concurrent illness.  Includes prior treatments and any 
current medical treatment for any condition.
5.
Complete and abbreviated physical examinations: A neurologic examination must be conducted at Screening to look for potential signs suggestive of autoimmune 
disorders.  In addition, all abbreviated physical examinations conducted during Cycle 1 must include a neurologic examination.
6.
Vital signs: Includes temperature and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  
7.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
8.
Gleason score: The Gleason score at the time of initial diagnosis and/or time of most current recurrence should be collected.
CCI
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 29
9.
Unique Screening Labs: To include hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV).  Samples will be 
analyzed locally.
10. Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.  If baseline assessment 
was performed within 72 hours of Cycle 1 Day 1, repeat is not required. Samples will be analyzed locally.  
11. Blood Chemistry: Should include sodium, potassium, chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, calcium, magnesium, 
phosphorus, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, amylase, lipase, and 
.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, repeat is not required. Samples will be analyzed locally. 
12. Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally. 
13.
Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 28 days before study entry, preferably using the central laboratory kits provided. See Section 7.1.7 for full details.
14. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
15. Triplicate 12 leads ECGs: At each time point, three consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the 
mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs may be 
performed as clinically indicated. 
16. Registration: Participant number and dose level allocation operated by Pfizer Inc.
17. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.
18. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Screening images may be obtained within 5 weeks of registration.  Imaging 
obtained as part of standard of care but within 28 days (-7 days) of registration may be used for screening assessment.  Imaging may include chest, abdomen and pelvis CT or 
MRI scans or bone scans.  Bone scans will be performed at baseline if disease is suspected and on-study as appropriate to follow disease.  Baseline central nervous system 
(CNS) imaging is not required with the exception of symptomatic participants to rule out CNS metastases.  CT or MRI scans, as well as bone scans, when indicated, are to be 
done every 8 weeks (±5 days) with the first one to occur 8 weeks after C1D1 until disease progression that requires new treatment modality, permanent discontinuation, or 
death.  Disease progression will be confirmed with two consecutive timepoints at least 4-6 weeks apart in the absence of rapid clinical deterioration.  Tumor assessment
should be repeated at the End of Treatment visit if more than 6 weeks have passed since the last evaluation.  
 
 
 
 
20. Acetylcholine receptor (AChR) antibody: Sample to be sent to the central laboratory for analysis. 
 
 Treatment decisions will be made based on the clinical diagnosis.
  
 
 
 
 
 
CCI
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 30
26. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTC AE) version 4.03.  Participants must be followed for AEs for 6 months after the last study treatment administration or until all drug related 
toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  For serious adverse events 
(SAEs), the active reporting period to Pfizer or its designated representative begins from the time that the participant provides informed consent, which is obtained prior to the 
participant’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through and including the 6 month 
follow-up period.  Serious adverse events occurring after the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at 
a minimum, all serious adverse events that the investigator believes have at least a reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
27. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
28. End of Treatment Visit: The End of treatment visit will be completed at the timepoint when a decision is made to discontinue study treatment.  This can occur during 
Cycles 1 or 2 or during the Maintenance Treatment Phase of the study.  Obtain these assessments if not completed in the past two weeks (past 6 weeks for tumor assessments).
29. Follow up: At least 28 days, and no more than 35 days after discontinuation of study treatment, participants will return to complete the required assessments.  Participants will 
then return at Month 2, Month 4 and Month 6 to complete the required assessments.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 31
SCHEDULE OF ACTIVITIES FOR DOSE ESCALATION (Amendment 6); COHORTS 1A THROUGH 4A, COHORTS 6A 
THROUGH 9A AND DOSE EXPANSION COHORTS 1B THROUGH 3B AND 5B –
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the ASSESSMENTS section of 
the protocol for detailed information on each assessment required for compliance with the protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the well-being of the participant.
Protocol Activity
Screen1
(28
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment27
Follow- Up
(Months after EOT visit)
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 128
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
1
2
2
2
4
2
4
2
2
2
2
2
4
4
4
4
Informed consent2
X
Tumor history3
X
Medical history4
X
Complete physical 
examination5
X
X
Abbreviated physical 
examination5
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment of skin 
thickness at 
administration sites
X
Height
X
Weight
X
X
X
X
Vital signs6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Performance status7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Gleason score8
X
Laboratory
Unique Screening 
Labs9
X
Hematology10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation12
X
X
X
X
X
X
X
Urinalysis13
X
X
X
X
X
X
X
X
X
X
X

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 32
Protocol Activity
Screen1
(≤28
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment27
Follow- Up
(Months after EOT visit)
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 128
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
(12 lead) ECG14
X
X
X
X
ECHO or MUGA
X
X
Registration 
Registration15
X
Study Treatment
Adenovirus 
administration16
Refer to Schedule of Study Treatment, Pharmacokinetics and Tremelimumab and PF-06801591 Immunogenicity Assessments
Plasmid DNA 
administration16
Tremelimumab 
administration –
Starting at Cohort 3A16
PF-06801591
administration –
Starting at Cohort 6A16
Tumor Assessment
CT scan, MRI scan or 
bone scan17
X
X17
Other samplings
 
AChR antibody19
X
 
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 33
Protocol Activity
Screen1
(≤28
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment27
Follow- Up
(Months after EOT visit)
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 128
Month 2
Month 4
Month 6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35
days
Visit Window (Days)
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
Pharmacokinetics and 
Tremelimumab ADA
Refer to Schedule of Study Treatment, Pharmacokinetics and Tremelimumab and PF-06801591 Immunogenicity Assessments Table
Pharmacokinetics and 
PF-06801591 ADA
Other clinical 
assessments
AEs25
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications and 
non-drug supportive 
interventions26
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
* Visit windows during the treatment period are to be calculated based on the previous dosing visit.
Abbreviations: AChR = acetylcholine receptor; ADA = anti-drug antibodies; AEs = adverse events; CT = computed tomography; 
 
ECG = electrocardiogram; ECHO = echocardiogram;
 cell; MRI = magnetic resonance imaging; MUGA = multigated acquisition scan; 
1.
Screening: To be obtained within 28 days prior to study entry.
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be collected more than 28 days prior to study entry.  As part of the consenting 
process, participants will be informed of the potential occurrence of immune related adverse events and will be provided with a Patient Information Card.
3.
Tumor History: Will be collected within 28 days prior to study entry.  Includes details of primary diagnosis and treatment history.  If available, historical PSA results and 
imaging assessments (eg, CT scans, MRIs or bone scans) may also be requested.
4.
Medical History: Includes history of disease process other than prostate cancer (active or resolved) and significant concurrent illness.  Includes prior treatments and any 
current medical treatment for any condition.
5.
Complete and abbreviated physical examinations: A neurologic examination must be conducted at Screening to look for potential signs suggestive of autoimmune 
disorders.  In addition, all abbreviated physical examinations conducted during Cycle 1 must include a neurologic examination.
6.
Vital signs: Includes temperature and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  
7.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
8.
Gleason score: The Gleason score at the time of initial diagnosis and/or time of most current recurrence should be collected.
9.
Unique Screening Labs: To include hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV).  Samples will be 
analyzed locally.
10. Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils. If baseline assessment 
was performed within 72 hours of Cycle 1 Day 1, repeat is not required. Samples will be analyzed locally.  
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 34
11. Blood Chemistry: Should include sodium, potassium, chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, calcium, magnesium, 
phosphorus, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, amylase, lipase, and 
.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, repeat is not required. Samples will be analyzed locally.  
12. Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT). Samples will be analyzed locally.
13. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
14. Triplicate 12 leads ECGs: At each time point, three consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the 
mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs may be 
performed as clinically indicated. 
15. Registration: Participant number and dose level allocation operated by Pfizer Inc.
16. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.
17. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Screening images may be obtained within 5 weeks of registration.  Imaging 
obtained as part of standard of care but within 28 days (-7 days) of registration may be used for screening assessment.  Imaging may include chest, abdomen and pelvis CT or 
MRI scans or bone scans.  Bone scans will be performed at baseline if disease is suspected and on-study as appropriate to follow disease.  Baseline central nervous system 
(CNS) imaging is not required with the exception of symptomatic participants to rule out CNS metastases.  CT or MRI scans, as well as bone scans, when indicated, are to be 
done every 8 weeks (±5 days) with the first one to occur 8 weeks after C1D1 until disease progression that requires new treatment modality, permanent discontinuation, or 
death.  Disease progression will be confirmed with two consecutive timepoints at least 4-6 weeks apart in the absence of rapid clinical deterioration.  Tumor assessment 
should be repeated at the End of Treatment visit if more than 6 weeks have passed since the last evaluation. 
 
 
 
 
19. Acetylcholine receptor (AChR) antibody: Sample to be sent to the central laboratory for analysis. 
 
  Treatment decisions will be made based on the clinical diagnosis.
20. Circulating Tumor Cells: Approximately 10 mL of blood will be collected for evaluation of circulating tumor cells by the central laboratory.
21. Serology: Approximately 10 mL of blood will be collected for central evaluation of IgG antibody responses against the vaccine.  
22. Peripheral Blood Mononuclear Cells: Approximately 50 mL of blood will be collected for central evaluation of immune response. In addition, the samples may also be 
used for T cell receptor (TCR) sequencing analysis.
23. Myeloid Derived Suppressor Cells: Approximately 5 mL of blood will be collected for central evaluation of circulating MDSC.
24. Fresh Tumor Tissue Samples: In the dose escalation portion of the study and Cohort 2B in the dose expansion portion, optional biopsies can be performed at screening 
and/or Cycle 2 Day 1 (-21 days) at the discretion of the investigator and upon agreement from the participant.  Additional unscheduled on-treatment biopsies or biopsies at 
other timepoints may be collected, if indicated, and agreed upon by the sponsor and investigator and agreed to by the participant.  In the dose expansion Cohorts 3B and 4B, 
mandatory pre-treatment and on-treatment at Cycle 2 Day 1 (-21 days) biopsies will be obtained in at least approximately 5 participants in each cohort.  If the participant
discontinues study treatment before Cycle 2 Day 1, the biopsy can be performed as part of the End of Treatment visit.
25. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTC AE) version 4.03.  Participants must be followed for AEs for 6 months after the last study treatment administration or until all drug related 
toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  For serious adverse events 
(SAEs), the active reporting period to Pfizer or its designated representative begins from the time that the participant provides informed consent, which is obtained prior to the 
participant’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through and including the 6 month 
follow-up period.  Serious adverse events occurring after the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at 
a minimum, all serious adverse events that the investigator believes have at least a reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 35
26. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
27. End of Treatment Visit: The End of treatment visit will be completed at the timepoint when a decision is made to discontinue study treatment.  This can occur during 
Cycles 1 or 2 or during the Maintenance Treatment Phase of the study.  Obtain these assessments if not completed in the past two weeks (past 6 weeks for tumor assessments).
28. Follow up: At least 28 days, and no more than 35 days after discontinuation of study treatment, participants will return to complete the required assessments.  Participants will 
then return at Month 2, Month 4 and Month 6 to complete the required assessments.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 36
SCHEDULE OF ACTIVITIES FOR MAINTENANCE TREATMENT PERIOD (COHORT 1A AND 1B)
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 10
Month 12
Month 14
Month 16
Month 18
Month 20
Month 22 and every 
2 months thereafter
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
Abbreviated physical examination
X
X
X
X
X
X
X
Weight
X
X
Vital signs1
X
X
X
X
X
X
X
Performance status2
X
X
X
X
X
X
X
Laboratory
Hematology3
X
X
X
X
X
X
X
Blood Chemistry4
X
X
X
X
X
X
X
Coagulation5
X
X
X
X15
Urinalysis6
X
X
X
X15
(12 lead) ECG7
X
X
Study Treatment
Plasmid DNA Administration8
X
X
X
X
X
X
X
Tremelimumab administration –
Starting at Cohort 3A8
X
X
X
X
X
X
X
Tumor Assessment
CT scan, MRI scan or bone scan9
X9
Other Samplings
PK and Tremelimumab ADA –
Starting at Cohort 3A
X
X
X
X15
 
Other clinical assessments
AEs13
X
X
X
X
X
X
X
Concomitant medications and 
non-drug supportive interventions14
X
X
X
X
X
X
X
* When a decision is made to discontinue study treatment during the Maintenance Treatment Period, the End of Treatment visit assessments should be performed.  The participant
will then enter the Post Treatment Period of the study.
** Study visit is based on completion of two cycles in the treatment period.  Visit window for the first maintenance treatment visit is to be calculated based on the Cycle 2 Day 85 
dosing date.  The first dose in the maintenance period should occur 56 days after the C2D85 dosing date.  A month is defined as 28 days.
1.
Vital signs: Includes temperature and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  
2.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 37
3.
Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.  Samples will be 
analyzed locally.
4.
Blood Chemistry: Should include sodium, potassium, chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, calcium, magnesium, 
phosphorus, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, amylase, lipase, and 
  Samples will be analyzed locally.
5.
Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.
6.
Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
7.
Triplicate 12 leads ECGs: At each time point, three consecutive 12-lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the
mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs may be 
performed as clinically indicated.
8.
Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.  
9.
Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Imaging may include chest, abdomen and pelvis CT or MRI scans or bone scans.  
CT or MRI scans, as well as bone scans, when indicated, are to be done every 8 weeks (±5 days) until disease progression that requires new treatment modality, permanent 
discontinuation, or death.  Disease progression will be confirmed with two consecutive timepoints at least 4-6 weeks apart in the absence of rapid clinical deterioration. 
 
 
  
13. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTC AE) version 4.03.  Participants must be followed for AEs for 6 months after the last study treatment administration or until all drug related 
toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  For serious adverse events 
(SAEs), the active reporting period to Pfizer or its designated representative begins from the time that the participant provides informed consent, which is obtained prior to the 
participant’s participation in the study, ie, prior to undergoing any study-related procedure and/or receiving investigational product, through and including the 6 month 
follow-up period.  Serious adverse events occurring after the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at 
a minimum, all serious adverse events that the investigator believes have at least a reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
14. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
15. To be assessed every 4 months.
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 38
SCHEDULE OF ACTIVITIES FOR MAINTENANCE TREATMENT PERIOD (DOSE ESCALATION COHORTS 6A 
THROUGH 9A AND DOSE EXPANSION COHORTS 3B AND 5B)
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 
9
Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 
22 and 
every 
month 
thereafter
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Abbreviated physical examination
X
X
X
X
X
X
X1
Weight
X
X
Vital signs2
X
X
X
X
X
X
X1
Performance status3
X
X
X
X
X
X
X1
Laboratory
Hematology4
X
X
X
X
X
X
X1
Blood Chemistry5
X
X
X
X
X
X
X1
Coagulation6
X
X
X
X9
Cardiac Troponin-I (cTnI)7
X
X
Urinalysis8
X
X
X
X9
(12 lead) ECG10
X
X
Study Treatment
Plasmid DNA Administration11
X
X
X
X
X
X
X1
Tremelimumab administration11
X
X
X
X
X
X
X1
PF-06801591 administration11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tumor Assessment
CT scan, MRI scan or bone scan12
X12
Other Samplings
PK and Tremelimumab ADA
X
X
X
X9
PK and PF-06801591 ADA
X
X
X
X9
6
Other clinical assessments
AEs17
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications and 
non-drug supportive 
interventions18
X
X
X
X
X
X
X
X
X
X
X
X
X
X
* When a decision is made to discontinue study treatment during the Maintenance Treatment Period, the End of Treatment visit assessments should be performed.  The participant
will then enter the Post Treatment Period of the study.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 39
** Study visit is based on completion of two cycles in the treatment period.  Visit window for the first maintenance treatment visit is to be calculated based on the Cycle 2 Day 85 
dosing date.  The first dose in the maintenance period should occur 28 days after the C2D85 dosing date.  A month is defined as 28 days.
1.
To be assessed every 2 months.
2.
Vital signs: Includes temperature and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  
3.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
4.
Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.  Samples will be 
analyzed locally.
5.
Blood Chemistry: Should include sodium, potassium, chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, calcium, magnesium, 
phosphorus, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, amylase, lipase, and 
  Samples will be analyzed locally.
6.
Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.
7.
Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 28 days before study entry, preferably using the central laboratory kits provided. See Section 7.1.7 for full details.
8.
Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
9.
To be assessed every 4 months.
10. Triplicate 12 leads ECGs: At each time point, three consecutive 12 lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the 
mean QTcF is prolonged (>500 msec), the ECGs should be reevaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs may be performed 
as clinically indicated.
11. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.
12. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Imaging may include chest, abdomen and pelvis CT or MRI scans or bone scans.  
CT or MRI scans, as well as bone scans, when indicated, are to be done every 8 weeks (±5 days) until disease progression that requires new treatment modality, permanent 
discontinuation, or death.  Disease progression will be confirmed with two consecutive timepoints at least 4-6 weeks apart in the absence of rapid clinical deterioration. 
 
 
  
16. To be assessed every 6 months.
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 40
17. Adverse Event (AE) Assessments: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI CTC AE) version 4.03.  Participants must be followed for AEs for 6 months after the last study treatment administration or until all drug related 
toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  For serious adverse events 
(SAEs), the active reporting period to Pfizer or its designated representative begins from the time that the participant provides informed consent, which is obtained prior to the 
participant’s participation in the study, ie, prior to undergoing any study related procedure and/or receiving investigational product, through and including the 6 month follow 
up period.  Serious adverse events occurring after the active reporting period has ended should be reported to the sponsor if the investigator becomes aware of them; at a 
minimum, all serious adverse events that the investigator believes have at least a reasonable possibility of being related to investigational product are to be reported to the 
sponsor.
18. Concomitant Treatments: All concomitant medications and non drug supportive interventions should be recorded in the CRF.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 41
Schedule of Study Treatment – Cohorts 1A and 2A
Protocol Activity
Screen
(28 days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
Follow-
Up
Study Day
Day 
1
Day 
8
Day 15
Day 22
Day 29
Day 43
Day 57
Day 71
Day 85
Day 
113
Cycle Day
Day 1 Day 29 Day 57 Day 
85
Day 99
Visit Window 
(days)
1
2
2
2
4
2
4
2
2
2
2
2
4
Study Treatment
Adenovirus1
X
X
Plasmid DNA2
X
X
X
X
X
X
1.
Adenovirus will be administered intramuscularly on Day 1 of each cycle.
2.
Plasmid DNA vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 42
Schedule of Study Treatment, Pharmacokinetics, and Tremelimumab Immunogenicity Assessments – Cohort 3A
Protocol Activity
Screen
(28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of 
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
3 -6
Day
8
Day 15Day 22Day 29Day 43Day 57Day 71Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day
99
28-35 
days
Visit Window 
(hours)
24 hr 48 hr 48 hr
Visit Window 
(days)
2
4
2
4
2
2
2
2
2
4
4
4
4
Study Treatment
Adenovirus1
X
X
Plasmid DNA2
X
X
X
X
X
X
Tremelimumab3
X
X
X
X
X
X
X
X
Pharmacokinetics 
and 
Tremelimumab 
Immunogenicity
PK for 
tremelimumab4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ADA for 
tremelimumab5
X
X
X
X
X
X
X
X
Abbreviations: ADA = Anti-drug antibody.
1.
Adenovirus will be administered intramuscularly on Day 1 of each cycle.  Tremelimumab will be administered after the adenovirus. Both adenovirus injections should be 
administered prior to administering the tremelimumab.
2.
Plasmid DNA vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  Tremelimumab will be 
administered after the plasmid DNA.  Both pDNA vaccinations should be administered prior to administering the tremelimumab.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  Tremelimumab will be administered after the adenovirus or plasmid DNA.
4.
Blood samples for determination of tremelimumab drug concentrations will be collected at pre-dose (within 6 hrs prior to tremelimumab dose) on Day 1, any time between 
Day 3 to Day 6 (48 to 120 hr), Day 8 (168 hr 24 hours), Day 15 (336 hr 48 hours), and Day 22 (504 hr 48 hours) after the Day 1 tremelimumab dose; and additionally at 
pre-dose (within 6 hrs prior to tremelimumab dose) on Day 29, Day 57 and Day 85 of Cycle 1; at pre-dose (within 6 hrs prior to tremelimumab dose) on Day 1 and Day 29 of 
Cycle 2; at the End of Treatment (EOT) visit; and at 2, 4 and 6 months after EOT during the follow-up period.
5.
Blood samples for detection of anti-drug antibodies (ADA) against tremelimumab will be collected as outlined in the schedule of activities.  Samples to be collected on dosing 
days are to be obtained within 6 hours prior to tremelimumab dosing. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 43
Schedule of Study Treatment, Pharmacokinetics, Tremelimumab and PF-06801591 Immunogenicity Assessments –
Cohorts 6A through 9A
Protocol Activity
Screen
(28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of 
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
3 -6
Day
8
Day 15Day 22Day 29Day 43Day 57Day 71Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28-35 
days
Visit Window 
(hours)
24 hr 48 hr 48 hr
Visit Window 
(days)
2
4
2
4
2
2
2
2
2
4
4
4
4
Study Treatment
Adenovirus1
X
X
Plasmid DNA2
X
X
X
X
X
X
Tremelimumab3
X
X
X
X
X
X
X
X
PF-068015914
X
X
X
X
X
X
X
X
Pharmacokinetics 
and 
Tremelimumab 
Immunogenicity
PK for
tremelimumab5
X
X
X
X
X
X
X
X
X
X
ADA for 
tremelimumab5
X
X
X
X
X
X
X
X
PK for 
PF-068015916
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ADA for 
PF-068015917
X
X
X
X
X
X
X
X
Abbreviations: ADA = Anti-drug antibody.
1.
Adenovirus will be administered intramuscularly on Day 1 of each cycle.  Tremelimumab and PF-06801591 will be administered after the adenovirus.  Both adenovirus 
injections should be administered prior to administering the tremelimumab and PF-06801591.
2.
Plasmid DNA vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  Tremelimumab and 
PF-06801591 will be administered after the plasmid DNA.  Both pDNA vaccinations should be administered prior to administering the tremelimumab and PF-06801591.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  Tremelimumab will be administered after the adenovirus or plasmid DNA and before the PF-06801591.  Both tremelimumab injections should be 
administered prior to administering the PF-06801591.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 44
4.
PF-06801591 will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 
of each cycle.  PF-06801591 will be administered after the adenovirus or plasmid DNA and after the tremelimumab.
5.
Blood samples for determination of tremelimumab drug concentrations and for detection of ADA against tremelimumab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing.
6.
Blood samples for determination of PF-06801591 drug concentrations will be collected at pre-dose (within 6 hrs prior to PF-06801591 dose) on Day 1, any time between 
Day 3 to Day 6 (48 to 120 hr), Day 8 (168 hr 24 hours), Day 15 (336 hr 48 hours), and Day 22 (504 hr 48 hours) after the Day 1 PF-06801591 dose; and additionally at 
pre-dose (within 6 hrs prior to PF-06801591 dose) on Day 29, Day 57 and Day 85 of Cycle 1; at pre-dose (within 6 hrs prior to PF-06801591 dose) on Day 1 and Day 29 of 
Cycle 2; at the End of Treatment (EOT) visit; and at 2, 4 and 6 months after EOT during the follow-up period.
7.
Blood samples for detection of ADA against PF-06801591 will be collected as outlined in the schedule of activities. Samples to be collected on dosing days are to be 
obtained within 6 hours prior to PF-06801591 dosing.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 45
Schedule of Study Treatment, Pharmacokinetics, and Tremelimumab Immunogenicity Assessments – Expansion Cohort 1B 
Protocol Activity Screen1
(28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
8
Day 15 Day 22 Day 29 Day 43 Day 57 Day 71 Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 1 Day 
29
Day 
57
Day 
85
Day 
99
28-35 
days
Visit Window 
(hours)
24 hr 48 hr 48 hr
Visit Window 
(days)
2
4
2
4
2
2
2
2
2
4
4
4
4
Study Treatment
Adenovirus1
X
X
Plasmid DNA2
X
X
X
X
X
X
Tremelimumab3
X
X
X
X
X
X
X
X
Pharmacokinetic
s and 
Tremelimumab 
Immunogenicity
PK for
tremelimumab4
X
X
X
X
X
X
X
X
X
X
ADA for 
tremelimumab4
X
X
X
X
X
X
X
X
Abbreviations: ADA = Anti-drug antibody.
1.
Adenovirus will be administered intramuscularly on Day 1 of each cycle.  Tremelimumab will be administered after the adenovirus.  Both adenovirus injections should be
administered prior to administering the tremelimumab.
2.
Plasmid DNA vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  Tremelimumab will be 
administered after the plasmid DNA.  Both pDNA vaccinations should be administered prior to administering the tremelimumab.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  Tremelimumab will be administered after the adenovirus or plasmid DNA.
4.
Blood samples for determination of tremelimumab drug concentrations and for detection of ADA against tremelimumab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 46
Schedule of Study Treatment, Pharmacokinetics, and Immunogenicity Assessments – Expansion Cohorts, 3B and 5B
Protocol Activity
Screen
(28
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of 
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
8
Day 15 Day 22 Day 29 Day 43 Day 57 Day 71 Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 1 Day 
29
Day 
57
Day 
85
Day 
99
28-35 
days
Visit Window 
(hours)
24 hr 48 hr 48 hr
Visit Window 
(days)
2
4
2
4
2
2
2
2
2
4
4
4
4
Study Treatment
Adenovirus1
X
X
Plasmid DNA2
X
X
X
X
X
X
Tremelimumab3
X
X
X
X
X
X
X
X
PF-068015914
X
X
X
X
X
X
X
X
Pharmacokinetics 
and 
Tremelimumab
Immunogenicity
PK for 
tremelimumab5
X
X
X
X
X
X
X
X
X
X
ADA for
tremelimumab5
X
X
X
X
X
X
X
X
PK for 
PF-068015916
X
X
X
X
X
X
X
X
X
X
ADA for 
PF-068015916
X
X
X
X
X
X
X
X
Abbreviations: ADA = Anti-drug antibody.
1.
Adenovirus will be administered intramuscularly on Day 1 of each cycle.  Tremelimumab and PF-06801591 will be administered after the adenovirus.  Both adenovirus 
injections should be administered prior to administering the tremelimumab and PF-06801591.
2.
Plasmid DNA vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  Tremelimumab and 
PF-06801591 will be administered after the plasmid DNA.  Both pDNA vaccinations should be administered prior to administering the tremelimumab and PF-06801591.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  Tremelimumab will be administered after the adenovirus or plasmid DNA and before the PF-06801591.  Both tremelimumab injections should be 
administered prior to administering the PF-06801591.
4.
PF-06801591 will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 
of each cycle.  PF-06801591 will be administered after the adenovirus or plasmid DNA and after the tremelimumab.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 47
5.
Blood samples for determination of tremelimumab drug concentrations and for detection of ADA against tremelimumab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing.
6.
Blood samples for determination of PF-06801591 drug concentrations and for detection of ADA against PF-06801591 will be collected as outlined in the schedule of 
activities. Samples to be collected on dosing days are to be obtained within 6 hours prior to PF-06801591 dosing.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 48
TABLE OF CONTENTS
SCHEDULE OF ACTIVITIES................................................................................................26
LIST OF TABLES...................................................................................................................53
LIST OF FIGURES .................................................................................................................53
APPENDICES .........................................................................................................................53
1. INTRODUCTION ...............................................................................................................55
1.1. Mechanism of Action/Indication.............................................................................55
1.2. Background and Rationale ......................................................................................55
1.3. Overview of PrCa VBIR Regimen (PF-06753512) ................................................56
1.3.1. Rationale for the Components of PrCa VBIR ............................................58
1.3.2. Safety and Part B Expansion Dose for PF-06753512 (PrCa VBIR) 
combined with PF-06801591 (anti PD-L1 antibody) ......................................59
1.4. Nonclinical Safety...................................................................................................61
1.4.1. Nonclinical Toxicity Study for PrCa VBIR................................................61
1.4.2. Nonclinical Toxicity Studies of PrCa VBIR with PF-06801591................61
1.5. Pharmacokinetics of Tremelimumab and PF-06801591.........................................62
1.5.1. Tremelimumab Pharmacokinetics After Intravenous Administration........62
1.5.2. PF-06801591 Pharmacokinetics.................................................................63
1.6. Starting Dose Rationale...........................................................................................63
1.6.1. Clinical Adenovirus C68 Dosing................................................................63
1.6.2. Clinical Plasmid DNA Dosing....................................................................64
1.6.3. Clinical Tremelimumab Dosing .................................................................64
1.6.4. Clinical PF-06801591 Dosing ....................................................................64
1.6.4.1. PF-06801591, an Anti-PD-1 Antibody: Clinical 
Experience in Study B8011001 (NCT02573259) .............................65
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................66
2.1. Part A Objectives ....................................................................................................66
2.2. Part A Endpoints .....................................................................................................67
2.3. Part B Objectives and Endpoints.............................................................................69
3. STUDY DESIGN.................................................................................................................70
3.1. Study Overview.......................................................................................................70
3.1.1. Dose Escalation (Part A) ............................................................................71
3.1.2. Dose Expansion (Part B) ............................................................................72

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 49
3.1.3. Maintenance Treatment Period...................................................................73
3.2. DLT Definition........................................................................................................74
3.3. MTD Definition for Part A......................................................................................75
3.4. Part B Expansion Dose............................................................................................75
3.4.1. Part B Expansion Dose: Participants with mCRPC (Cohort 3B) ...............75
3.4.2. Part B Expansion Dose: Participants with Rising PSA at High Risk 
for Recurrence After Definitive Local Therapy (Biochemical Relapse or 
BCR) ................................................................................................................76
3.5. Declaration of RP2D ...............................................................................................76
4. PARTICIPANT SELECTION.............................................................................................76
4.1. Inclusion Criteria for All Participants .....................................................................76
4.1.1. Additional Inclusion Criteria for Participants with Rising PSA at 
High Risk for Recurrence After Definitive Local Therapy (Biochemical 
Relapse)............................................................................................................77
4.1.2. Additional Inclusion Criteria for Participants in Part B Expansion  
Cohort 3B - After Novel Hormone Treatment (enzalutamide or 
abiraterone) ......................................................................................................78
4.2. Exclusion Criteria for all Participants .....................................................................79
4.3. Lifestyle Guidelines ................................................................................................81
4.4. Sponsor’s Qualified Medical Personnel..................................................................82
5. STUDY TREATMENTS.....................................................................................................83
5.1. Allocation to Treatment ..........................................................................................83
5.2. Participant Compliance ...........................................................................................83
5.3. Investigational Product Supplies.............................................................................84
5.3.1. Dosage Form(s) and Packaging..................................................................84
5.3.2. Preparation and Dispensing........................................................................85
5.4. Administration.........................................................................................................85
5.4.1. Recommended Dose Modifications............................................................86
5.4.2. Dosing Interruptions/Delays.......................................................................86
5.4.3. Dosing Interruptions/Delays due to Non-Related Events...........................87
5.4.4. Dose Reductions .........................................................................................87
5.4.4.1. AdC68 Dose Reductions ...........................................................88
5.4.4.2. Tremelimumab Dose Reductions..............................................88
5.4.4.3. PF-06801591 Dose Reductions.................................................89

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 50
5.5. Investigational Product Storage ..............................................................................91
5.6. Investigational Product Accountability...................................................................92
5.6.1. Destruction of Investigational Product Supplies ........................................92
5.7. Concomitant Treatment(s).......................................................................................92
5.7.1. Prohibited Concomitant Vaccines ..............................................................93
5.7.2. Other Anti-tumor/Anti-cancer or Experimental Drugs...............................93
5.7.3. Participants on beta blockers ......................................................................93
5.7.4. Supportive Care ..........................................................................................93
5.7.5. Anti-Diarrhea and Anti-Emetic Therapy....................................................93
5.7.6. Anti-inflammatory Therapy........................................................................94
5.7.7. Therapy for Treatment of Pyrexia and Flu-like Symptoms........................94
5.7.8. Corticosteroids............................................................................................94
5.7.9. Surgery........................................................................................................94
6. STUDY PROCEDURES .....................................................................................................94
6.1. Screening.................................................................................................................94
6.2. Study Period ............................................................................................................94
6.3. Follow-up Period.....................................................................................................94
6.4. Patient Withdrawal..................................................................................................94
6.4.1. Withdrawal from Treatment .......................................................................95
6.4.2. Wtihdrawal from Study ..............................................................................95
7. ASSESSMENTS..................................................................................................................96
7.1. Safety Assessments .................................................................................................96
7.1.1. Adverse Events...........................................................................................96
7.1.2. Laboratory Safety Assessment ...................................................................96
7.1.3. Vital Signs, Physical Examination and Skin Assessment ..........................97
7.1.4. (12-Lead) ECG ...........................................................................................98
7.1.5. Monitoring for Potential Immune Mediated Endocrinopathies..................98
7.1.6. Acetylcholine Receptor Testing .................................................................99
7.1.7. Cardiac Safety Monitoring .........................................................................99
7.2. Pharmacokinetics Assessments.............................................................................100
7.2.1. Serum for Assessment of Tremelimumab Pharmacokinetics...................100
7.2.2. Serum for Assessment of PF-06801591 Pharmacokinetics......................101

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 51
............................................................................101
...........................................................................102
....................................................................................................102
...........................................................102
.........................................................................103
...........................................................................103
...............................................................................103
7.4. Tumor Response Assessments ..............................................................................104
7.5. Immunogenicity Evaluations.................................................................................105
7.5.1. Tremelimumab Immunogenicity Evaluations ..........................................105
7.5.2. PF-06801591 Immunogenicity Evaluations .............................................105
7.6. Banked Biospecimens ...........................................................................................106
7.6.1. Markers of Drug Response.......................................................................106
7.6.2. Additional Research..................................................................................107
7.7. Other Assessments ................................................................................................107
7.7.1. Tumor and Medical History......................................................................107
8. ADVERSE EVENT REPORTING....................................................................................107
8.1. Adverse Events......................................................................................................107
8.2. Reporting Period ...................................................................................................108
8.3. Definition of an Adverse Event.............................................................................108
8.4. Medication Errors..................................................................................................109
8.5. Abnormal Test Findings........................................................................................110
8.6. Serious Adverse Events.........................................................................................110
8.6.1. Protocol-Specified Serious Adverse Events.............................................111
8.6.2. Potential Cases of Drug-Induced Liver Injury..........................................111
8.7. Hospitalization ......................................................................................................112
8.8. Severity Assessment..............................................................................................114
8.9. Causality Assessment............................................................................................114
8.10. Exposure During Pregnancy................................................................................114
8.11. Occupational Exposure .......................................................................................116
8.12. Withdrawal Due to Adverse Events (See Also the Section on Patient 
Withdrawal).............................................................................................................116
CCI
CCI
CCI
CCI
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 52
8.13. Eliciting Adverse Event Information ..................................................................116
8.14. Reporting Requirements......................................................................................116
8.14.1. Serious Adverse Event Reporting Requirements ...................................116
8.14.2. Non-Serious Adverse Event Reporting Requirements ...........................117
8.14.3. Medical Device Complaint Reporting Requirements.............................117
8.14.4. Sponsor’s Reporting Requirements to Regulatory Authorities ..............117
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................118
9.1. Analysis Sets .........................................................................................................118
9.2. Statistical Methods and Properties ........................................................................119
9.2.1. Dose Escalation ........................................................................................120
9.3. Sample Size Determination...................................................................................120
9.4. Efficacy Analysis ..................................................................................................121
9.5. Safety Analysis......................................................................................................121
9.5.1. Analysis of Primary Endpoint ..................................................................122
9.5.2. Analysis of Secondary Safety Endpoints..................................................122
9.5.3. ECG ..........................................................................................................122
9.6. Analysis of Other Endpoints .................................................................................123
9.6.1. Pharmacokinetic Analyses........................................................................123
9.6.1.1. Tremelimumab Pharmacokinetics...........................................123
9.6.1.2. PF-06801591 Pharmacokinetics..............................................123
9.6.2. Immune Responses and Tremelimumab Immunogenicity .......................124
............................124
 
................................................................................................124
9.7. Data Safety Monitoring Committee ......................................................................125
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................125
11. DATA HANDLING AND RECORD KEEPING ...........................................................126
11.1. Case Report Forms/Electronic Data Record .......................................................126
11.2. Record Retention.................................................................................................126
12. ETHICS............................................................................................................................127
12.1. Institutional Review Board (IRB)/Ethics Committee (EC).................................127
12.2. Ethical Conduct of the Study ..............................................................................127
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 53
12.3. Patient Information and Consent.........................................................................127
12.4. Patient Recruitment.............................................................................................128
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................128
13. DEFINITION OF END OF TRIAL.................................................................................128
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................128
15. PUBLICATION OF STUDY RESULTS........................................................................129
15.1. Communication of Results by Pfizer ..................................................................129
15.2. Publications by Investigators ..............................................................................129
16. REFERENCES ................................................................................................................131
LIST OF TABLES
Table 1.
Adenovirus Available Dose Levels ..........................................................88
Table 2.
Dose Modifications for Adenovirus Related Toxicity..............................88
Table 3.
Tremelimumab Available Dose Levels ....................................................89
Table 4.
Dose Modifications for Tremelimumab Related Toxicity When 
Given in Combination with AdC68 or pDNA..........................................89
Table 5.
PF-06801591 Available Dose Levels .......................................................90
Table 6.
Dose Modifications for PF 06801591 and/or Tremelimumab (When 
Given in Combination With PF 06801591) Related Toxicity..................91
Table 7.
Probability of Escalating Dose ...............................................................119
Table 8.
Overall Response Derived from Changes in Index, Non-index and 
New Lesions ...........................................................................................146
LIST OF FIGURES
Figure 1.
Overall Study Design................................................................................71
Figure 2.
Cardiac Safety Monitoring Algorithm....................................................100
APPENDICES
Appendix 1. Abbreviations....................................................................................................136
Appendix 2. ECOG Performance Status................................................................................139
Appendix 3. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines.........................................................................................140

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 54
Appendix 4. Immune-Related Response Criteria Derived from RECIST 
1.1 (irRECIST) .......................................................................................145
Appendix 5. Guidelines for Evaluation of Bone Scans .........................................................148
Appendix 6. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) ......................................................................149
Appendix 7. Management of Immune-related Adverse Events (irAEs) including 
Myasthenia Gravis..................................................................................150

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 55
1. INTRODUCTION
1.1. Mechanism of Action/Indication
Vaccine-based immunotherapy regimen (VBIR) for prostate cancer (PrCa VBIR, 
PF-06753512) is an anti-cancer immunotherapy regimen that is currently being developed for 
the treatment of patients with various stages of prostate carcinoma.
1.2. Background and Rationale
Prostate cancer is the most common cancer in American men (aside from skin malignancies). 
The American Cancer Society’s estimates that in the United States in 2019 there will be 
174,650 newly diagnosed cases of prostate cancer and over 31,000 prostate cancer-related 
deaths.37 The early stages of prostate cancer are localized to the prostate, often indolent in 
nature, and treatable by operative resection or radiotherapy. However, the majority of 
patients are at a high risk of disease recurrence; and, once metastatic, of disease progression.  
Given this disease biology, there is a need for new therapies to provide long-term disease
control while offering a better quality of life with manageable side effect profiles.
Recent advances in understanding the mechanisms of immune surveillance and the reversal 
of immune tolerance have yielded encouraging therapeutic advances involving manipulation 
of the immune system to control specific tumor types.18,21,27,51 These approaches mostly 
encompass the use of single-agent therapies to enhance anti-tumor immune responses.  In 
contrast, the regimen used in this study, referred to as PF-06753512 or PrCa VBIR, is a 
combination approach using a vaccine combined with immune system modulators. Using 
this approach, T-cell derived, anti-prostate cancer immune responses are induced, expanded
and maintained long-term at the site of metastatic disease.
The study is divided in to two parts, Dose Escalation (Part A) followed by Dose Expansion 
(Part B).  Three clinical populations have been evaluated for safety in the Part A, Dose 
Escalation portion of the study for the PrCa VBIR:

Participants with metastatic castration resistant prostate cancer (mCRPC) who are 
either asymptomatic or minimally symptomatic with limited (non-visceral) metastatic 
disease before treatment with secondary hormonal manipulation (eg, abiraterone or 
enzalutamide).  Although these novel hormone therapies are approved for treatment 
of this population, many patients will experience progressive disease (median 
radiographic progression-free-survival [RPFS] of about 16 months for enzalutamide 
or abiraterone) and become symptomatic which requires chemotherapy (eg,
docetaxel).2,43

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 56

Participants with mCRPC for whom secondary hormonal manipulation has failed.  Up 
to 45% of patients develop resistance to novel hormone therapy within 6-9 months of 
treatment due to mutations in the androgen receptor (eg, AR-V7).1,11 In addition, for
approximately one third of these patients, a new phenotype emerges with highly 
aggressive small cell-like/undifferentiated neuroendocrine features.8 Patients 
resistant to novel hormone therapy such as abiraterone and/or enzalutamide have a 
very poor outcome due to the absence of therapeutic alternatives.  The PrCa VBIR 
may offer these patients a therapy that is anticipated to have few anti-androgen side 
effects; would delay disease progression; reduce the need for chemotherapy; and may
prolong survival.

Participants with hormone sensitive prostate cancer following definitive local therapy, 
who were determined to have rising prostate specific antigen (PSA) at a rate putting 
them at high risk for rapid development of metastatic disease (defined by a PSA 
doubling time <10 months).  Although there is no worldwide standard-of-care in this 
population, Androgen Deprivation Therapy (ADT) is frequently used when the PSA 
rises rapidly in the apparent disease-free setting (termed “Biochemical Relapse, or 
BCR”). The use of androgen deprivation impacts significantly the quality-of-life 
(QoL) of these patients. For example, sexual/hormonal dysfunction is a significant 
concern for many patients considering the duration of androgen deprivation,
(24 – 36 months), and its significant side effects of muscle wasting, fatigue, and 
reduction in libido. In this setting patients whose disease is BCR may benefit from a 
therapy with few androgen side effects, such as PrCa VBIR.  In patients with BCR, 
the goal will be to prevent or delay the need for chemical castration, preserve the QoL 
of the patients, and ultimately delay progression to metastatic disease.
Part B, the Dose Expansion phase of the study, will evaluate participants with metastatic 
castrate resistant prostate cancer (mCRPC) whose disease has progressed despite novel
hormonal treatment (enzalutamide or abiraterone) irrespective of the time of administration 
of these anti-androgen agents. Additionally, participants with biochemical relapse of disease 
(BCR), meaning there is no detectible metastatic disease, are included in Part B.
1.3. Overview of PrCa VBIR Regimen (PF-06753512)
An effective anti-tumor immune response should involve the activation of specific effector 
T cells and/or the production of functional anti-tumor antibodies targeted against antigens 
that are highly expressed by the patients’ tumor.  In this study, two antigen-delivery systems 
will be used in a heterologous prime/boost approach to elicit immune responses to several 
selected prostate cancer antigens.  As these are self-antigens, the antigen delivery systems 
were selected to break immune tolerance and to elicit high T cell titers.  The approach makes 
use of concomitant administration of immune modulators to drive immune response 
expansion as well as condition the immune suppressive tumor micro-environment to allow 
sustained immune-mediated killing of tumor cells.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 57
The initial PrCa VBIR regimen for prostate cancer (PF-06753512) consisted of three basic
components described below. A fourth component (described below) has now been added to 
the PrCa VBIR regimen, which is the anti-PD-1 antibody PF-06801591: 
1. A priming immunization with a replication-deficient adenovirus (AdC68) vector, 
derived from a chimpanzee-specific AdC68 that expresses three selected prostate 
cancer-specific antigens, administered intramuscularly (IM).
2. Plasmid deoxyribonucleic acid (DNA) booster vaccinations, encoding the same 
antigens, administered IM with an electroporation device (intramuscular TriGrid 
Delivery System (TDS-IM)).
3. Low dose anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) monoclonal 
antibody (tremelimumab) delivered subcutaneously (SC) in conjunction with each 
immunization at a site as close as possible to the vaccine vector delivery site.  The 
anti-CTLA4 administration is aimed at enhancing the vector-elicited immune 
response by blocking a natural mechanism for limiting antigen-specific T cell 
expansion.
4. In addition to the 3 agents described above, PF-06801591 will be added to treatment 
with PrCa VBIR.  PF-06801591 is a humanized, hinge region-stabilized 
IgG4 monoclonal antibody (mAb) specific for human PD-1. This antibody can 
selectively and reversibly bind to human PD-1 and block the interaction between
PD-1 and PD-L1/programmed death-ligand 2 (PD-L2). The administration of 
PF-06801591 will help maintain the PrCa VBIR-induced T cell response over time, 
by blocking the inhibitory effects against T-cells, which result from tumor-activated 
PD-1/programmed death-ligand 1 (PD-L1).
An overview of the rationale for the use of these three basic components of PrCa VBIR
described in more detail below:
1. The three prostate cancer specific antigens (Prostate-Specific Membrane Antigen 
[PSMA], Prostate-Specific Antigen [PSA], and Prostate Stem Cell Antigen [PSCA]) 
were selected on the basis of their over expression in prostate cancer tumors and 
metastatic lesions.7,13,14,23,29,35,49 The use of multiple tumor antigens within the 
prostate cancer vaccine will improve the probability that a greater percentage of 
patients will benefit from the vaccine, given that any single tumor antigen is not 
consistently expressed by every patient’s tumor lesion with different pathological 
grades and clinical stage. 
Adenovirus has been shown in nonclinical and clinical studies to activate high levels 
of cluster of differentiation (CD) 4 and CD8 T cell and B cell responses, which are 
essential effector mechanisms of the immune system5,50 (Study VR-VTR-10211).  
Since approximately 50% of patients in the US and Europe have pre-existing 
immunity to human adenovirus serotype 5,6,12,28 a chimpanzee adenovirus 
C68 (AdC68) with limited seroprevalence in humans was selected for the priming
vaccination. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 58
2. Due to T cell homeostasis, T cell responses contract a couple of weeks post induction 
and require boost vaccinations to ensure the immune pressure is maintained on the 
tumor.  Since humans develop neutralizing antibodies to adenovirus vectors, which 
prevent effective re-administration, the AdC68 priming vaccination will be followed 
by plasmid DNA boost vaccinations encoding PSMA, PSA, and PSCA administered 
IM with an electroporation device. 
3. Tremelimumab (anti-CTLA4) will be given locally by SC injection in conjunction 
with the priming and boost vaccinations.  This monoclonal antibody has been shown 
to increase responder frequency and enhance the breadth and magnitude of the T cell 
response to the selected cancer vaccine antigens. 
1.3.1. Rationale for the Components of PrCa VBIR
Evidence that high titers of tumor-specific T cells can eliminate large tumor burden has 
recently been demonstrated in patients with refractory chronic lymphocytic leukemia (CLL) 
treated with chimeric antigen receptor (CAR) T cells.36  In these clinical studies, peripheral 
blood mononuclear cells (PBMCs) are isolated from patients, modified ex vivo to express a 
tumor-antigen specific receptor and amplified before being adoptively transferred back into 
the patients.  Complete remission was achieved in 9/12 patients who had - before therapy - a 
tumor burden between 3-7 pounds, highlighting the anti-tumor potency of high avidity 
T cells.  The bolus injection of high numbers of high avidity T cells, however, resulted in
tumor lysis syndrome with high fevers, most likely triggered by the systemic release of high 
levels of interferon (IFN) by the activated T cells.  Unlike CARs, which are genetically 
modified T cells of high avidity, a cancer vaccine will induce polyclonal, tumor-antigen 
specific T cells.  Vaccine induced T cells are expected to be of lower avidity due to thymic
deletion of high avidity T cells specific for self-antigens.  Vaccine induced T cell responses 
are mounted after each vaccination and generally require multiple boost vaccinations before 
high T cell titers are reached.  The slower induction of T cells and thymic deletion of high 
avidity T cells might explain the good safety profile observed to date in patients treated with 
cancer vaccines. 
A therapeutic cancer vaccine has recently shown to provide some therapeutic benefit to 
patients with mCRPC in a randomized Phase 2 trial.19,22 The Prostvac vaccine consists of a 
Vaccinia virus prime vaccination followed by boost vaccinations using a fowlpox virus.  The 
viruses express the PSA and the three T cell costimulatory molecules LFA-3, B7.1 and 
ICAM-1.  Patients in the Prostvac arm had a median survival time of 25.1 months whereas 
patients in the control arm demonstrated a median survival time of 16.6 months which was 
statistically significant with a p-value of 0.0061.48 Therefore, Prostvac provides proof of 
concept that induction of T cell responses specific to PSA can provide some therapeutic 
benefit to patients with mCRPC.  PrCa VBIR may provide further therapeutic benefit to 
patients with prostate cancer for the following reasons: 
1. PrCa VBIR utilizes the adenovirus vector for prime vaccination which has been 
shown in non-human primates (NHPs) to be superior to the Vaccinia based modified 
vaccinia virus Ankara (MVA) vector at inducing high titers of antigen-specific 
CD8+ T cells.5

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 59
2. In preclinical models using PrCa VBIR, T cell responses are amplified at each prime 
and boost vaccination with the local delivery of anti-CTLA4 (tremelimumab) 
administered SC at close proximity to the vaccine draining lymph nodes.  Systemic 
delivery of an anti-CTLA4 monoclonal antibody in combination with cancer vaccines 
has recently been demonstrated to enhance the potency of two prostate cancer 
vaccines, namely Prostvac and GVAX30,53 In both non-randomized studies, the 
patients that received the cancer vaccine with anti-CTLA4 lived much longer than 
patients who received the cancer vaccine as monotherapy, as predicted by the Halabi 
nomogram,  a nomogram for predicting survival in men with CRPC.17 Using 
preclinical models, local delivery of anti-CTLA4 at close proximity of the vaccine 
draining lymph nodes was demonstrated to be superior at enhancing vaccine induced 
T cell responses when compared to systemic delivery of anti-CTLA4 in combination 
with a cancer vaccine.  These data suggest that local delivery of tremelimumab in the 
PrCa VBIR will activate higher tumor-antigen specific T cell titers than achieved 
when using systemic delivery of anti-CTLA4, in addition to eliminating the initial 
high systemic exposure to anti-CTLA4.
3. PrCa VBIR delivers, in addition to the PSA antigen, two more prostate specific 
antigens, namely PSCA and PSMA which are expressed in the majority of bone 
(PSCA) and lymph node (PSMA) metastatic lesions in prostate cancer patients.23,49
Most of the metastatic lesions in prostate cancer patients are indeed found in the bone 
and lymph nodes.
4. MDSCs have been found at high levels in prostate cancer patients54 and have been 
shown to blunt response to immunotherapy in metastatic melanoma patients treated 
with an anti-CTLA4 monoclonal antibody (ipilimumab, BMS).  In these studies it 
was demonstrated that patients with low levels of MDSCs at baseline responded 
better to anti-CTLA4 treatment than patients with higher pre-treatment MDSC 
levels.24
5. The PD-1/PD-L1 signaling pathway plays a critical role in mediating T-cell immune 
suppression in the local tumor environment.  Thus, anti-PD-1 monoclonal antibody 
(PF-06801591) when given with PrCa VBIR is anticipated to help induce high titers 
of tumor-specific T cells active long term at the tumor site.
Additional details of the pre-clinical studies can be found in the Investigator’s Brochure.
1.3.2. Safety and Part B Expansion Dose for PF-06753512 (PrCa VBIR) combined with 
PF-06801591 (anti PD-L1 antibody) 
As of 11 November 2019, 69 participants had been enrolled in the B7791001 study in 
Cohorts 1A and 2A (n=7), which include escalating doses of AdC68 (PF-06755992) ranging 
from 4 × 1011 VP to 6 × 1011 VP and a fixed dose of pDNA (PF-06755990) of 5 mg; Cohorts 
3A (n=6) and 1B (n=20), which include 6 × 1011 VP AdC68, 5 mg of pDNA, and 80 mg 
oftremelimumab; Cohort 6A (n=7) and 5B (n=12), which include 6 × 1011 VP AdC68, 5 mg 
of pDNA, 80 mg of tremelimumab, and 130 mg of PF-06801591; Cohort 9A (n=3), which 
includes 6 × 1011 VP AdC68, 5 mg of pDNA, 40 mg of tremelimumab and PF-06801591 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 60
130 mg; and Cohort 7A (n=14), which includes 6 × 1011 VP AdC68, 5 mg of pDNA, 80 mg 
of tremelimumab and PF-06801591 300 mg.
As of 11 November 2019, the most frequently experienced (≥5 participants) treatment related 
AEs were fatigue and influenza like illness (27 participants; 39.1% each), diarrhoea 
(14 participants; 20.3%), nausea and pyrexia (10 participants; 14.5% each), decreased 
appetite, and myalgia (9 participants; 13.0% each), injection site pain, alanine 
aminotransferase increased, headache, and amylase increased (8 participants; 11.6% each), 
aspartate aminotransferase increased, lipase increased, and arthralgia (7 participants; 
10.1% each), pruritus (6 participants; 8.7%), hyperthyroidism, hypothyroidism, abdominal 
pain, chills, vomiting, injection site discomfort, weight decreased, and hyponatraemia 
(5 participants; 7.2% each).
Adverse Drug Reactions (ADRs) identified for PrCa VBIR (PF-06753512) in combination 
with PF-06801591 include colitis and hypothyroidism.
Grade 4 myasthenia gravis and myositis as well as Grade 3 alanine aminotransferase and 
aspartate aminotransferase were reported in one participant dosed with PrCa VBIR in 
combination with PF-06801591. Myasthenia gravis and myositis have been reported with 
anti-PD-1, anti-PD-L1 and anti-CTLA-4 therapies. A blood sample was collected at 
screening for central evaluation of AChR antibodies and positive results were exclusionary.
Participants should be closely monitored for early detection of signs and symptoms of 
myasthenia gravis and/or myositits and should be instructed to contact the investigative site 
immediately should they experience diplopia, ptosis of the upper eyelid, difficulty to walk, 
talk or swallow, muscle weakness, or shortness of breath. 
Two participants on Study B7791001 experienced immune-mediated myocarditis.  Both
participants are in the earliest stage of prostate cancer recurrence and carried the diagnosis of 
“prostate cancer, biochemical relapse-only (“BCR”).  There have been no reports of 
immune-mediated myocarditis in participants with metastatic prostate cancer. 
One participant developed signs of myocardial inflammation (significant ECG changes) at 
22 days after the initiation of therapy, had elevated cardiac troponin consistent with 
myocardial injury, an endomyocardial biopsy showed lymphocytes infiltrating the 
myocardium, and responded to steroids and immunosuppressive therapy. The second 
participant presented with multi-system organ failure at 274 days from initiation of treatment. 
The participant presented with significant heart failure, along with markedly elevated cardiac 
troponin indicating myocardial injury. The participant died within 24 hours of 
hospitalization. No autopsy was performed to help determine the diagnosis. 
Based upon the above cases of immune-mediated myocarditis in Cohort 5B of Study
B7791001, participants will be screened prior to study entry for elevations in cardiac 
troponin (cTnI), a biomarker for cardiac inflammation or injury; if elevated, participants will 
be excluded from the study. In addition, serial cardiac monitoring of cTnI will be initiated 
for all on-going participants in B7791001 and dosing will not occur unless the cTnI is within 
normal limits.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 61
1.4. Nonclinical Safety
1.4.1. Nonclinical Toxicity Study for PrCa VBIR
The nonclinical safety of the AdC68, plasmid DNA (pDNA) and tremelimumab were 
assessed in a repeat-dose toxicity study in sexually-mature male monkeys.  The cynomolgus 
monkey was considered the appropriate species for the toxicity study because of the high 
homology (DNA/protein) of the three antigens between monkeys and humans, and because 
of the lack of activity of tremelimumab in rodents.  The safety of AdC68 was also evaluated 
following a single dose administered without tremelimumab, as part of the repeat-dose study 
in monkeys.  In a separate study, the tissue distribution and persistence of AdC68 was 
characterized using quantitative polymerase chain reaction (qPCR) following a single 
intramuscular injection in Cotton rats, a species that was demonstrated to express encoding 
antigens.
The repeat-dose toxicity study in monkeys used the same routes of administration and the
same dose regimen for the vaccine components and tremelimumab as proposed for this study.  
An initial priming dose of AdC68 was followed by 3 consecutive boost doses with pDNA 
followed by an additional boost with AdC68, all administered at 28-day intervals.  
Tremelimumab was administered by SC injection at a site local to the vaccine delivery site 
on the same days as vaccine administration.  The absolute dose of AdC68 (6x1011 VP) was 
the same as the highest proposed human dose.  The absolute dose of plasmid DNA (10 mg) 
was two times the proposed human dose.  Tremelimumab was evaluated at two dose levels 
(50 and 150 mg) when administered with the vaccine components, and at the 150 mg/dose 
level in the absence of the vaccine components, using the same monthly dosing regimen.  
In the repeat dose study, there was no evidence of systemic toxicity and findings were limited 
to the injection sites and the draining lymph nodes and are consistent with a local 
inflammatory reaction and generation of an immune response.  Mild non-adverse increases in 
monocytes, fibrinogen, thyroxine and marked increases in C-reactive protein consistent with 
an immune response associated with AdC68 administration were observed.  There were no 
indications of local irritation (erythema or edema) attributed to the administration of AdC68, 
tremelimumab or AdC68/pDNA/tremelimumab noted over the course of the dosing and 
recovery periods of the study.  Slight, transient increase in body temperature was noted 
24 hours after administration of the pDNA/tremelimumab in one animal; however, no 
consistent pattern was observed.
1.4.2. Nonclinical Toxicity Studies of PrCa VBIR with PF-06801591
The safety and toxicokinetics of the PrCa VBIR in combination with SC or intravenous (IV)
administered PF-06801591 was evaluated in a Good Laboratory Practice (GLP) study in 
sexually-mature male cynomolgus monkeys.  PF-06801591 was administered at a dose of 
20 mg/kg by SC or IV injection concurrently with the initial AdC68 prime dose and a single 
pDNA boost of the PrCa VBIR (2 injections, 1-month apart).  SC injections were made at a 
site local to the vaccine delivery site, adjacent to the tremelimumab injection site.  The safety 
of PF-06801591 administered by SC injection according to the same dose schedule in the 
absence of the PrCa VBIR was also evaluated as part of this study.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 62
There were no microscopic findings, changes in clinical pathology parameters, or other 
evidence of local or systemic toxicity when PF-06801591 was administered alone at 
20 mg/kg SC.  There was no evidence of systemic toxicity when the PrCa VBIR was 
administered in combination with SC or IV dosages of PF-06801591.  Mild, transient 
increases in globulin and moderate to marked increases in C-reactive protein (CRP) were 
observed following administration of the PrCa VBIR in combination with PF-06801591 on 
Days 1 and 28.  Transient increases in lymphocytes and/or monocytes, and fibrinogen were 
observed following administration on Day 1 only (priming dose with AdC68).  These 
changes were considered indicative of an inflammatory response to vaccine administration.  
Microscopic findings of minimal to mild chronic inflammation at the vaccine injection sites, 
and tremelimumab and PF-06801591 SC injection sites, were consistent with generation of 
an immune response against the vaccine components and localized effects at the injection 
sites.  All effects were considered nonadverse, because they were transient and/or based on 
the low magnitude and absence of correlating adverse clinical pathologic alterations.  
Increases in antigen-specific T cells were observed in all animals that received the vaccine 
components with tremelimumab and PF-06801591.  PF-06801591 exposures were similar on 
Days 1 and 29 when administered as a single agent by SC injection.  PF-06801591 exposures 
were lower on Day 29 compared to Day 1 when co-administered with the PrCa VBIR, 
possibly due to induction of anti-drug antibodies (ADA).  Tremelimumab exposures were 
similar when co-administered with SC or IV PF-06801591. 
Results of cytokine release assays conducted using tremelimumab and PF-06801591 in 
combination in human whole blood or PBMCs showed no synergistic effect on cytokine 
release when these agents were combined, and thus, indicate a low risk of human cytokine 
toxicity.
1.5. Pharmacokinetics of Tremelimumab and PF-06801591
1.5.1. Tremelimumab Pharmacokinetics After Intravenous Administration
The single-dose and multiple-dose pharmacokinetics (PK) of tremelimumab following 
intravenous (IV) administration have been studied in participants with varied tumor types, 
including solid tumors, melanoma, and prostate cancer (Studies A3671001, A3671002 and 
A3671004).  After IV administration, tremelimumab exhibited a biphasic disposition profile.  
Over the dose range of 0.1 to 15 mg/kg, mean values of the maximum drug concentration 
(Cmax) and the area under the concentration-time curve (AUC) increased with dose in an 
approximately proportional manner.  Tremelimumab had a low clearance (mean values 
ranged from 0.119 to 0.152 mL/hr/kg), a small volume of distribution (mean values ranged 
from 78.1 to 85.1 mL/kg), and a long terminal disposition half-life (t1/2; mean values ranged 
from 19.2 to 24.8 days).  After repeated administration at 10 mg/kg once every 4 weeks, the 
accumulation ratio based on AUC was approximately 1.26.
PK of tremelimumab after subcutaneous administration has not been evaluated in previous 
studies.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 63
1.5.2. PF-06801591 Pharmacokinetics
Single and multiple dose PK of PF-06801591 are being evaluated in the ongoing Phase 1b/2 
study B8011001 (Section 1.6.4.1). Preliminary PK data from Phase 1 cohorts suggest that 
PF-06801591 exhibits PK characteristics typical of IgG4 monoclonal antibodies.
The mean maximum serum concentration (Cmax) and area under the serum concentration-time 
curve over the dosing interval (AUCtau) of PF-06801591 increased in an approximately 
dose-proportional manner over the dose range of 0.5 -10 mg/kg following IV administration. 
The CV% values for Cmax and AUCtau were 24% to 35% and 22% to 36%, respectively
(n = 2-8 per dose level), following the first IV dose. After SC administration at 300 mg, 
PF-06801591 was slowly absorbed, with a median Tmax of approximately 8 days (n = 15). 
Steady state exposure after repeated SC dosing at 300 mg every 4 weeks fell within the range 
observed following IV dosing at 1 and 3 mg/kg, Q3W.
1.6. Starting Dose Rationale
Below are listed the rationales for the starting doses of the various components:
1.6.1. Clinical Adenovirus C68 Dosing
Anticipated efficacy and safety were considered when selecting the AdC68 dose range for 
clinical testing.  The dose ranges of 1 x 109 VP to 5 x 1011 VP of a modified adenovirus
antigen delivery system have shown a tolerable safety profile in patients with colorectal 
cancer as well as dose-dependent immune responses to a self-antigen.31 Previously, high 
doses of different adenovirus vectors were evaluated preclinically.  The absence of germ line 
transmission was demonstrated in mice and baboons.38,56 In a separate study in NHPs, a dose 
of 5 x 1012 VP/kg was found to be well tolerated.39 Importantly, repeated administration did 
not appear to alter the toxicity/tolerability profile.34 It is also important to note that these 
animals were dosed IV per kg body weight, making the total dose substantially higher than 
the highest dose planned in this study (6 x 1011 VP IM total dose).  Furthermore, since the 
administration in this study is IM, the systemic safety profile is anticipated to be more 
favorable.38 Higher doses of adenovirus, up to 2 x 1011 VP/kg (total dose in excess of 1 x 
1013 VP), when administered directly into the hepatic artery are tolerated in patients with 
partial ornithine transcarbamylase deficiency.40
In the toxicity study of AdC68, plasmid DNA and tremelimumab in monkeys, the safety and 
antigen-specific T-cell responses were evaluated following administration of AdC68 at 
6 x 1011 VP, either as a single agent or in combination with plasmid DNA and tremelimumab 
using the same dosing frequency as planned for the Phase 1 study.  As described in 
Nonclinical Safety, there was no evidence of systemic toxicity in the study and findings were 
limited to the injection sites and the draining lymph nodes. 
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 64
Based on the above safety and immune response data, a starting dose of 4 x 1011 VP
administered IM has been selected as the starting dose for AdC68 in this study.
1.6.2. Clinical Plasmid DNA Dosing
Efficacy and safety were factors considered to select the DNA dose for clinical testing.  DNA 
doses of 0.2 to 8 mg have been reportedly delivered in clinical trials by other sponsors using 
the Ichor TDS electroporation device.  In NHPs, the data collected to date demonstrated that 
electroporation of DNA dose at 5 mg can effectively and reproducibly boost AdC68 vector 
primed IFNCD8 T cell responses to a self-antigen in the presence of tremelimumab.  A 
DNA dose of 10 mg was well tolerated but no significant benefit on the magnitude or 
responder frequency of the IFNCD8 T cell responses was observed. Thus, a dose of 5 mg 
is selected for the DNA for clinical testing.
1.6.3. Clinical Tremelimumab Dosing
More than 1000 participants with cancer have been treated with tremelimumab as 
single-agent or in combination with another anti-cancer treatment.  Clinical safety data for 
tremelimumab, at IV doses ranging from 0.01 to 15 mg/kg, indicate an acceptable safety 
profile in participants with cancer.  The established maximum tolerated dose (MTD) for 
single-agent therapy is 15 mg/kg IV every 12 weeks, a dose level that has been extensively 
studied in a Phase 3 trial in participants with melanoma.41 Diarrhea, pruritus, and rash were 
the most common treatment-related adverse events (AEs) associated with tremelimumab.  
Another important event observed related to tremelimumab was hypopituitarism.
Monthly dosing, as planned for this study, was tested in the clinic in participants with 
melanoma, where administration of up to 10 mg/kg IV monthly3 was tolerated with no 
dose-limiting toxicity observed. The overall profile was found to be acceptable with the 
most frequent treatment-related AEs being diarrhea, rash, and pruritus.  Frequency of 
Grade 3/4 AEs was 27% in the participants dosed with 10 mg/kg once every month.
The highest dose of tremelimumab will not exceed 150 mg, which equals to 2 mg/kg for a 
75 kg patient, is expected to lead to a systemic exposure not exceeding that of a 2 mg/kg 
IV dose in a 75 kg patient.  Thus, the AUC and Cmax of this dose are expected to be lower 
than those of the 10 mg/kg dose of tremelimumab previously administered to participants 
monthly via the IV route as described above. 
Given the lower doses and the different route of administration, SC rather than 
IV administration, this study will start at a dose level of 80 mg total dose SC.  In the event 
that 80 mg SC is not tolerated, lower dose levels (eg, 40 mg) may be tested.
1.6.4. Clinical PF-06801591 Dosing
The starting dose of PF-06801591 will be at 130 mg, administered SC every 4 weeks (Q4W)
in combination with the PrCa VBIR.  Upon evaluation of the emerging safety (including late 
onset toxicities) and PK data of PF-06801591 from the initial PF-06801591 dosing cohort in
all participants for 4 weeks or longer, a higher PF-06801591 dose of 300 mg was selected for 
further evaluation with escalating doses of tremelimumab.  The specific dose level for 
PF-06801591 dosing cohorts was selected to achieve the systemic exposure that has shown to 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 65
be therapeutically effective for similar anti-PD-1 mAbs, not to exceed 300 mg due to the 
limitation of injection volume.  The starting dose of 130 mg was selected based on data from 
nonclinical safety studies of PrCa VBIR in combination with PF-06801591, and known 
dose/exposure-response relationships of similar anti-PD-1 monoclonal antibodies.  The 
steady-state Cmax and AUC0-tau, following SC administration of PF-06801591 at 130 mg 
Q4W in humans, were predicted to be approximately 8% and 43%, respectively, of the Cmax
and AUC of the no observed adverse effect level (NOAEL) determined from the nonclinical 
safety study of the PrCa VBIR in combination with PF-06801591 in cynomolgus monkeys.  
Also, the predicted steady state Cmax and average concentration (Caverage) of PF-06801591 at 
130 mg Q4W are comparable or lower than those achieved by nivolumab or pembrolizumab 
at tolerated intravenous dose levels, either given alone or in combination with an 
anti-CTLA4 mAb (Keytruda [pembrolizumab] United States Package Insert (USPI) version 
12/2015; Opdivo [nivolumab] USPI version 3/2015).
1.6.4.1. PF-06801591, an Anti-PD-1 Antibody: Clinical Experience in Study B8011001 
(NCT02573259)
B8011001 is an ongoing Phase 1, open-label, multi-center, multiple-dose, dose escalation 
and expansion, safety, PK, and PD study of PF-06801591.  The primary purpose of this study 
is to evaluate safety and early signs of efficacy.  This clinical study was divided into a dose 
escalation (Part A) phase and a dose expansion (Part B) phase.  One hundred forty-six 
participants have been dosed on the study.  No dose limiting toxicity was observed and there
was no maximum tolerated dose identified.
Part A Dose Escalation
Part A dose escalation evaluated 4 pre-specified IV dose levels (0.5, 1, 3, and 10 mg/kg 
administered every 3 weeks [Q3W]), and 1 subcutaneous (SC) dose level (300 mg 
administered every 4 weeks [Q4W]) in adult participants with locally advanced or metastatic 
melanoma, squamous cell cancer of head and neck, ovarian cancer, sarcoma, small cell lung 
cancer, adenocarcinoma of salivary gland, endometrial adenocarcinoma, malignant peritoneal 
neoplasm, esophageal adenocarcinoma or renal cell carcinoma.  Participants had progressive 
disease on ≥1 prior line of therapy for locally advanced or metastatic disease or refused 
standard of care therapy; were not previously treated with an anti-PD-1/PD-L1 agent; and 
had adequate renal, bone marrow, liver, and cardiac function, with Eastern Cooperative 
Oncology Group (ECOG) performance status 0 or 1.  Forty participants were enrolled into 
Part A with 25 participants total enrolled into the IV dose cohorts and 15 participants 
enrolled into the SC dose cohort.  
Part B Dose Expansion
The 300 mg SC dose was evaluated in an expanded population of 106 participants.  This 
included 68 participants with locally advanced or metastatic non-small cell lung cancer 
(NSCLC) and 38 participants with locally advanced or metastatic urothelial carcinoma who 
were anti-PD-1 or anti-PD-L1 treatment-naïve and who had progressive disease on or were 
intolerant to systemic therapy or for whom standard of care systemic therapy was refused or
unavailable.  Participants with NSCLC could have received up to 1 line of prior systemic 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 66
therapy for locally advanced or metastatic disease and if they had known epidermal growth 
factor receptor (EGFR) activating mutation or an anaplastic lymphoma kinase (ALK) 
rearrangement were required to have, in addition, at least 1 targeted therapy for their disease.  
Participants with UC could have received up to 2 lines of prior systemic therapies for locally 
advanced or metastatic disease.  The selected participants had adequate renal, bone marrow, 
liver, and cardiac function, with ECOG performance status 0 or 1.  All participants received 
300 mg of PF-06801591 SC every 4 weeks. 
Complete information for PrCa VBIR may be found in the single reference safety documents 
(SRSD). The SRSDs for this study are the PF-06753512 Investigator’s Brochure for: AdC68 
(PF-06755992), plasmid DNA (PF-06755990), PF-06801591, and tremelimumab. 
The SRSD for the electroporation device is the TrigridDelivery System electroporation
device Investigator’s Brochure. 
Additional reference information can be found in the individual tremelimumab IB and the 
PF-06801591 IB.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Part A Objectives
Part A Primary Objective

To assess safety and tolerability of increasing dose levels of the prostate cancer 
vaccine-based immunotherapy regimen (PrCa VBIR) components alone and in 
combination with increasing doses of PF-06801591.

To characterize the dose limiting toxicities (DLTs), if any are observed, and overall 
safety profile of escalated doses of the PrCa VBIR components alone and in 
combination with increasing doses of PF-06801591.

To determine the Part B Expansion Dose for the PrCa VBIR components and 
PF-06801591in combination.
Part A Secondary Objectives

To evaluate the immune response elicited by the PrCa VBIR to the selected prostate 
cancer tumor-antigens.

To evaluate the overall safety profile in prostate cancer participants.

To evaluate the PK of tremelimumab after SC administration.

To evaluate the PK of PF-06801591 after SC administration.

To evaluate the anti-drug antibody (ADA) response of tremelimumab after SC 
administration with the other PrCa VBIR components.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 67
•
To evaluate the ADA response of PF-06801591 after SC administration with the other 
PrCa VBIR components.
Part A Exploratory Objectives
•
To document any preliminary evidence of anti-tumor activity.
 
 
2.2. Part A Endpoints
Part A Primary Endpoint
•
Incidence and grade of treatment-emergent adverse events including DLTs as graded 
by National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI CTCAE version 4.03). 
Part A Secondary Endpoints
•
Immune response including T cells specific to the three selected prostate cancer 
tumor-antigens.
•
Laboratory abnormalities as characterized by type, frequency, severity (as graded by 
NCI CTCAE v 4.03) and timing.
•
Tremelimumab single-dose PK parameters, including the maximum concentration 
(Cmax), time to maximum concentration (Tmax), and area under the concentration 
versus time curve (AUC) from time zero to the last quantifiable time point prior to the 
second tremelimumab dose (AUClast) and if data permit, AUC from time zero 
extrapolated to infinity (AUCinf); and trough concentrations after multiple dosing
(Ctrough).
•
PF-06801591 single-dose PK parameters, including Cmax, Tmax, AUClast, and if data 
permit, AUCinf; and Ctrough after multiple dosing.
•
Incidence and titers of ADA and neutralizing antibodies against tremelimumab.
•
Incidence and titers of ADA and neutralizing antibodies against PF-06801591.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 68
Part A Exploratory Endpoints
•
Objective tumor response, as assessed using the Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 (Appendix 3) by calculating the Objective Response 
Rate (ORR) and Progression-Free Survival (PFS).
•
Antitumor response and tumor control duration based on total measurable tumor 
burden as assessed by the Immune-Related Response Criteria Derived from 
RECIST 1.1 (irRECIST) (Appendix 4).
•
Bone outcome according to Prostate Cancer Working Group 3 (PCWG3) criteria.44
(Appendix 5)
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 69
2.3. Part B Objectives and Endpoints
Primary Objective(s): 
Primary Endpoint(s): 
•
To evaluate the overall safety profile of the 
PrCa VBIR + PF-06801591 in prostate cancer 
participants.
•
Incidence and grade of treatment-emergent 
adverse events including DLTs as graded by 
National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE 
version 4.03).
•
Laboratory abnormalities as characterized by 
type, frequency, severity (as graded by NCI 
CTCAE v 4.03) and timing.
Secondary Objective(s): 
Secondary Endpoint(s): 
•
For Cohort 3B: To evaluate the anti-tumor response 
induced by treatment in participants with mCRPC 
utilizing solid tumor response criteria.
•
For Cohort 3B: To evaluate the anti-tumor response 
induced by treatment utilizing immune related 
response criteria.
•
For Cohort 3B: to evaluate bone metastatic disease 
outcome in participants with mCRPC.
•
For Cohorts 3B: To estimate the duration of 
radiographic Progression-Free Survival (rPFS) in 
participants with mCRPC.
•
To evaluate response rate based on 50% reduction of 
prostate specific antigen (PSA).
•
To evaluate PSA kinetics.
•
To evaluate trough concentrations of tremelimumab
after SC administration at selected doses.
•
To evaluate trough concentrations of 
PF-06801591 after SC administration at selected 
doses. 
•
To evaluate the anti-drug antibody (ADA) response 
of tremelimumab after SC administration with the 
other PrCa VBIR components.
•
To evaluate the ADA response of PF-06801591 after
SC administration with the other PrCa VBIR 
components.
•
For Cohort 3B: Objective response rate (ORR) and 
duration of response, as assessed using the Response 
Evaluation Criteria in Solid Tumors (RECIST) 
version 1.1 (Appendix 3). 
•
For Cohort 3B: Antitumor response and tumor control 
duration based on total measurable tumor burden as 
assessed by the Immune-Related Response Criteria
Derived from RECIST 1.1 (irRECIST) (Appendix 4).
•
For Cohort 3B: Bone outcome according to Prostate 
Cancer Working Group 3 (PCWG3) criteria
(Appendix 5).44
•
For Cohort 3B: Radiographic Progression-Free 
Survival (rPFS) by RECIST 1.1, irRECIST and 
PCWG3 Criteria in participants with mCRPC.
•
PSA-50 response rate and duration of response.
•
Baseline and changes from baseline for PSA, PSA 
velocity, PSA slope and PSA doubling time (PSADT).
•
Trough concentrations after multiple dosing (Ctrough).
•
Ctrough after multiple dosing.
•
Incidence and titers of ADA and neutralizing 
antibodies against tremelimumab.
•
Incidence and titers of ADA and neutralizing 
antibodies against PF-06801591.
 
 
 
 
 
 
 
 
 
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 70
 
 
 
 
3. STUDY DESIGN
3.1. Study Overview
This is a Phase 1, open label, multi-center, multiple dose, safety, PK, 
 and 
immunogenicity study evaluating the components of a vaccine-based immunotherapy 
regimen for prostate cancer (PrCa VBIR). PrCa VBIR consists of the following components: 
Adenovirus (AdC68), pDNA and tremelimumab.  In addition, cohorts will evaluate PrCa 
VBIR when given in combination with PF-06801591.
The study is divided in to two parts, Dose Escalation (Part A) followed by Dose Expansion
(Part B).  The overall design is presented in Figure 1 below. 
Participants will participate in the treatment period of the study for approximately 9 months.  
This includes a 28 day screening period followed by two cycles of treatment (each 4 months 
in duration for a total of 8 months).  Participants will then enter the maintenance phase of the 
study where they will continue to receive their assigned components, at the frequencies 
outlined in the schedule of activities.  Treatment will continue until: disease progression, 
participant refusal or unacceptable toxicity occurs.  Participants who demonstrate clinical 
benefit with manageable toxicity and who are willing to continue receiving study treatment 
will be given the opportunity to continue treatment upon agreement between the investigator 
and sponsor.  When the participant discontinues treatment, they will then enter a 6 month 
post-dose follow-up period.  The end of the study is the last participant last visit.
A cycle of the PrCa VBIR includes at minimum an AdC68 priming dose given 
intramuscularly (IM) on Day 1, followed by a total of three doses of DNA, given IM using an 
electroporation device at 4-week intervals for another 12 weeks (16 weeks total).  Beginning 
with Cohort 3A, the PrCa VBIR cycle will also include tremelimumab given as SC injections 
at close proximity to the vaccinated muscles and the vaccine draining lymph nodes every 
four weeks at the immunization time points.  For participants enrolled in Cohorts 6A through 
9A or Cohorts  3B or 5B, the PrCa VBIR cycle will also include PF-06801591 given as SC
injections at close proximity to the vaccinated muscles and the vaccine draining lymph nodes 
every four weeks at the immunization time points.  After completing two cycles of treatment
(≈8 months treatment duration), the participants will then enter the maintenance phase of the 
study.
CCI
CCI
C

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 71
Figure 1.
Overall Study Design
The dose of each component evaluated in subsequent cohorts was determined based on the 
safety data from previous cohorts.  
The treatment effect of cancer immunotherapy can often be delayed.  Therefore, participants 
should be encouraged to continue on study treatment for at least 24 weeks before an 
investigator considers removing the participant due to disease progression, as long as:

Participant and investigator agree.

Participant continues to meet all other study protocol eligibility criteria.

Acceptable toxicity.

No deterioration of participant performance status.
If a participant withdraws from the study before Day 29 for reasons other than investigational 
product-related toxicity, another participant may be enrolled to replace that participant at the 
current dose level.  In principle, all participants must be evaluated for 28 days following the 
first AdC68 vaccination.  However, if a participant discontinues close to Day 29 for reasons 
other than toxicity, but due to a clear drug unrelated event (eg, traffic accident, clear disease 
progression), the participant may be deemed evaluable for safety if the investigator and 
sponsor’s medical monitor both agree that the participant is suitable for inclusion in the dose 
limiting toxicity (DLT) evaluation group.
3.1.1. Dose Escalation (Part A)
The principles of 3+3 design were utilized for the dose escalation portion of the study.  The 
dose escalation could include an increase in the dose of one component of the regimen or 
could include the addition of the lowest dose of an additional component.  Dose escalation 
followed the scheme presented in Figure 1, assuming dose levels were achieved with 0 out of 
the initial 3 or maximum 1 out of the initial 6 participants developing DLTs.  For each 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 72
component the highest tested dose level was used for subsequent cohorts unless the highest 
dose level is not tolerated (>1 out of the initial 3 to 6 participants developing DLT).  If DLT 
occurred in >1 out of the initial 3 to 6 participants at the higher dose level then the lower 
level will be administered to subsequent cohorts. Intrapatient dose escalation was not 
permitted.
Activation of each cohort occurred no sooner than 28 days after the first three participants (or 
6 participants if a DLT is observed and the cohort is expanded) receive the first 
AdC68 vaccination, but may occur later if the sponsor and investigators determine additional 
safety data is needed.  The Pfizer clinical team and investigators reviewed all available safety 
data from the previous and current cohorts prior to making a decision to dose escalate. If no 
safety issues that would prohibit dose escalating were observed, the next cohort of 
participants would be open for accrual.
Part A dose escalation started with the lowest dose of AdC68, followed by three plasmid 
DNA boosts (5 mg fixed dose) in 4 week intervals (Cycle 1), repeated for two cycles. Since 
no identified unacceptable toxicity was reported in the first 2 cohorts (1A and 2A), the 
AdC68 dose of 6 x 1011 VP was used for all subsequent cohorts.  In Cohort 3A,
tremelimumab was added at 80 mg. Starting with Cohort 6A, the dose escalation of 
PF-06801591 in combination with PrCa VBIR started with a low dose (130 mg) and was 
then escalated up to 300 mg.  
Based on the emerging safety and PK data from Cohort 3A, enrollment of participants in 
Expansion Cohort 1B was initiated allowing for adequate evaluation of the safety of PrCa 
VBIR with tremelimumab 80 mg. Likewise, enrollment of participants in Expansion Cohort 
5B was initiated allowing for adequate evaluation of the safety of PrCa VBIR in combination 
with 130 mg of PF-06801591 based on the safety data from Cohort 6A.
Based on safety data from Cohort 7A, the Part B Expansion Dose for participants with 
mCRPC whose disease progressed after novel hormone therapy was determined to be AdC68 
6 x 1011 VP + plasmid DNA 5 mg + tremelimumab 80 mg + PF-06801591 300 mg.  
Enrollment in Expansion Cohort 3B was initiated at the Part B Expansion Dose, in order to 
further assess the safety, immune response, pharmacokinetics, and pharmacodynamics of 
PrCa VBIR of this dose level in the mCRPC population.
3.1.2. Dose Expansion (Part B)
In Part B, the selected doses of the PrCa VBIR in combinations with PF-06801591 were
evaluated in two populations: (1) Participants with mCRPC whose disease has progressed 
despite novel hormone therapy (abiraterone or enzalutamide) to be treated with PrCa 
VBIR+ PF-06801591 alone; and (2) Participants with biochemical relapse of disease (BCR)
to be treated with PrCa VBIR+ PF-06801591.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 73
The study design has changed in two aspects: (1) in the removal of Cohort 10B, because 
studies of progression on novel-hormone therapy with abiraterone, with a switch to 
enzalutamide + Pr Ca VBIR, are no longer useful in defining Proof of Concept for this study; 
and (2) in no longer expanding cohort 3B, because sufficient sample size has been reached to 
make decisions about further development based upon safety and preliminary efficcacy. 
The following listing identifies the Expansion Cohorts for Part B:  

Cohort 1B (20 participants treated): Twenty participants with BCR have been 
enrolled and treated in this expansion cohort, using PrCa VBIR and tremelimumab at 
a dose level of 80 mg.  No PF-06801591 was included in this regimen. No 
additional participants will be enrolled.

Cohort 5B (15 participants treated): Fifteen participants with BCR and no prior
therapy have been treated with PrCa VBIR in combination with 130 mg
PF-06801591. No additional participants will be enrolled.

Cohort 3B (18 participants treated):  Eighteen participants with mCRPC whose
disease has progressed despite novel hormonal treatment (enzalutamide or
abiraterone) have been treated with PrCaVBIR in combination with 300 mg 
PF-06801591. No additional participants will be enrolled.
Different cohorts of patients opened for enrollment in parallel. Cohorts are non-randomized; 
slot assignments were managed by the study team with sites notified in advance of cohort 
availability.  Participants are not allowed to crossover between the different combinations 
evaluated in this study.
3.1.3. Maintenance Treatment Period
To mimic the immune response induced by the PrCa VBIR encoding tumor associated 
self-antigens in non-human primates, the response induced by the PrCa VBIR encoding a 
rhesus PSMA (rhPSMA) antigen was evaluated.  Durable and high magnitude induction of 
polyfunctional IFNCD8 and CD4 T-cell titers recognizing rhPSMA were observed by 
2 cycles of the PrCa VBIR with a 100% responder frequency.  The immune response was 
maintained long term (3-4 month) after discontinuation of vaccination post completion of the 
second PrCa VBIR cycle.  The IFNCD8 titers recognizing rhPSMA with cytolytic ability 
declined slightly approximately 2 months after discontinuation of vaccination.  At Week 57, 
26 weeks after the last of 8 vaccinations, re-administration of pDNA given concurrently with 
tremelimumab rapidly increased the magnitude of self-antigen specific polyfunctional and 
cytolytic T-cell responses. Based on these data, following 2 cycles of the PrCa VBIR, a 
maintenance boost cycle of 2 months with DNA delivered by electroporation and SC
injections of tremelimumab is proposed as long as the participant derives clinical benefit.  
Participants will also continue to receive monthly PF-06801591 as received prior to the 
maintenance treatment period, where applicable.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 74
3.2. DLT Definition
Severity of adverse events will be graded according to CTCAE version 4.03.  For the purpose 
of dose escalation, any of the following adverse events occurring in the first 28 days 
following the first AdC68 vaccination that are not considered related to disease/progression 
will be classified as DLTs:
Hematologic:
The following DLT criteria apply to participants enrolled in Cohorts 1A through 4A and 
Cohorts 6A through 9A only:

Grade 3 neutropenia lasting >7 days.

Febrile neutropenia (febrile neutropenia is defined as an absolute neutrophil count 
<1.0 × 109/L with a single temperature of >38.3C, or 101F, or a sustained 
temperature of 38C, or 100.4F, for more than one hour).

Grade 3 neutropenic infection.

Grade 3 thrombocytopenia.

Grade 3 anemia lasting more than 7 days.

Grade 3 lymphopenia lasting more than 14 days.
Non-hematologic:
The following criteria apply to all cohorts:
Non-hematologic laboratory abnormalities:

Grade 3 laboratory abnormalities either associated with symptoms or associated 
with worsening of an existing condition or that suggests a new disease process or that 
requires additional active management (eg, discontinuation of the drug, close 
observation, more frequent follow-up assessments, further diagnostic investigation or 
specific treatment).

The following will not be considered DLTs: elevation of 
gamma-glutamyltransferase (GGT), elevation of alkaline phosphatase, 
hypo/hyperchloremia, hypo/hyperphosphoremia, hypoalbuminemia, 
hypomagnesemia, hypocalcemia of less than 15 days, amylase or lipase elevation 
not associated with clinical symptoms that spontaneously resolved within 7 days 
to Grade 1 or baseline, and Grade 3 aspartate aminotransferase (AST) or 
alanine aminotransferase (ALT) that spontaneously resolve within 7 days to 
Grade 1 or baseline.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 75
Other non-hematologic events:

Grade 3 toxicities, including toxicities of the major organs which include heart, 
kidney, liver, lung, colon, pancreas, brain and adrenal, hypophysis and thyroid glands. 

Those toxicities that have been adequately treated (eg, nausea, vomiting, diarrhea) are 
not considered DLTs.

Grade 3 flu like symptoms lasting greater than 3 days with adequate treatment.

Fever of >40.0C, or 104.0F, lasting for more than 3 days with adequate treatment.
In addition, clinically important or persistent toxicities that are not included in the above 
criteria may be considered a DLT following review by Pfizer and the investigators.
3.3. MTD Definition for Part A
An MTD may not be identified, as DLTs are not frequently observed with cancer vaccines.  
However, since PrCa VBIR includes non-vaccine components, the potential for DLTs has to 
be taken into account.  In practice, according to the 3+3 design, the MTD estimate, for each 
component being escalated, is the dose level at which 0/3 or 1/6 evaluable participants
experience a DLT within 28 days after the first AdC68 vaccination with the next higher dose 
having at least 2 of the initial 3 to 6 participants experiencing DLTs.
Adverse events occurring in Part B that meet the same grading criteria as the DLT criteria in 
Part A will be discussed with the Principal Investigators. During this discussion, a review of 
the details of the toxic effects and their clinical impact will be undertaken. Following this 
discussion with the Principal Investigators, a decision will be made by the Sponsor as to 
whether any action needs to be taken related to changing the dosing in any specific cohort of 
participants.
3.4. Part B Expansion Dose
The Part B Expansion Dose for each component is the dose chosen for further study based on 
Phase 1 study results.  
3.4.1. Part B Expansion Dose: Participants with mCRPC (Cohort 3B) 
1. AdC68: 6x1011 VP administered IM.
2. pDNA: 5 mg administered IM with electroporation device.
3. Tremelimumab: 80 mg administered SC:
3a. Tremelimumab dose may be decreased to 40 mg SC depending upon 
emerging safety data.
4. PF-06801591: 300 mg administered SC:

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 76
4a. PF-06801591 dose may be decreased to 130 mg SC depending upon emerging 
safety data.
3.4.2. Part B Expansion Dose: Participants with Rising PSA at High Risk for 
Recurrence After Definitive Local Therapy (Biochemical Relapse or BCR)
1. AdC68: 6x1011 VP administered IM.
2. pDNA: 5 mg administered IM with electroporation device.
3. Tremelimumab: 80 mg administered SC:
3a. Tremelimumab dose may be decreased to 40 mg SC depending upon 
emerging safety data.
4. PF-06801591: 130 mg administered SC:
Dosing for tremelimumab and PF-06801591 will be explored as follows: Dosing may start 
with tremelimumab at 80 mg + PF-06801591 130 mg in an initial group of 3 to 6 patients. A 
decision will be made whether to continue tremelimumab at 80 mg with an increase of 
PF-06801591 to 300 mg, if the starting dose level is tolerated; or to decrease tremelimumab 
to 40 mg keeping PF-06801591 at 130 mg or increasing PF-06801591 to 300 mg based upon 
emerging safety data. The final dose level for this population will then be selected to 
complete this cohort.
3.5. Declaration of RP2D
At the conclusion of the Part B, Dose Expansion, a RP2D will be declared for the mCRPC 
and BCR cohorts. The RP2D declaration will be based upon the totality of the clinical 
evidence, including safety, efficacy, PK/PD, and any other information relevant to this 
decision.
4. PARTICIPANT SELECTION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and non-medical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this
protocol.
4.1. Inclusion Criteria for All Participants
Participant eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before participants are included in the study. 
Participants must meet all of the following inclusion criteria to be eligible for enrollment into 
the study:
1. Histological or cytological diagnosis of adenocarcinoma of the prostate.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 77
2. Men age 18 years.
3. Adequate Bone Marrow Function, including:
a.
Absolute Neutrophil Count (ANC) 1,500/mm3 or 1.5 x 109/L;
b. Platelets 100,000/mm3 or 100 x 109/L;
c.
Hemoglobin 9 g/dL.
4. Adequate Renal Function, including:
a.
Serum creatinine 1.5 x upper limit of normal (ULN) or estimated creatinine 
clearance 60 ml/min as calculated using the method standard for the institution. 
5. Adequate Liver Function, including:
a.
Total serum bilirubin 1.5 x ULN unless the participant has documented Gilbert 
syndrome;
b. Aspartate aminotransferase and Alanine aminotransferase (AST and ALT) 
2.5 x ULN; 5.0 x ULN if there is liver involvement secondary to tumor; 
c.
Alkaline phosphatase 2.5 x ULN; (5 x ULN in case of bone metastasis). 
6. Resolved acute effects of any prior therapy to baseline severity or CTCAE 
Grade 1 except for AEs not constituting a safety risk by investigator judgement.  
Post-surgical pain will not be considered a basis for exclusion.
7. Evidence of a personally signed and dated informed consent document indicating that 
the participant has been informed of all pertinent aspects of the study.
8. Participants who are willing and able to comply with scheduled visits, treatment 
plans, laboratory tests and other procedures.
4.1.1. Additional Inclusion Criteria for Participants with Rising PSA at High Risk for 
Recurrence After Definitive Local Therapy (Biochemical Relapse)
9. Definitive loco-regional therapy for primary diagnosis including one of the following:
a.
External radiotherapy or any salvage therapy including but not limited to 
brachytherapy, cryotherapy or salvage therapy;
b. Radical prostatectomy and radiotherapy therapy, such as external radiotherapy or 
brachytherapy;

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 78
c.
Prostatectomy only for participants who are not candidates for salvage therapy. 
Salvage therapy includes but is not limited to any of the following: any radiation 
therapy (such as external beam therapy, brachytherapy) or any other salvage 
therapy such as cryotherapy.
10. Hormone sensitive (androgen dependent) relapsing prostate cancer post definitive 
local therapy.  Relapse is defined as a subsequent detectable PSA (≥0.2 ng/ml) that 
increases on 2 or more determinations after radical prostectomy. The values must be
separated by at least 2 weeks.  
11. High risk of development of metastatic disease defined as PSA doubling time less 
than or equal to 10 months (calculated at least 3 months before treatment 
administration).  The PSADT calculation must include all available PSA values 
available over the past 6 months prior to registration using the Memorial Sloan 
Kettering Cancer Center (MSKCC) PSA Doubling Time Prediction Tool available at 
the following website: http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx.
12. Male participants able to father children must agree to use one highly effective 
method of contraception throughout the study and for at least 90 days after the last 
dose of assigned treatment. 
13. No concurrent use of ADT or orchiectomy. Prior use of ADT in the neoadjuvant or 
adjuvant setting with radiotherapy is allowed as long as it was completed at least 6 
months prior to registration.
14. No evidence by imaging (of any type) of metastatic involvement as follows:
loco-regional or distant lymph nodes; loco-regional or distant soft tissues; or any
organ involvement, including bone.
15. Testosterone level ≥150 ng/dL.
4.1.2. Additional Inclusion Criteria for Participants in Part B Expansion 
Cohort 3B - After Novel Hormone Treatment (enzalutamide or abiraterone) 
16. Prior therapy with a novel hormone therapy (enzalutamide or abiraterone) . 
17. Testosterone levels <50 ng/dL. 
18. Documented progressive disease and/or local recurrence defined by the following 
modified PCWG344 criteria:
a.
PSA progression defined as a minimum of 2 consecutive rising levels, with an 
interval of 1 week between each determination.  For Part B only, the last 
determination must have a minimal value of 0.2 ng/mL and be determined 
within two weeks prior to screening.
OR

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 79
b. Measurable disease defined as showing new or progressive metastatic lymph node
and/or local recurrence or visceral metastatic disease (with the exception of 
metastases to the liver) on CT or MRI scans.
OR
c.
Radionuclide bone scan with at least 2 new bone lesions.
For Part B, at least approximately 40% of the participants to be enrolled must have at 
least 1 measurable lesion as defined by RECIST v1.1. 
19. Currently using a GnRH agonist or antagonist (unless surgically castrated).
20. Currently using a GnRH agonist or antagonist (unless surgically castrated).
21. No concurrent treatment with novel hormone therapy.
4.2. Exclusion Criteria for all Participants
Participants with any of the following characteristics/conditions will not be included in the
study:
1. Diagnosis of neuroendocrine prostate tumor or neuroendocrine tumor component.
2. Metastases to the brain or liver.
3. ECOG performance status (PS) 2.
4. History of prior malignancy other than prostate cancer within the past 3 years 
excluding successfully resected treated basal cell carcinoma or squamous cell 
carcinoma of the skin.
5. Major surgery within 4 weeks of first dose.
6. Radiation therapy within 4 weeks of starting study treatment, except: palliative or 
focal/limited radiotherapy to a limited field is allowed after consultation with the 
sponsor’s medical monitor at any time during study participation, including during 
screening.
7. Systemic anti-cancer therapy (including immunotherapy and chemotherapy) within 
4 weeks or 5 half-lives, whichever is shorter, prior to first dose.
8.
Sepuleucel-t and Prostvac within 12 months of first dose.
9. Receipt of an investigational agent within 30 days, prior to first dose.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 80
10. Receipt of an immunosuppressive dose of corticosteroids or other 
immunosuppressive medication (eg, methotrexate, rapamycin) within 30 days of first 
dose.  (Exceptions: Participants with adrenal insufficiency may take up to 5 mg of 
prednisone or equivalent daily.  Topical, nasal and inhaled corticosteroids are 
allowed).
11. History of or active autoimmune disorders (including but not limited to: myasthenia 
gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic 
lupus erythematosus, scleroderma.
12. Acetylcholine receptor binding antibody 0.5 nmol/L and/or abnormal neurologic 
examination at screening indicating possible underlying myasthenia gravis.
13. History of inflammatory bowel disease (eg, Crohn’s disease or ulcerative colitis), 
celiac disease, acute or chronic colitis, or other chronic gastrointestinal conditions 
associated with diarrhea.
14. Active and clinically significant bacterial, fungal or viral infection including 
hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) 
or acquired immunodeficiency syndrome (AIDS)-related illness. In equivocal cases
AIDS related-illness, subjects may be eligible if their viral load is negative.  HIV 
seropositive subjects who are healthy and low-risk for AIDS-related outcomes could 
be considered eligible.  Eligibility criteria for HIV-positive subjects should be 
evaluated and discussed with the sponsor’s medical monitor and will be based on 
current and past CD4 and T-cell counts, history (if any) of AIDS-defining conditions 
(eg, opportunistic infections), and status of HIV treatment. Also the potential for 
drug-drug interactions will be taken into consideration.
15. Any of the following in the previous 12 months or currently: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism, as well as ongoing cardiac dysrhythmias of NCI 
CTCAE Grade 2, atrial fibrillation of any grade, or QTc interval >470 msec at 
screening. 
16. Individuals in whom a skin-fold measurement of the cutaneous and subcutaneous 
tissue exceeds 40 millimeters (mm) for three or more designated electroporation of 
IM injection sites (ie, right or left deltoid or vastus lateralis muscles).
17. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate IM injection.
18. Current use of any implanted electronic stimulation device, including but not limited 
to cardiac pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, 
or deep brain stimulators.
19. Syncopal episode within 12 months of registration.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 81
20. Presence of any surgical or traumatic metal implants at all designated sites of 
administration.
21. Blood pressure >160/100 mmHg despite medical treatment.
22. Participation or plans to enroll in other studies involving investigational drug(s)
within 4 weeks prior to first dose. Participants may only continue to participate in the 
follow-up activities of another study if no interventional drug(s), blood collection, or 
treatment of any kind is involved.
23. Known or suspected hypersensitivity to any components of the PrCa VBIR regimen.
24. Other severe acute or chronic medical or psychiatric condition, including recent 
(within the past year) or active suicidal ideation or behavior, or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in the judgment of the investigator, would make the participant
inappropriate for entry into this study.
25. COVID-19/SARS-CoV2: SARS-CoV2 testing is not mandated for entry into this 
protocol. However, testing should follow local clinical practice standards and 
requirements.  A positive result on an approved test, even if the participant is 
asymptomatic, excludes a participant from this trial.
26. Participants who are investigational site staff members directly involved in the 
conduct of the study and their family members, site staff members otherwise 
supervised by the investigator, or participants who are Pfizer employees directly 
involved in the conduct of the study.
4.3. Lifestyle Guidelines
All male participants who are able to father children and are sexually active must agree to use 
a highly effective method of contraception consistently and correctly for the duration of the 
active treatment period and for at least 90 days after the last dose of investigational product.  
The investigator or his/her designee, in consultation with the participant, will confirm the 
most appropriate method of contraception for the individual participant from the permitted 
list of contraception methods (see below) and instruct the participant in its consistent and 
correct use.  Participants need to affirm that they meet at least one of the selected methods of 
contraception.  The investigator or his/her designee will discuss with the participant the need 
to use highly effective contraception consistently and correctly and document such 
conversation in the participant’s chart.  In addition, the investigator or his/her designee will 
instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant’s partner. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 82
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Female partner with an established use of oral, inserted, injected, or implanted 
hormonal methods of contraception is allowed provided the partner plans to remain 
on the same treatment throughout the entire study and has been using that hormonal 
contraceptive for an adequate period of time to ensure effectiveness.
2. Female partner with a correctly placed copper-containing intrauterine device (IUD). 
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
or suppository). 
4. Male sterilization with absence of sperm in the post vasectomy ejaculate.
5. Female partner who has undergone bilateral tubal ligation/bilateral salpingectomy or 
bilateral tubal occlusive procedure (provided that occlusion has been confirmed in 
accordance with the device’s label).
6. Female partner who meets the criteria for non-childbearing potential, defined as:

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed by having a serum 
follicle-stimulating hormone (FSH) level within the laboratory’s reference range 
for postmenopausal women.
4.4. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the Study Manual.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational compound identifiers, participant study 
numbers, contact information for the investigational site, and contact details for a contact 
center in the event that the investigational site staff cannot be reached to provide advice on a
medical question or problem originating from another healthcare professional not involved in 
the participant’s participation in the study.  The contact number can also be used by 
investigational staff if they are seeking advice on medical questions or problems; however, it 
should be used only in the event that the established communication pathways between the 
investigational site and the study team are not available.  It is therefore intended to augment, 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 83
but not replace, the established communication pathways between the investigational site and 
the study team for advice on medical questions or problems that may arise during the study.  
The contact number is not intended for use by the participant directly, and if a participant
calls that number, he or she will be directed back to the investigational site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines investigational product is defined as a pharmaceutical form of an active ingredient 
or placebo being tested or used as a reference in a clinical trial, including a product with a 
marketing authorization when used or assembled (formulated or packaged) in a way different 
from the approved form, or when used for an unapproved indication, or when used to gain 
further information about an approved use (ICH E6 1.33).
5.1. Allocation to Treatment
Eligible participants will be enrolled to receive components of the PrCa VBIR in an 
open-labeled, unblinded manner.  In Part A, participants will be successively assigned to the 
next available treatment slot at a dose level decided on after the previous cohort’s safety 
evaluation and ongoing observations of earlier enrolled participants. 
Dose level allocation will be performed by the sponsor after participants have given their 
written informed consent and have completed the necessary baseline assessments. The site 
staff will email a completed Registration Form to the designated sponsor study team member.  
The sponsor will assign a participant identification number documenting participant
enrollment.
No participant shall receive investigational product until the investigator or designee has 
received the following information in writing from the sponsor:

Confirmation of the participant’s enrollment.

Specification of the dose level for that participant.

Permission to proceed with dosing the participant.
The sponsor or designee will notify the other sites of the inclusion of a new participant, and 
will inform study sites about the next possible enrollment date.
5.2. Participant Compliance
All doses of adenovirus, pDNA, tremelimumab and PF-06801591 will be administered by the 
appropriately designated study staff at the investigational site.  The site will complete the
required dosage Preparation Record located in the Study Manual.  The use of the Preparation 
Record is preferred but it does not preclude the use of an existing appropriate clinical site 
documentation system.  The existing clinical site's documentation system should capture all 
pertinent/required information on the preparation and administration of the dose.  This may 
be used in place of the Preparation Record after approval from the Pfizer monitor. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 84
5.3. Investigational Product Supplies
All components of PrCa VBIR (PF-06753512) will be supplied by Pfizer.  The PrCa VBIR 
consists of the following components: Adenovirus (AdC68), plasmid DNA (pDNA), 
tremelimumab.  Sites will be provided with the following supplies:

PF-06755992 Adenovirus Solution for Injection 2 x 1011 VP/mL (AdC68).

PF-06755990 Plasmid Solution for Injection 2.50 mg/mL (pDNA).

PF-06753388 Tremelimumab Solution for Injection 100 mg/mL.

TDS-IM electroporation device and associated supplies (eg, cartridges) for pDNA 
administration.

PF-06801591 Solution for Injection 50 mg/mL.
Study centers will receive a supply of clinical trial materials upon site activation with 
instructions on how to confirm drug receipt.  Resupplies will be made during the course of 
the study based on need.  Study centers will supply commonly available sterile syringes and 
needs for IM and SC administration.  The details on drug supply will be provided in the 
Investigational Product Manual (IP Manual).  The study monitor should be contacted for any 
issues related to drug supplies.
5.3.1. Dosage Form(s) and Packaging
PF-06755992 Adenovirus Solution for Injection is presented as a sterile solution for 
intramuscular administration.  Each vial contains AdC68 at 2 x 1011 VP/mL in an aqueous 
buffered solution.  Each vial is filled with an adequate volume to eject 1 mL from a syringe 
with an IM needle attached.  The vial is sealed with a stopper and an overseal and labeled 
according to local regulatory requirements. 
PF-06755990 Plasmid Solution for Injection is presented as a sterile solution for 
intramuscular administration.  Each vial contains pDNA at 2.5 mg/mL in aqueous buffered 
solution.  The vial is filled with an adequate volume to eject 1 mL from the identified syringe
and IM needle.  The vial is sealed with a coated stopper and an overseal and labeled 
according to local regulatory requirements.
Each TDS-IM cartridge, for unique use, for administration of the pDNA plasmid solution 
will be supplied in sterile pouch (one cartridge/pouch) labeled according to local regulatory 
requirements.
PF-06753388 Tremelimumab Solution for Injection is presented as a sterile solution.  Each 
vial contains tremelimumab at 100 mg/mL in aqueous buffered solution.  The vial is filled 
with an adequate volume to eject 0.75 mL from a syringe with a SC needle attached.  The 
vial is sealed with a coated stopper and an overseal and labeled according to local regulatory 
requirements.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 85
PF-06801591 50 mg/mL injection is presented as a sterile solution.  Each vial contains 
100 mg of PF-06801591 in 2 mL of aqueous buffered solution, with a nominal volume of 
2.25 mL.  Each vial is sealed with a coated stopper and an overseal, and labeled according to 
local regulatory requirements.
5.3.2. Preparation and Dispensing
Adenovirus, pDNA, tremelimumab and PF-06801591 are provided as single use vials, and
will be packaged and dispensed in cartons with tamper evident seals.  The cartons should not 
be opened until the drug is to be administered.  For the adenovirus, pDNA, tremelimumab
and PF-06801591, see the Investigational Product (IP) manual for instructions on how to 
prepare the investigational products for administration.
Investigational product should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, 
practitioner, pharmacist, or medical assistant) as allowed by local, state, and institutional 
guidance.
5.4. Administration
All AdC68 intramuscular injections are given bilaterally.  AdC68 will be administered on 
Day 1 of Cycles 1 and 2.  Please refer to the IP manual for full instructions on the dosage and
administration.
pDNA intramuscular injections are given bilaterally.  pDNA will be administered beginning 
on Day 29 of Cycles 1 and 2 and will then be given at 4 week intervals.  After Cycle 2, 
pDNA will continue to be administered every 2 months in the Maintenance Treatment 
Period.  Please refer to the IP manual for full instructions on the dosage and administration of 
the pDNA and to the TDS-IM Instructions for Use document for the set up and use of the 
electroporation device.  The TDS-IM device should be operated by clinical personnel that 
have completed the necessary training on device operation.
All IM injections (AdC68 and pDNA) will be given bilaterally in the deltoid muscles or in 
the vastus lateralis muscles of the quadriceps.  Preference should be given to the vastus 
lateralis muscles when possible.
Tremelimumab will be administered bilaterally subcutaneously at 4 week intervals during 
Cycles 1 and 2 on the same day as the AdC68 or pDNA dosing beginning with Cohort 3A as 
described in the STUDY DESIGN section.  After Cycle 2, tremelimumab will continue to be 
administered every 2 months in the Maintenance Treatment Period.  Both AdC68 or pDNA 
injections should be given prior to tremelimumab administration.  Please refer to the IP 
manual for full instructions on the dosage and administration of tremelimumab.  
Tremelimumab is to be administered in close proximity to the vaccination site.  If the 
vaccination is administered in the vastus lateralis, the tremelimumab is to administered 
subcutaneously in either the lower quadrants of the abdomen or the quadriceps.  If the 
vaccination is administered in the deltoid, the tremelimumab is to be administered 
subcutaneously bilaterally in the outer triceps.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 86
PF-06801591 will be administered bilaterally subcutaneously at 4 week intervals on the same 
day as the AdC68 or pDNA and tremelimumab during Cycles 1 and 2 beginning with 
Cohort 6A as described in the STUDY DESIGN section.  The AdC68 or pDNA as well as 
the tremelimumab doses should be given prior to PF-06801591 administration.  During the 
Maintenance Treatment Period, participants in a cohort assigned to receive PF-06801591 will 
continue to be dosed with PF-06801591 at 4 week intervals.  Please refer to the IP manual for 
full instructions on the dosage and administration of PF-06801591.  PF-06801591 is to be 
administered in close proximity to the vaccination site.  If the vaccination is administered in 
the vastus lateralis, the PF-06801591 is to be administered subcutaneously bilaterally in the 
lower quadrants of the abdomen.  If the vaccination is administered in the deltoid, the 
PF-06801591 is to be administered subcutaneously bilaterally in the outer triceps.
5.4.1. Recommended Dose Modifications
Every effort should be made to administer investigational product on the planned dose and 
schedule.
In the event of significant toxicity, dosing may be delayed and/or reduced as described 
below.  In the event of multiple toxicities, dose modification should be based on the worst
toxicity observed.  Participants are to be instructed to notify investigators at the first 
occurrence of any adverse symptom.
Dose modifications may occur in one of three ways:

Within a cycle: dosing interruption until adequate recovery and dose reduction, if
required, during a given treatment cycle.

Between cycles: next cycle administration may be delayed due to persisting toxicity 
when a new cycle is due to start.

In the next cycle: dose reduction may be required in a subsequent cycle based on 
toxicity experienced in the previous cycle. 
5.4.2. Dosing Interruptions/Delays
Participants experiencing Grade 3 or 4 potentially treatment related toxicity or intolerable 
Grade 2 toxicity despite supportive care should have their treatment with all of the 
components interrupted/delayed.  Appropriate follow-up assessments should be done until 
adequate recovery occurs as assessed by the investigator.
Re-treatment following treatment interruption for treatment related toxicity may not occur 
until all of the following parameters have been met:

ANC 1,000/mm3.

Platelets count 50,000/mm3.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 87

Non-hematologic toxicities have returned to baseline or Grade 1 severity (or, at the 
investigator discretion, Grade 2 if not considered a safety risk for the patient).
If a treatment delay results from worsening of hematologic or biochemical parameters, the 
frequency of relevant blood tests should be increased as clinically indicated.  If these 
conditions are met within 2 weeks of treatment interruption or cycle delay, investigational 
product(s) may be resumed.  Refer to Section 5.4.4 for adverse events requiring dose 
reduction at the time of treatment resumption. 
If these parameters have not been met after 2 weeks of dosing interruption or 2 weeks of new 
cycle delay, permanent discontinuation of treatment should be considered.  Treatment 
resumption for participants recovering from treatment-related toxicity after >2 weeks of 
treatment interruption or cycle delay may be considered only if the participant is deemed to 
be deriving obvious clinical benefit per the investigator’s best medical judgment and needs to 
be agreed between the investigator and the sponsor.
5.4.3. Dosing Interruptions/Delays due to Non-Related Events 
If participants require treatment interruption for reasons other than treatment-related toxicity 
(eg, surgery) lasting >4weeks, treatment resumption should be decided in consultation with 
the Sponsor.  
In the event of active SARS-CoV2 infection confirmed (positive by regulatory 
authority-approved test) or presumed (test pending/clinical suspicion), the following criteria 
apply:

For symptomatic patients with active SARS-CoV2 infection, investigational 
treatment should be delayed for at least 14 days from start of symptoms.

This delay is intended to allow resolution of symptoms of SARS-CoV2 infection.

Prior to restarting treatment, the patient should be afebrile for 72 hours and 
SARS-CoV2-related symptoms should have recovered to ≤Grade 1 for a minimum of 
72 hours.

Inform the Sponsor prior to restarting treatment.

Consider potential drug-drug interactions (as described per study protocol) for any 
concomitant medication administered for treatment of SARS-CoV2 infection.
5.4.4. Dose Reductions
Following dose interruption or cycle delay due to toxicity, the investigational product(s) may 
need to be reduced when treatment is resumed.
No specific dose adjustments are recommended for Grade 1/2 treatment-related toxicity, 
unless otherwise specified.  However, investigators should always manage their participants 
according to their medical judgment based on the particular clinical circumstances.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 88
5.4.4.1. AdC68 Dose Reductions
Changes in the dose levels for AdC68 will be discussed with the sponsor.  Dose reduction of 
adenovirus by 1 dose level may be allowed depending on the type and severity of toxicity 
encountered.  In addition, an intermediate dose may be considered.  Participants requiring a 
dose level lower than the starting dose will be discontinued from treatment and enter into the 
follow-up phase unless otherwise agreed between the investigator and sponsor.  All dose 
modifications/adjustments must be clearly documented in the participant’s source notes and 
CRF.
Table 1.
Adenovirus Available Dose Levels
Dose Level
Adenovirus*
Starting
4 x 1011 VP
+1
6 x 1011 VP
* Intermediate doses may also be considered upon discussion with the 
sponsor.
Table 2.
Dose Modifications for Adenovirus Related Toxicity
Toxicity
Grade 1/2
Grade 3
Grade 4
Non-hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 1, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce the 
dose by 1 level at the discretion of 
the investigator*.
Discontinue treatment.
Hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 2, or has returned to 
baseline, then resume treatment at 
the same dose level.
Discontinue treatment.
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
5.4.4.2. Tremelimumab Dose Reductions
Changes in the dose levels for tremelimumab will be discussed with the sponsor.  For cohorts 
where PrCa VBIR will be administered alone, dose reduction of tremelimumab by 1 dose 
level may be allowed depending on the type and severity of toxicity encountered.  For 
cohorts where PrCa VBIR will be given in combination with PF-06801591, dose reductions 
of tremelimumab by 1 dose level will be allowed.  In addition, an intermediate dose may be 
considered.  Participants requiring a dose level lower than 40 mg will be discontinued from 
treatment and enter into the follow-up phase unless otherwise agreed between the 
investigator and sponsor.  Algorithms for the management of suspected pulmonary, GI, liver, 
endocrine, skin, neurological and renal toxicities have been developed (See Appendix 7).  All 
dose modifications/adjustments must be clearly documented in the participant’s source notes 
and CRF.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 89
Once a dose has been reduced for a given participant, all subsequent doses should be 
administered at that dose level, unless further dose reduction is required.  Dose re-escalation 
for tremelimumab is not allowed.
If a participant experiences a Grade ≥3 toxicity or an intolerable side effect, withhold dosing 
for one week or until symptoms improve to Grade ≤2, then resume at the same or a reduced 
dose (120 mg or 80 mg), if warranted.
Table 3.
Tremelimumab Available Dose Levels
Dose Level
Tremelimumab*
-1
40 mg
Starting
80 mg**
* Intermediate doses may also be considered upon discussion with 
the sponsor.
** Dose lower than 80 mg may be evaluated based on emerging 
safety data. 
Table 4.
Dose Modifications for Tremelimumab Related Toxicity When Given in 
Combination with AdC68 or pDNA 
Toxicity
Grade 1/2
Grade 3
Grade 4
Non-hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 1, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce the 
dose by 1 level at the discretion of 
the investigator*.
Discontinue treatment.
Hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 2, or has returned to 
baseline, then resume treatment at 
the same dose level.
Discontinue treatment.
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
5.4.4.3. PF-06801591 Dose Reductions
Events including, but not limited to, pneumonitis, colitis, creatinine and liver function test 
(LFT) elevation should be monitored carefully with this class of agents.  Changes in the dose 
levels for PF-06801591 may be allowed depending on the type and severity of toxicity 
encountered.  Dose reductions may be required for PF-06801591, tremelimumab or 
potentially both compounds depending on the event and the severity.  After a dose 
interruption, it is acceptable to resume dosing with the PrCa VBIR alone, and
PF-06801591 treatment to resume at the next planned dosing.  Dose reductions of 
PF-06801591 by 1 dose level may be allowed, including dose reductions below the starting 
dose.  In addition an intermediate dose may be considered.  All dose 
modifications/adjustments must be clearly documented in the participant’s source notes and 
CRF.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 90
Table 5.
PF-06801591 Available Dose Levels
Cohort 
Starting Dose*
Level -1**
3B
300 mg
130 mg
5B
130 mg
75 mg
* The starting dose may be modified based on emerging safety data.  See 
Section Clinical PF-06801591 Dosing for additional details. 
** Intermediate doses may also be considered upon discussion with the sponsor.
Table 5 describes the recommended dose modification for PF-06801591 treatment-associated
toxicity. Algorithms for the management of suspected pulmonary, GI, liver, endocrine, skin, 
neurological and renal toxicities have been developed (See Appendix 7).
Participants requiring >2 weeks of dose interruption should be considered for discontinuation 
of treatment with PF-06801591.  Participants may be allowed to resume dosing with the PrCa 
VBIR alone rather than in combination with PF-06801591 for one dose with plans to resume 
dosing with PF-06801591 at the next dosing timepoint if agreed upon by the investigator and 
sponsor.  This would result in more than 2 weeks of dose interruption.  Participants who 
discontinue PF-06801591 due to toxicity will be allowed to remain in the study and continue 
treatment with the other components.
The following serves as demonstrating general rules.  Action may differ in specific cases 
based on evaluation by the investigator and the sponsor.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 91
Table 6.
Dose Modifications for PF 06801591 and/or Tremelimumab (When Given
in Combination With PF 06801591) Related Toxicity
Toxicity
Grade 1
Grade 2
Grade 3
Grade 4
Non-hematologic
Continue at the 
same dose level.
For pneumonitis, 
endocrinopathy, colitis, 
creatinine, AST, ALT, 
or total bilirubin 
elevations, withhold 
dose until toxicity is 
Grade ≤1, or has 
returned to baseline, 
then resume at the same 
dose level or reduce by 
1 level (considering 
each compound 
separately) at the 
discretion of the 
investigator.
For all other events, 
continue at the same 
dose level.
For pneumonitis, colitis, 
endocrinopathy, 
creatinine, AST, ALT or 
total bilirubin elevations,
or pruritus discontinue 
treatment.**
For all other events 
withhold dose until
toxicity is Grade 1, or 
has returned to baseline, 
then resume treatment at 
the same dose level or 
reduce the dose by 
1 level (considering each 
compound separately) at 
the discretion of the 
investigator.*  Treatment 
may resume with the 
PrCa VBIR with an 
interruption of 
PF-06801591 for one 
dose at the discretion of 
the investigator. 
Discontinue 
treatment.**
Hematologic
Continue at the 
same dose level.
Continue at the same 
dose level.
Withhold dose until 
toxicity is Grade 2, or 
has returned to baseline, 
then resume treatment at 
the same dose level.
Discontinue 
treatment.**
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
** For Grade >3 colitis or pneumonitis, discontinue treatment permanently. For any grade of myocarditis 
discontinue treatment permanently. For all other conditions participants may remain in the study and 
resume therapy once toxicity has returned to Grade ≤1 or baseline, after discussion with the Sponsor.
5.5. Investigational Product Storage
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Upon receipt at the site, all drug product should be immediately transferred, in its original 
container, to the appropriate monitored storage area.  Current storage conditions for 
AdC68 vials are frozen (-20C5C).  The current storage conditions for the pDNA,
tremelimumab and PF-06801591 are refrigerated (2-8C).  Storage conditions stated in the 
single reference safety document (eg, Investigator’s Brochure) will be superseded by the 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 92
storage conditions stated in the labeling.  Please see the Instructions for Use for details on 
storage of the TDS-IM device.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation 
for excursions should be documented.  The operation of the temperature monitoring device 
and storage unit (for example, refrigerator), as applicable, should be regularly inspected to 
ensure it is maintained in working order. 
Any excursions from the product label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to storage conditions as 
described in the labeling, as soon as possible.  Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the sponsor. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  It 
will not be considered a protocol deviation if the sponsor approves the use of the 
investigational product after the temperature excursion.  Use of the investigational product 
prior to sponsor approval will be considered a protocol deviation.  Specific details regarding 
information the site should report for each excursion will be provided to the site. 
5.6. Investigational Product Accountability
All investigational product must be kept in a locked, limited access room.  The 
investigational product and electroporation device must not be used outside of the context of 
this protocol.  The investigator’s site must maintain adequate records documenting the 
receipt, use, loss, or other disposition of the investigational product supplies.  To ensure 
adequate records, all components of PrCa VBIR as well as PF-06801591 will be accounted
for in the drug accountability inventory forms as instructed by the sponsor.
5.6.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the study site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer,  and all destruction must be adequately documented.
5.7. Concomitant Treatment(s)
Concomitant treatment considered necessary for the participant’s well-being may be given at 
the discretion of the treating physician.
Prophylactic antipyretics and other pain medications to prevent symptoms associated with 
investigational vaccine administration are not permitted.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 93
All concomitant treatments, blood products, as well as non-drug interventions received by 
participants from screening until the end of study visit will be recorded on the Case Report 
Form (CRF). 
5.7.1. Prohibited Concomitant Vaccines
No vaccines (licensed or investigational) other than study vaccine, influenza and 
pneumococcal vaccines should be given during the study within 30 days prior to or after 
dosing.  Other vaccines may be administered only if medically necessary (eg, tetanus post 
exposure prophylaxis).
For participants who receive tremelimumab, live attenuated vaccines should not be 
administered within 30 days prior to or after dosing with tremelimumab.  The administration 
of inactivated vaccines is allowed. 
5.7.2. Other Anti-tumor/Anti-cancer or Experimental Drugs
No additional anti-tumor treatment will be permitted while participants are receiving study 
treatment. Additionally, the concurrent use of vitamins or herbal supplements for an 
anticancer treatment is not permitted. 
Participants currently being treated with a GnRH agonist or antagonist may continue 
treatment while participating in this study as long as the GnRH agonist treatment has been 
well tolerated for at least three months prior to study entry.
5.7.3. Participants on beta blockers
Per the TDS-IM Investigator’s Brochure (28-Jun-2019), two cases of syncope have been 
reported in association with the device in a total of over 800 subjects receiving up to 
5 administrations.  Caution should be undertaken during injections in participant taking beta 
blockers. Strong consideration should be given to placing the participant in prone position 
depending on the participant’s medical condition. 
5.7.4. Supportive Care 
Palliative and supportive care for disease related symptoms may be administered at the 
investigator’s discretion and according to any available American Society of Clinical 
Oncology (ASCO) guidelines. 
Participants currently being treated with denosumab or bisphosphonates (eg, zoledronate) for
bone disease may continue treatment while participating in this study.  However, initiation of 
treatment with these types of compounds should be avoided while participating in the study.
5.7.5. Anti-Diarrhea and Anti-Emetic Therapy
Primary prophylaxis of diarrhea, nausea and vomiting is not permitted prior to the first dose 
of adenovirus, tremelimumab and/or PF-06801591.  Primary prophylaxis on subsequent 
dosing days is at the investigator’s discretion.  The choice of the prophylactic drug is up to 
the investigator with sponsor approval and assuming the drug is not included in the 
Concomitant Treatment(s) section, as well as the duration of treatment assuming there is no 
known or expected drug-drug interaction.  If so, then it must be approved by the sponsor.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 94
5.7.6. Anti-inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed assuming there is no 
known or expected drug-drug interaction and assuming the drug is not included in the 
Concomitant Treatment(s) section.
5.7.7. Therapy for Treatment of Pyrexia and Flu-like Symptoms
Primary prophylaxis of fever or flu-like symptoms is not permitted prior to dosing of 
adenovirus.  Following receipt of adenovirus, medications used to treat fever or flu-like 
symptoms (eg, acetaminophen, ibuprofen) should be administered at the first sign of either 
event.
5.7.8. Corticosteroids
Chronic, systemic corticosteroid use for palliative or supportive purpose is not permitted.  
The short term use of corticosteroids for medically indicated conditions is allowed and 
should be discussed with the sponsor.  Topical, nasal and inhaled corticosteroids are allowed.
5.7.9. Surgery
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and administration of the PrCa VBIR 
components or combination agents required to minimize the risk of impaired wound healing 
and bleeding has not been determined.  Stopping all components of PrCa VBIR, 
PF-06801591 is recommended at least 7 days prior to surgery.  Postoperatively, the decision 
to reinitiate treatment should be based on a clinical assessment of satisfactory wound healing 
and recovery from surgery.
6. STUDY PROCEDURES
6.1. Screening
For screening procedures see Schedule of Activities and ASSESSMENTS section.
6.2. Study Period
For treatment period and maintenance treatment period procedures, see Schedule of 
Activities and ASSESSMENTS section.
6.3. Follow-up Period
Patients who have permanently discontinued treatment with the study drugs will complete the 
assessments required for the End of Treatment visit and then enter the follow-up period 
which includes 6 months of additional evaluations. For follow-up procedures see 
Schedule of Activities and ASSESSMENTS section.
6.4. Patient Withdrawal
Participant withdrawal may include either: (a) withdrawal from treatment with continued 
follow up, or (b) withdrawal from treatment and no further follow up. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 95
6.4.1. Withdrawal from Treatment
Participants may withdraw from treatment at any time at their own request, or they may be 
withdrawn from treatment at the discretion of the Investigator or Sponsor for the following 
reasons: (a) safety, (b) lack of efficacy, (c) behavioral reasons, or (d) the inability of the 
participant to comply with the protocol-required schedule of study visits or procedures at a 
given study site.  Reasons for withdrawal of study treatment may include:

Objective disease progression by irRECIST (see Appendix 4).  Disease progression 
will be confirmed with two consecutive timepoints at least 4 weeks (or at least 
6 weeks for progressing disease on bone scan) apart in the absence of rapid clinical 
deterioration;

Global deterioration of health status requiring discontinuation;

Unacceptable toxicity, including treatment-related DLT;

Significant protocol violation;

Lost to follow-up (defined as: If a participant repeatedly fails to return for scheduled 
visits and repeated attempts to contact the patient have been unsuccessful);

Participant refused further treatment;

Study terminated by sponsor;

Death.
6.4.2. Wtihdrawal from Study 
Reasons for withdrawal from study follow-up may include:

Completed study follow-up;

Study terminated by sponsor;

Lost to follow-up (defined as: If a participant repeatedly fails to return for scheduled 
visits and repeated attempts to contact the patient have been unsuccessful);

Refused further follow-up;

Death.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant. All attempts to contact the participant and information received during 
contact attempts should be documented in the participant’s medical record. In any 
circumstance, every effort should be made to document participant outcome, if possible.  The 
investigator should request that the participant return for a final visit, if applicable, and 
follow-up with the participant regarding any unresolved AEs.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 96
If the participant refuses further visits, no further study specific evaluations should be 
performed, and no additional data should be collected.  The sponsor may retain and continue 
to use any data collected before such withdrawal of consent. Publicly available information 
may be used to determine follow up information as appropriately directed in accordance with 
local law. 
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator, which may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the participant. When a protocol-required test cannot be performed, 
the investigator will document the reason for this and any corrective and preventive actions 
that he or she has taken to ensure that normal processes are adhered to as soon as possible. 
The study team will be informed of these incidents in a timely fashion.
7.1. Safety Assessments
Safety assessments will include collection of adverse events (AEs), serious adverse events 
(SAEs), vital signs and physical examination, electrocardiogram (ECG (12 lead)), laboratory 
assessments, and verification of concomitant treatments.
7.1.1. Adverse Events
Assessment of adverse events will include the type, incidence, severity (graded by the NCI 
CTCAE version 4.03) timing, seriousness, and relatedness.
Adverse events that occur during the study will be recorded on the adverse events CRF page.
7.1.2. Laboratory Safety Assessment
Hematology, blood chemistry and coagulation will be drawn at the time points described in 
the Schedule of Activities and analyzed at local laboratories.
Hematology
Chemistry
Coagulation
Urinalysis
Hemoglobin
ALT
PT or INR
Urine dipstick for urine 
protein: If positive collect 
24-hr and microscopic 
(Reflex Testing)
Platelets
AST
PTT
WBC
Alk Phos
Absolute Neutrophils
Sodium
Absolute Lymphocytes
Potassium
Absolute Monocytes
Magnesium
Urine dipstick for urine 
blood: If positive collect a 
microscopic (Reflex 
Testing)
Absolute Eosinophils
Chloride
Absolute Basophils
Total Calcium
Total Bilirubin1
BUN or Urea
Creatinine
Uric Acid
Glucose (non-fasted)
Albumin

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 97
Hematology
Chemistry
Coagulation
Urinalysis
Phosphorous or Phosphate
Lactate dehydrogenase
Lipase
Amylase
Bicarbonate or carbon 
dioxide
Total protein
TSH (if abnormal, reflex 
free T4 and free T3 tests)2
1. For Hy's law potential cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, 
prothrombin time (PT)/INR, alkaline phosphatase, total bile acids and acetaminophen drug and/or protein 
adduct levels.
2. For participants in Cohorts 6A through 9A and Cohorts 3B and 5B.
7.1.3. Vital Signs, Physical Examination and Skin Assessment
Participants will have a physical examination to include weight, vital signs, assessment of 
ECOG performance status and height; height will be measured at screening only.
A complete physical examination (PE) will be performed at Screening and at the End of 
Treatment visit for each participant and will include an assessment of all body systems 
(genitourinary examination is optional).  A neurologic examination must be conducted at 
Screening to look for potential signs suggestive of autoimmune disorders.  Findings of all 
physical examinations should be recorded in the source documents, and any change from 
baseline considered by the investigator to be clinically significant should be recorded as an 
adverse event in the CRF.
Abbreviated PEs should be performed as appropriate per the Schedule of Activities (SOA), 
and on an as needed basis for assessment of adverse events.  Abbreviated exams should be 
targeted to specific symptoms or complaints and be consistent with local standard of care. 
However, a neurologic examination must be performed during each exam conducted during 
Cycle 1.
Weight and body surface area (BSA) do not need to be performed at each visit; however 
participants should be monitored throughout the study for significant weight change. 
Vital signs will include measurements of blood pressure and temperature (oral, temporal, 
tympanic or axillary). On dosing days, vital signs should be measured prior to administration 
of any of the study treatments. Sitting blood pressure (BP) will be measured with the 
participant’s arm supported at the level of the heart and recorded to the nearest mmHg 
sufficient.  The same arm (preferably the dominant arm) should preferably be used 
throughout the trial.  A blood pressure cuff, which has been properly sized and calibrated, 
should be used to measure blood pressure.  The use of automated devices for measuring BP 
is acceptable. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 98
Assessment of the skin and subcutaneous tissue thickness at the eligible administration sites 
will be performed at screening as described in the TDS-IM Instructions for Use.  The 
assessment procedure does not need to be repeated during the course of the study unless the 
participant experiences a greater than 10% change in body mass relative to screening.
7.1.4. (12-Lead) ECG
Electrocardiogram (ECG): Triplicate 12-lead (with a 10-second rhythm strip) tracing will be 
used for all ECGs.  It is preferable that the machine used has a capacity to calculate the 
standard intervals automatically.  At each time point (see the Schedule of Activities), three 
consecutive ECGs will be performed at approximately 2 minutes apart to determine the mean 
QTcF interval.  If the mean QTcF is prolonged (value of >500 msec), the ECGs should be 
re-evaluated by a qualified person at the institution for confirmation.  If manual reading
verifies a QTcF of >500 msec, immediate correction for reversible causes (including 
electrolyte abnormalities, hypoxia and concomitant medications for drugs with the potential 
to prolong the QTcF interval) should be performed.  In addition, repeat ECGs should be 
immediately performed hourly for at least 3 hours until the QTcF interval falls below 
500 msec. If QTcF interval reverts to less than 500 msec, and in the judgment of the 
investigator(s) and sponsor is determined to be due to cause(s) other than investigational 
product, treatment may be continued with regular ECG monitoring.  If in that timeframe the 
QTcF intervals rise above 500 msec the investigational product will be held until the QTcF 
interval decreases to 500 msec.  Participants will then re-start the investigational product at 
the next lowest dose level.  If the QTcF interval has still not decreased to 500 msec after 
2-weeks, or if at any time a participant has a QTcF interval >515 msec or becomes 
symptomatic, the participant will be removed from the study.  Additional triplicate ECGs 
may be performed as clinically indicated. 
Prior to concluding that an episode of prolongation of the QTcF interval is due to 
investigational product, thorough consideration should be given to potential precipitating 
factors (eg, change in participant clinical condition, effect of concurrent medication, 
electrolyte disturbance) and possible evaluation by specialist.
If participant experiences a cardiac or neurologic AE (specifically syncope, dizziness, 
seizures, or stroke), an ECG (triplicate) should be obtained at the time of the event. 
7.1.5. Monitoring for Potential Immune Mediated Endocrinopathies
Participants will be monitored for clinical signs and symptoms of hypophysitis, adrenal 
insufficiency (including Addisonian crisis), and hyper- or hypothyroidism.  Laboratory 
evaluation will be performed as clinically indicated based on symptoms.  For example, the 
development of symptoms of adrenal insufficiency, such as unexplained nausea, vomiting 
and hypotension, would trigger prompt evaluation (Cosyntropin Stimulation Testing) and 
treatment (systemic glucocorticoids).  Symptoms suggestive of an inflammatory pituitary 
process with mass effect, such as diplopia, visual field abnormalities and severe headache, 
call for urgent pituitary imaging and evaluation for hypopituitarism, with specific attention to 
the pituitary-adrenal axis.  Symptoms of disordered thyroid metabolism, such as changes in 
bowel frequency, fatigue, unexplained weight loss or gain should prompt evaluation of 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 99
thyroid function tests, with a focus on free thyroid hormone levels (T3 and T4) given the 
possibility that thyroid stimulating hormone levels may be unreliable due to 
immune-mediated pituitary dysfunction.
7.1.6. Acetylcholine Receptor Testing
A blood sample will be collected at screening for central evaluation of AChR antibodies.  
 
  Treatment 
decisions will be made based on the clinical diagnosis.
7.1.7. Cardiac Safety Monitoring
The algorithm for cardiac Safety Monitoring is shown in Figure 2 below. 
For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must 
be measured and found to be within the normal reference range within 28 days before study 
entry, preferably using the central laboratory kits provided. Dosing should not proceed until 
results within the normal reference range have been received by the Investigator. For any 
results above of the normal reference range (even if borderline), the participant should be 
referred to a cardiologist by the Investigator for complete cardiac workup and repeat cardiac 
troponin. The participant can only enter the study after cardiac evaluation, troponin findings 
within the normal reference range, cardiac clearance and with approval of the Sponsor. 
For participants ongoing in the study, circulating levels of cardiac Troponin-I (cTnI) must be 
measured within 10 days of dosing on the days shown in the SOA (ie, C1D29, C1D57, 
C1D85, C2D1, C2D57, month 9 and month 12) and found to be within the normal reference 
range. No dosing of participants can occur unless the cTnI is within the normal reference 
range. For any results above the normal reference range (even if borderline) the participant 
must be referred by the Investigator to a cardiologist for complete work-up and repeat cTnI. 
Dosing can only occur after cardiac evaluation, cTnI findings within the normal reference 
range, cardiac clearance and with approval of the Sponsor. 
While central laboratory testing for cTnI is preferred, it requires a minimum of 3 days to 
return results. Therefore, local laboratory testing of cTnI may be used, but only if the timing 
of measuring cTnI by the central laboratory test (minimum 3 day turnaround time) puts an 
undue burden or risk on the participant. The use of cardiac troponin-T is strongly 
discouraged, but could be used in place of cTnI if the central laboratory test puts an undue 
burden or risk on the participant.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 100
Figure 2.
Cardiac Safety Monitoring Algorithm
7.2. Pharmacokinetics Assessments
7.2.1. Serum for Assessment of Tremelimumab Pharmacokinetics
Blood samples (approximately 3 mL whole blood) to provide at least 1 mL of serum for 
measurement of serum tremelimumab concentrations will be collected from participants 
enrolled into Cohorts 3A or later at the time points specified in the SOA.  PK sampling 
schedule may be modified based on emerging PK data. 
In addition to samples collected at the scheduled times, an additional blood sample for 
determination of tremelimumab PK should be collected from participants experiencing 
unexpected and/or serious AE’s and the date and time of blood sample collection and of last 
dosing prior to PK collection documented in the CRF.
All efforts will be made to obtain the tremelimumab PK samples at the scheduled nominal 
time relative to dosing.  However, samples obtained within the protocol specified time 
window will not be captured as a protocol deviation, as long as the exact time of the sample 
collection is noted on the source document and data collection tool (eg, CRF).  If a scheduled 
blood sample collection cannot be completed for any reason, the missed sample time may be 
re-scheduled with agreement of clinical investigators, participant and sponsor.
Details regarding the collection, processing, storage and shipping of tremelimumab 
PK samples will be provided in the study manual.
Tremelimumab PK samples will be assayed using a validated analytical method in 
compliance with Pfizer standard operating procedures. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 101
As part of the understanding of the PK of the investigational product, tremelimumab samples 
may be used for evaluation of the bioanalytical methods of tremelimumab.  
 
7.2.2. Serum for Assessment of PF-06801591 Pharmacokinetics
Blood samples (approximately 5 mL) to provide serum for the analysis of 
PF-06801591 concentrations will be collected from participants enrolled into Cohorts 6A 
through 9A or Dose Expansion Cohorts 3B and 5B at the time points specified in the SOA.  
PK sampling schedule may be modified based on emerging PK data.
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from participants experiencing unexpected and/or serious AE’s and the date and 
time of blood sample collection and of last dosing prior to PK collection documented in the 
CRF.
All efforts will be made to obtain PK samples at the scheduled nominal time relative to 
dosing.  However, samples obtained within the protocol-specified time window will not be 
captured as a protocol deviation, as long as the exact time of the sample collection is noted 
on the source document and data collection tool (eg, CRF).  If a scheduled blood sample 
collection cannot be completed for any reason, the missed sample time may be re-scheduled 
with agreement of the clinical investigator, participant, and sponsor.
Sample for PK analysis will be assayed for PF-06801591 using a validated analytical method 
in compliance with Pfizer standard operating procedures.  
 
These data will not be included in the clinical 
study report.  Details regarding the collection, processing, storage and shipping of the blood 
samples will be provided in the study manual.
 
 
 
 
 
 
CCI
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 102
7.3.1. Cellular Immune Assays
Blood samples of approximately 50 mL whole blood from all time points specified in the 
SOA will be collected in appropriate blood collection tubes to provide approximately 
50 million peripheral blood mononuclear cells (PBMC) for the assessment of tumor-antigen 
specific cellular immune responses from all participants from the study.  The whole blood in 
the appropriate collection tube will be transferred to a qualified local laboratory for the 
separation and cryopreservation of PBMC on Ficoll™gradients within 6 hours of blood 
draw.  Cryopreserved PBMC will be stored at the local laboratory prior to shipment to Pfizer 
for subsequent evaluation of cellular immune responses.  In addition, these samples may be 
used for evaluation of T cell receptor sequences or other exploratory assays.
Details regarding the collection, processing, storage and shipping of the PBMC samples will 
be provided in the study manual.  The PBMC processing laboratory will be qualified to 
separate and store PBMC samples in accordance with Pfizer standard operating procedures.
PBMC samples will be assayed for cellular immune responses against PSMA, PSCA and 
PSA antigens using qualified analytical methods in compliance with Pfizer standard 
operating procedures. Other antigens from potential epitope spreading or antigen cascading 
may also be analyzed.
 
 
 
  
 
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 103
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 104
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Assessment of response will be made using RECIST version 1.1 (Appendix 3) and irRECIST 
(Appendix 4) and PCWG3 criteria (Appendix 5) for bone disease. 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 105
All participants’ files and radiologic images must be available for source verification and for 
potential peer review. In addition, historical images (collected up to one year prior to study 
entry) may be requested for potential peer review.
7.5. Immunogenicity Evaluations
7.5.1. Tremelimumab Immunogenicity Evaluations
Blood samples (approximately 5 mL) to provide at least 2 mL of serum to detect ADA and 
neutralizing antibody (Nab) against tremelimumab (~1 mL each of ADA and Nab) will be 
collected from participants enrolled in to Cohorts 3A to 9A and Cohorts 1B to 5B at the 
times specified in the SOA. 
Details regarding the collection, progressing, storage and shipping of the blood samples will 
be provided in the Study Manual.
The tremelimumab ADA and Nab samples will be analyzed using validated analytical 
methods in compliance with Pfizer standard operating procedures. The ADA sample 
analysis will follow a tiered approach of screening, confirmation, and titer determination.  
Only those samples tested positive for ADA will be further tested for Nab.
 
7.5.2. PF-06801591 Immunogenicity Evaluations
Blood samples (approximately 5 mL) to provide at least 2 mL of serum for detection of ADA 
and Nab against PF-06801591 (~1 mL each for ADA and Nab) will be collected from 
participants enrolled in Cohorts 6A to 9A and Cohorts 3B and 5B into appropriately labeled 
tubes at times specified in the SOA.  Additional instructions for sample collection, 
processing, storage, and shipping will be provided in the lab manual.
The ADA samples will be analyzed using a validated assay in compliance with Pfizer 
standard operating procedures.  The sample analysis will follow a tiered approach of 
screening, confirmation, and titer determination.  Samples tested positive for ADA will be 
further analyzed for Nab using a validated assay in compliance with Pfizer standard 
operating procedures. 
 
 
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 106
7.6. Banked Biospecimens
7.6.1. Markers of Drug Response 
Studying the variation in genetic markers and other biomarkers may help to explain some of 
the variability in response seen with some drugs among different individuals.  This is referred 
to as pharmacogenomic/biomarker research.  Comparing the deoxyribonucleic acid (DNA), 
ribonucleic (RNA), protein, and metabolite variation patterns of patients who respond well 
and those who respond poorly to treatment may help to better define the most appropriate 
group of patients in which to target a given treatment. 
 
 
 
 
 
 
 
To protect patients’ confidentiality, the banked biospecimens and data generated from them 
will be coded with the patient’s study identification (ID) number. Samples will be kept in a 
facility accessible only by swiping a badge. Data will be stored on password-protected 
computer systems. The key between the code and the patient’s personal identifiers will be 
held at the study site; the researchers using the biospecimens and data generated from them 
will not have access to the key nor any personally identifying information.  Biospecimens 
will be used only for the purposes described here and in the informed consent 
document/patient information sheet; any other uses require additional ethical approval.  
Unless a time limitation is required by local regulations or ethical requirements, 
biospecimens will be stored indefinitely to allow for future research on the topics described 
here, including research conducted during the lengthy drug development process and also 
postmarketing research.  Patients can withdraw their consent for the use of their 
biospecimens at any time by making a request to the investigator, in which case any 
remaining biospecimen will be destroyed; data already generated from the biospecimens will 
continue to be stored to protect the integrity of existing analyses.  It is very unlikely that
results generated from the biospecimens will have any clinical, diagnostic, or therapeutic 
implications for the individual study participants.  Patients are notified in the informed 
consent document/patient information sheet that their results will not be given to them, unless 
required by local laws or regulations, in which case results will be returned via the 
investigator.  Results will not be provided to family members or other physicians, nor will 
they be recorded in the patient’s medical record.  There is no intention to contact patients 
after completion of the clinical study.
A 4-mL blood biospecimen Prep D1 (K2 edetic acid (ethylenediaminetetraacetic 
acid)(EDTA)) whole blood collection optimized for DNA analysis) will be collected at the 
baseline visit to be retained for potential pharmacogenomic/biomarker analyses related to 
drug response, unless prohibited by local regulations or ethics committee decision.  For 
example, putative safety biomarkers, drug-metabolizing enzyme genes, drug-transport 
protein genes, or genes thought to be related to the mechanism of drug action may be 
examined.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 107
The banked biospecimens will be collected from all patients unless prohibited by local 
regulations or ethics committee decision.  Detailed collection, processing, storage, and 
shipment instructions are provided in the study manual.
It is possible that the use of these biospecimens may result in commercially viable products.  
Patients will be advised in the informed consent document/patient information sheet that they 
will not be compensated in this event.
7.6.2. Additional Research
Unless prohibited by local regulations or ethics committee decision, patients will be asked to 
indicate on the consent form whether they will allow the banked biospecimens to also be 
used for the following research:

Investigations of the disease under study in the clinical study, and related conditions.

Biospecimens may be used as controls.  This includes use in case-control studies of 
diseases for which Pfizer is researching drug therapies; use in characterizing the 
natural variation amongst people in genes, RNA, proteins, and metabolites; and use in 
developing new technologies related to pharmacogenomics/biomarkers. 
Patients need not provide additional biospecimens for the uses described in this section; the 
biospecimens specified in the Markers of Drug Response Section will be used.  Patients may 
still participate in the clinical study if they elect not to allow their banked biospecimens to be
used for the additional purposes described in this section. 
7.7. Other Assessments
7.7.1. Tumor and Medical History
History of the patient’s disease under study including details of the primary diagnosis and 
treatment history will be collected within 28 before the start of treatment.  In addition, a 
history of disease process other than the cancer under study (active or resolved) and 
concurrent illnesses will be collected.  This will also include prior treatments and any current 
medical treatments for any condition.
Also, the Gleason score at the time of the patient’s initial diagnosis and/or the time of the 
most current recurrence should be collected if the information is available.
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 108
AE.  The investigator is required to assess causality.  Follow-up by the investigator may be 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the patient provides informed consent, which is obtained prior to the patient’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including the 6 month follow-up period.  
SAEs occurring to a patient after the active reporting period has ended should be reported to 
the sponsor if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product are to be reported to the sponsor.
AEs (serious and non-serious) should be recorded on the CRF from the time the patient has 
taken at least 1 dose of investigational product through the patient’s last visit. 
If a patient begins a new anticancer therapy, the AE reporting period for non-serious AEs 
ends at the time the new treatment is started.  Death must be reported if it occurs during the 
SAE reporting period after the last dose of investigational product, irrespective of any 
intervening treatment.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation patient administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to: 

Abnormal test findings;

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 109

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasations;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure;

Worsening of signs and symptoms of the malignancy under study should be reported
as AEs in the appropriate section of the CRF.  Disease progression assessed by 
measurement of malignant lesions on radiographs or other methods should not be 
reported as AEs.
8.4. Medication Errors
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong patient, at the wrong time, or at the wrong dosage strength.  
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF, which is a specific version of the AE page, and on the SAE form when 
appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving patient exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating patient.
Whether or not the medication error should be accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page 
and, if applicable, any associated AEs are captured on an AE CRF page. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 110
8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing outside of the protocol-stipulated dose 
adjustments or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect;

Progression of the malignancy under study (including signs and symptoms of 
progression) should not be reported as an SAE unless the outcome is fatal within the 
safety reporting period.  Hospitalization due to signs and symptoms of disease 
progression should not be reported as an SAE.  If the malignancy has a fatal outcome 
during the study or within the safety reporting period, then the event leading to death
must be recorded as an AE and as an SAE with CTCAE) grade 5 (see the section on 
Severity Assessment).
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 111
Examples of such events are 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.
Medical device complaints may meet the SAE reporting requirement criteria (see the section 
on Medical Device Complaint Reporting Requirements).  An incident is any malfunction 
(ie, the failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a patient, or user, or of 
other persons, or to a serious deterioration in their state of health. 
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure; 

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items.
Examples: clinically relevant increase in the duration of a surgical procedure; a condition that 
requires hospitalization or significant prolongation of existing hospitalization.

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.6.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections and will be handled as SAEs in the safety 
database (see the section on Serious Adverse Event Reporting Requirements).
8.6.2. Potential Cases of Drug-Induced Liver Injury 
Liver Function Tests (LFTs) are not required as a routine safety monitoring procedure in this 
study. However, should an investigator deem it necessary to run LFTs because of clinical 
sign/symptom presentation in a patient, such LFT results should be handled and followed up 
as described below. 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 112
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the patient’s individual baseline values and underlying conditions.  Patients who
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Patients with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (× ULN) concurrent with a total bilirubin value 2 × ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 × ULN or not available;

For patients with preexisting ALT OR AST OR total bilirubin values above the ULN, 
the following threshold values should be used in the definition mentioned above:

For patients with preexisting AST or ALT baseline values above the normal range:
AST or ALT value 2 times the baseline values and 3 × ULN, or 8 × ULN 
(whichever is smaller).
Concurrent with

For patients with pre-existing values of total bilirubin above the normal range: Total 
bilirubin level increased from baseline by an amount of at least 1 × ULN or if the 
value reaches 3 × ULN (whichever is smaller).
The patient should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered.  In addition to repeating 
measurements of AST and ALT, laboratory tests should include albumin, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time 
(PT)/international normalized ratio (INR), and alkaline phosphatase.  A detailed history, 
including relevant information, such as review of ethanol, acetaminophen, recreational drug, 
and supplement consumption, family history, occupational exposure, sexual history, travel 
history, history of contact with a jaundiced person, surgery, blood transfusion, history of liver 
or allergic disease, and work exposure, should be collected.  Further testing for acute 
hepatitis A, B, or C infection and liver imaging (eg, biliary tract) may be warranted.  All 
cases confirmed on repeat testing as meeting the laboratory criteria defined above, with no 
other cause for LFT abnormalities identified at the time, should be considered potential Hy’s 
law cases irrespective of availability of all the results of the investigations performed to 
determine etiology of the abnormal LFTs.  Such potential Hy’s law cases should be reported 
as SAEs.
8.7. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 113
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of persistent pre-treatment laboratory abnormality);

Social admission (eg, patient has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 114
8.8. Severity Assessment
GRADE
Clinical Description of Severity
0
No Change from normal or reference range (This grade is not included in the 
Version 4.03 CTCAE document but may be used in certain circumstances.)
1
MILD adverse event
2
MODERATE adverse event
3
SEVERE adverse event
4
LIFE-THREATENING consequences; urgent intervention indicated
5
DEATH RELATED TO adverse event
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example headache may be severe (interferes significantly with the 
patient’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs listed above.
8.9. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the sponsor (see the section on Reporting Requirements).  If the 
investigator's causality assessment is “unknown but not related to investigational product,”
this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures,
the investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.10. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 115
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant women (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male participant has been exposed (eg, because of treatment or environmental 
exposure) to the investigational product prior to or around the time of conception 
and/or is exposed during his partner’s pregnancy.
If a study patient or study patient’s partner becomes or is found to be pregnant during the 
study patient’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer drug safety unit on an SAE report form and an EDP supplemental 
form, regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
patient reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the EDP supplemental form.  This must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the exposure.  The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
the termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless preprocedure test 
findings are conclusive for a congenital anomaly and the findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the study patient with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 116
the patient was given the Pregnant Partner Release of Information Form to provide to his
partner.
8.11. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a patient enrolled in the study,
the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file.
8.12. Withdrawal Due to Adverse Events (See Also the Section on Patient Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.
When a patient withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.13. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study patient.  In addition, each study patient will be questioned about AEs.
8.14. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs,
expedited reporting will follow local and international regulations, as appropriate.
8.14.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.  In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be 
made immediately, irrespective of the extent of available AE information.  This time frame 
also applies to additional new information (follow-up) on previously forwarded SAE reports 
as well as to the initial and follow-up reporting of EDP, exposure via breastfeeding, and 
occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time
of his or her first awareness of the AE.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 117
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the time frames for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines, and/or illnesses, must be provided.  In the case of a patient death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.14.2. Non-Serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE 
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.
8.14.3. Medical Device Complaint Reporting Requirements
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be collected on the applicable pages within the CRF.  This 
includes potential incidents or malfunctions associated with the use of a medical device 
product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might have led to death or serious deterioration 
in health.
Significant medical device complaints are defined as those observations or incidences outside 
the expected normal operational ranges of the device (as detailed in the device specific 
training and instructions for use (IFU) documentation) that may have the potential to impact
the correct operation of the device, administration of the drug or safety of the patient.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event.  Complaints will be forwarded to the device manufacturer, Ichor 
Medical Systems (“Ichor”) (San Diego, CA) in accordance with the Quality Agreement 
between Pfizer and Ichor. 
8.14.4. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out
in accordance with applicable local regulations.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 118
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a statistical analysis plan (SAP), which will be maintained by the 
sponsor.  This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
9.1. Analysis Sets 
For safety evaluation, patients should have received at least one of the regimen components.  
For efficacy and pharmacodynamics evaluation, patients should have received at least one 
dose of all assigned components administered on Cycle 1 Day 1.  For example, a patient 
would be included in the safety analyses if he is assigned to a cohort of AdC68 6 x 1011 VP
in combination with tremelimumab but received only the AdC68 component.  However, this 
patient would not be included in the efficacy 
 evaluation for that cohort.  Patients who 
receive the designated investigational product of interest and have at least one post-dose drug 
concentration measurement will be included in the PK data analysis. Patients with major 
treatment deviations, defined as receiving <80% of their planned dose in the 28-day DLT 
observation period will not be evaluable for the MTD assessment and will be replaced as 
needed to permit MTD estimation.
1. Safety analysis set. 
The safety analysis set includes all enrolled patients who receive at least one dose of one of 
the components of the regimen. 
2. Full analysis set.
The full analysis set includes all enrolled patients.
3. Per protocol analysis set.
The per protocol (PP) analysis set includes all enrolled patients (for each indication) who 
receive at least one dose of all assigned regimen components administered on 
Cycle 1 Day 1 of study medication and who do not have major protocol deviations during the 
28 days after the first vaccination.
4. Modified Intention-to-Treat analysis set.
 
 
 
 
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 119
 
 
 
 
5. PK analysis set.
The PK parameter analysis population is defined as all enrolled patients treated who have
sufficient information to estimate at least 1 of the PK parameters of interest and who have no 
major protocol deviations influencing the PK assessment.
6. Immunogenicity analysis set.
The immunogenicity analysis set includes all enrolled patients who receive at least one dose 
of one of the components of the regimen.
9.2. Statistical Methods and Properties 
The dose escalation phase will be governed by three 3+3 designs, one for each regimen 
component.  The 3+3 design assumes that no more than 0 out of 3 (0/3) or 1 out of 6 (1/6) 
DLTs are observed at the highest tested dose level of a component and the highest dose is 
therefore taken forward for subsequent cohorts.  However, if a lower dose level for one 
component is determined to be the maximum tolerated dose, the lower level will be 
administered to subsequent cohorts. 
The following table shows the probability of escalating to the next dose level for a range of 
underlying true DLT rates.  For example, for a DLT that occurs in 10% of patients, there is a 
greater than 90% probability of escalating.  Conversely, for a DLT that occurs with a rate of 
70%, the probability of escalating is 3%. It is assumed that dose escalation occurs with either 
0/3 or 1/6 patients with DLTs.
Table 7.
Probability of Escalating Dose
True underlying DLT rate
10%
20%
30%
40%
50%
60%
70%
80%
90%
Probability of escalating
0.91
0.71
0.49
0.31
0.17
0.08
0.03
0.009
0.001
Probabilities of testing sequential doses can be calculated as the 3+3 escalation rules are 
predefined.  For example the probability of escalating to a third dose level is 0.64 under the 
assumption that DLTs occur in 10% and 20% of patients respectively in the first dose and the 
second dose.  The probability of escalating to a third dose is only 0.35 if DLTs occur in 
20% and 30% of patients respectively in the first dose and the second dose tested. 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 120
9.2.1. Dose Escalation
Enrollment of patients into dose escalation cohorts will occur in a sequential manner starting 
with the lowest dose level, and escalation being permitted following evaluation of acceptable 
safety data by the investigator and Sponsor according to the principles of the 3+3 design.  
Patients will be assigned to dose cohorts on the basis of their order of entry into the study.  
Dose cohorts with an acceptable safety profile (0/3 or 1/6 patients with DLTs) may be 
expanded up to N=15 to further assess safety.
There is an assumption that higher doses of either AdC68, tremelimumab or 
PF-06801591 result in higher adverse event rates.  However, due to the relatively low 
number of patients that may be potentially allocated to any dose combination, adverse event 
estimates may not follow this assumption and variable incidence of AEs can be observed. 
For example, the dose AdC68 4 x 1011VP in combination with tremelimumab 80 mg may 
have a higher proportion of observed adverse events than AdC68 4 x 1011VP in combination 
with tremelimumab 80 mg and PF-06801591 300 mg, and this variability may be simply 
related to small cohort size alone.  Clinical judgment will be exercised in taking forward 
combinations to the expansion cohort(s), in case no clear choice exists between more than 
1 competing dose regimen. 
9.3. Sample Size Determination
The exact sample size of the 3+3 designs in the Phase 1 Part A (Dose Escalation) cannot be 
pre-specified because of the dynamic feature of the design.  The number of patients to be 
enrolled in the study will depend upon the observed safety profile, which will determine the 
number of patients at each dose level (eg, 3 or 6) and the number of dose levels explored.
Typically, at least 3 patients will be treated at each regimen dose level.  Dose cohorts with an 
acceptable safety profile (0/3 or 1/6 patients with DLTs) may be expanded up to N=15 to 
further assess safety, immune response, pharmacokinetics, and pharmacodynamics.  
Decisions to enroll additional patients at dose levels already cleared for safety will be based 
on clinical judgment of the investigators and the sponsor considering all evaluable safety, 
immunoresponse, and/or pharmacodynamics data.
The estimated sample size for Part A would be 24-48 patients and will be dependent on the 
safety profile observed.
The sample size for Cohort 1B (AdC68 + pDNA + treme 80 mg SC for BCR patients who 
had no prior therapy) was determined clinically rather than statistically. Twenty patients 
were enrolled in that cohort to provide preliminary efficacy, safety, PK and biomarker data 
for this regimen. 
For Cohort 3B (AdC + pDNC + treme 80 mg SC + PF-0689159 300 mg SC. for patients with 
mCRPC whose disease has progressed despite novel hormonal treatment), 18 patients were 
enrolled. The sample size was determined clinically rather than statistically. The smaller 
sample size was determined to be adequate for continued safety analysis. The main efficacy 
endpoint for this cohort will be objective response rate (ORR) based on RECIST version 1.1.  
There are no hypothesis tests for these endpoints. Bayesian approach with a non-informative 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 121
Jeffery’s prior beta (0.5,0.5) will be used to calculate the posterior probability the ORR of the 
study treatment exceeds various ORR thresholds of interest in the end of the study. For 
example, if 6 responders were observed in the 18 patients, the posterior probability that the 
true ORR is greater than 25% would be about 80%.9
For Cohort 5B (AdC68 + pDNA + treme 80 mg SC + PF-0689159 130 mg SC. for BCR 
patients who had no prior therapy), the sample size was determined clinically rather than 
statistically. Fifteen patients were enrolled in that cohort to provide preliminary efficacy, 
safety, PK and biomarker data for the regimen. 
9.4. Efficacy Analysis
  The main 
analysis populations will be based on mITT and EP (see Section Analysis Sets).
Tumor response, using RECIST v1.1, irRECIST, and PCWG3 for bone disease, will be 
summarized and presented in the form of patient data listings.  Traditional response measures 
in solid tumors, such as ORR and PFS were developed to evaluate chemotherapies and can 
be unreliable for tracking response to cancer vaccines.  For example, apparent tumor burden 
may increase during the first few months of cancer vaccine treatment because of 
inflammation/T cell infiltration into tumors even in patients who go on to have durable 
responses.  For these reasons time to progression and number of patients with progression 
could be calculated from first vaccination (Day 1), but also calculated excluding those 
progressions that happened before some specific timepoints (eg, Day 57, Day 113).  Time to 
response will be calculated from first vaccination (Day 1) to time of first response (ie, CR or 
PR). When PFS is evaluated, the Kaplan-Meier approach will be used. Participants from 
Cohorts 7A and 3B may be combined for efficacy analyses as participants in those two 
cohorts have identical or similar eligibility criteria for study entry and are scheduled to 
receive the same regimen. 
Additionally, total measurable tumor burden will be evaluated by the irRECIST criteria that 
include responses after disease progression that are not captured by RECIST evaluation 
criteria in solid tumors. 
The Bayesian analyses as described in Section 9.3 will be carried out separately and may not 
be reported in the clinical study report. 
9.5. Safety Analysis
The main analyses of DLTs will be based on the Per Protocol analysis set.  Patients not 
meeting the criteria for inclusion in the Per Protocol Analysis set (ie, not evaluable for 
assessment of DLTs) will be replaced.  Summaries and analyses of other safety parameters 
will include all patients in the Safety Analysis Set (see Section Analysis Sets).
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 122
9.5.1. Analysis of Primary Endpoint
Dose Limiting Toxicity (DLT) is the primary endpoint of the dose escalation (Part A).  The 
occurrence of DLTs observed in the dosing cohorts will govern the dose escalation as 
described in Section 3.1.1 STUDY DESIGN.  The properties of the statistical methods for 
the analyses of DLTs are described in section Statistical Methods and Properties.  Adverse 
Events constituting DLTs will be listed per dose level. The per-protocol population will be 
used for the DLT evaluation. A patient who had a major protocol deviation may be excluded 
from the per-protocol population and hence will be replaced for the DLT evaluation but will 
still be included in the safety population for the general safety evaluation. 
Adverse Events (AEs) will be graded by the investigator according to the CTCAE 
version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA).  
The focus of AE summaries will be on Treatment-Emergent Adverse Events, those with 
initial onset or increasing in severity after the first dose of study treatment.  The number and 
percentage of patients who experienced any AE, SAE, treatment related AE, and treatment 
related SAE will be summarized according to worst toxicity grades.  The summaries will 
present AEs both on the entire study period by dose and by cycle. 
9.5.2. Analysis of Secondary Safety Endpoints
Laboratory Tests Abnormalities
The number and percentage of patients who experienced laboratory test abnormalities will be 
summarized according to worst toxicity grade observed for each lab assay.  The analyses will 
summarize laboratory tests both on the entire study period and by cycle (Cycle 1 and 
Cycles beyond 1). Shift tables will be provided to examine the distribution of laboratory 
toxicities.
For laboratory tests without CTCAE grade definitions, results will be categorized as normal,
abnormal or not done. 
9.5.3. ECG
The analysis of ECG results will be based on patients in the safety analysis set with baseline 
and on-treatment ECG data.  Baseline is defined as the pre-dose ECG collected before the 
first dose of any component of the study treatment.
ECG measurements (an average of the triplicate measurements) will be used for the 
statistical analysis and all data presentations.  Any data obtained from ECGs repeated for 
safety reasons after the nominal time-points will not be averaged along with the preceding 
triplicates.  Interval measurements from repeated ECGs will be included in the outlier 
analysis (categorical analysis) as individual values obtained at unscheduled time points.
QT intervals will be corrected for heart rate (QTc) using standard correction factors 
(ie, Frederica’s).  Data will be summarized and listed for QT, HR, PR, QRS, QTcF by cohort.  
Individual QT intervals will be listed by time and cohort.  Descriptive statistics (n, mean, 
median, standard deviation, minimum, and maximum) will be used to summarize the 
absolute corrected QT interval and changes from baseline in corrected QT after treatment by 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 123
cohort and time point.  For each patient and by treatment, the maximum change from 
baseline will be calculated as well as the maximum post-baseline interval across time-points. 
Categorical analysis will be conducted for the maximum change from baseline in corrected 
QT and the maximum post-baseline QT interval. 
Shift tables will be provided for baseline vs worst on treatment corrected QT using 
Maximum CTC AE Grade.  Shift tables will also be provided for ECG abnormality at 
baseline vs. on treatment (yes, no, not done: (n, %)).  Patients experiencing 
clinically-relevant morphological ECG changes will be summarized (including frequency 
and percentage).
If applicable, the effect of relevant drug concentrations on corrected QT change from 
baseline will be explored graphically.  Additional concentration-corrected QT analyses may 
be performed.  Data may be pooled with other study results and/or explored further with 
PK/PD models.
9.6. Analysis of Other Endpoints
9.6.1. Pharmacokinetic Analyses
9.6.1.1. Tremelimumab Pharmacokinetics
The concentration-time data of tremelimumab will be summarized by descriptive statistics 
(n, mean, standard deviation, median, minimum, and maximum) according to dosing cohort 
and time.
For patients of Cohort 3A, the concentration-time data of tremelimumab after the first dose 
will be analyzed individually by non-compartmental methods to determine the PK 
parameters.  The PK parameters to be estimated will include the Cmax, Tmax, AUClast, and if 
data permit, AUCinf, terminal elimination half-life (t1/2), and apparent clearance (CL/F).  In 
addition, the accumulation ratio (Rac) as calculated by the ratio of the trough concentration 
prior to the fifth tremelimumab dose (on Cycle 2 Day 1) to the concentration prior to the 
second tremelimumab dose (on Cycle 1, Day 29) will be determined individually if data 
permit.  The PK parameters will be summarized using descriptive statistics according to
dosing cohort.
9.6.1.2. PF-06801591 Pharmacokinetics
The concentration time data of PF-06801591 will be summarized by descriptive statistics (n, 
mean, standard deviation, median, minimum, and maximum) according to dosing cohort and 
time.
For patients of Cohorts 6A through 9A, the concentration time data of PF-06801591 after the 
first dose will be analyzed individually by non-compartmental methods to determine the PK 
parameters.  The PK parameters to be estimated will include the Cmax, Tmax, and AUClast, and 
if data permit, AUCinf, t1/2, and CL/F.  In addition, Rac as calculated by the ratio of the trough 
concentration prior to the fifth PF-06801591 dose (on Cycle 2 Day 1) to the concentration 
prior to the second PF-06801591 dose (on Cycle 1, Day 29) will be determined individually 
if data permit.  The PK parameters will be summarized using descriptive statistics according 
to dosing cohort.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 124
9.6.2. Immune Responses and Tremelimumab Immunogenicity
The time course data on immune response endpoints, including titers of antibodies against 
prostate cancer specific antigens and titers of antigen-specific T cells, will be summarized by 
descriptive statistics (n, median, minimum, and maximum) according to dosing cohort and 
time.  If data permit, the time course data may also be analyzed by non-compartmental 
methods to estimate parameters including peak titers, time to peak titers, and area under the 
titer curve. 
For patients receiving tremelimumab, the percentage of patients with positive ADA and 
neutralizing antibodies will be summarized by dosing cohort.  For patients with positive 
ADA, the magnitude (titer), time of onset, and duration of ADA response will also be 
described, if data permit.
For patients receiving PF-06801591, the percentage of patients with positive ADA and 
neutralizing antibodies will be summarized by dosing cohort.  For patients with positive 
ADA, the magnitude (titer), time of onset, and duration of ADA response will also be 
described, if data permit.
 
 
 
 
 
 
 
 
 
 
 
  
 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 125
 
9.7. Data Safety Monitoring Committee 
An external Data Safety Monitoring Committee will not be established for the study.  For the 
purpose of this protocol, Pfizer procedures for periodic safety review will be applied by an 
internal safety review team with medical and statistical capabilities to review individual and 
summary data collected in the safety and clinical databases.  Procedures include:
Surveillance for serious adverse events (SAEs) according to regulatory guidelines.
Discussions between the investigators and the sponsor of AEs and laboratory tests alterations 
seen at each dose level in an on-going manner at regular teleconferences and/or meetings to 
determine the safety profile and risk/benefit ratio and decide if further enrollment is 
appropriate.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
During study conduct and/or after study completion, the study site may be subject to review 
by the institutional review board (IRB)/ethics committee (EC), and/or to quality assurance 
audits performed by Pfizer, or companies working with or on behalf of Pfizer, and/or to 
inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the study site for the inspection and will allow Pfizer or its agent, 
whenever feasible, to be present during the inspection.  The investigator will promptly 
provide copies of the inspection findings to Pfizer or its agent.  Before response submission 
to the regulatory authorities, the investigator will provide Pfizer or its agents with an 
opportunity to review and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 126
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included patient.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed,  and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital's or the physician's patient chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigative site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating patients (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to ICH guidelines, according to local regulations, or 
as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 127
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board (IRB)/Ethics Committee (EC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the patients.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
12.3. Patient Information and Consent
All parties will ensure protection of patient personal data and will not include patient names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, patient 
names, addresses, and other identifiable data will be replaced by a numerical code consisting 
of a numbering system provided by Pfizer in order to de-identify study patients.  The study 
site will maintain a confidential list of patients who participated in the study, linking each 
patient’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of patients’ personal data consistent 
with applicable privacy laws.
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed and approved by the sponsor, approved by the IRB/EC before use, and available for 
inspection.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 128
The investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient before any study-specific activity is performed.  The investigator 
will retain the original of each patient's signed consent document.
12.4. Patient Recruitment
Advertisements approved by IRBs/ECs and investigator databases may be used as 
recruitment procedures.
Pfizer will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study patients before such materials are used.
12.5. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study patients against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
End of trial is defined as last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
In the event of a Grade 4 or Grade 5 AE of Special Interest (meeting criteria for serious),
such as cardiac or neurologic toxicity, enrollment and dosing in the study will pause, to allow 
for a thorough internal safety evaluation, possible external safety analysis and 
recommendations, and communication with the FDA. Enrollment and dosing will begin in 
the study only after agreement with the FDA.
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, investigational product problems, or at the discretion of 
Pfizer.  In addition, Pfizer retains the right to discontinue development of PrCa VBIR at any 
time.If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating patients and 
the hospital pharmacy (if applicable) within a time period set by Pfizer.  As directed by 
Pfizer, all study materials must be collected and all CRFs completed to the greatest extent 
possible.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 129
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date for 
studies in adult populations or within 6 months of the primary completion date for studies in 
pediatric populations.
Primary completion date is defined as the date that the final patient was examined or received 
an intervention for the purposes of final collection of data for the primary outcome, whether 
the clinical study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts EU Basic Results on EudraCT for all Pfizer-sponsored interventional studies that 
are in scope of EU requirements.  EU Basic Results are submitted for posting within 1 year 
of the primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product.  
However, to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “Publication”) 
before it is submitted or otherwise disclosed.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 130
The investigator will provide any publication to Pfizer at least 30 days before they are 
submitted for publication or otherwise disclosed.  If any patent action is required to protect 
intellectual property rights, the investigator agrees to delay the disclosure for a period not to 
exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all study sites, and that any subsequent publications by the 
principal investigator will reference that primary publication.  However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
study at all participating sites, the investigator is free to publish separately, subject to the
other requirements of this section.
For all publications relating to the study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study patients, and the CSA will control as to all other 
issues.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 131
16. REFERENCES
1.
Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and 
abiraterone in prostate cancer. N Engl J Med 2014 Sep 11;371(11):1028-38.
2.
Beer TM, Armstrong AF, Rathkopf DE, et al.  Enzalutamide in Metastatic Prostate 
Cancer before Chemotherapy.  N Engl J Med 2014:371;424 33.
3.
Bishop, JL, Sio, A, Angeles, A, et al. PD-LA is highly expressed in enzalutamide 
resistant prostate cancer. Oncotarget 2015;6:234-242.
4.
Camacho LH, Antonia S, Sosman J, et al.  Phase I/II trial of tremelimumab in patients 
with metastatic melanoma.  J Clin Oncol.  2009;27(7):1075-81.
5.
Casimiro, D.R., et al., Comparative immunogenicity in rhesus monkeys of DNA 
plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors 
expressing a human immunodeficiency virus type 1 gag gene. J Virol, 2003. 77(11): 
p. 6305-13.
6.
Chirmule N, Propert K, Magosin S, Qian Y, Qian R, Wilson J. 1999. Immune responses 
to adenovirus and adeno-associated virus in humans. Gene Ther 6: 1574-83.
7.
Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI. 2007. 
Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial 
carcinoma.  The American Journal of Surgical Pathology 31: 1246-55.
8.
Conteduca V, Aieta M, Amadori D, De Giorgi U. Neuroendocrine differentiation in 
prostate cancer: current and emerging therapy strategies. Crit Rev Oncol Hematol. 2014
Oct;92(1):11-24.
9.
De Bono JS, Chowdhury S, Feyerabend S, et al. Antitumor activity and safety of 
enzalutamide in patients with metastatic castration-resistand prostate cancer previously 
treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe. European 
Urology 74 (2018): 37-45.
10.
Dykstra R, Robertson T. An algorithm for isotonic regression for two or more 
independent variables. Ann Stat. 1982;10:708-716.
11.
Efstathiou E, Titus M, Wen S, et al. Molecular characterization of enzalutamide-treated 
bone metastatic castration-resistant prostate cancer. Eur Urol. 2015 Jan;67(1):53-60.
12.
Ersching J, Hernandez MI, Cezarotto FS, Ferreira JD, Martins AB, et al. 2010. 
Neutralizing antibodies to human and simian adenoviruses in humans and New-World 
monkeys. Virology 407: 1-6.
13.
Ford TF, Butcher DN, Masters JR, Parkinson MC. 1985. Immunocytochemical 
localisation of prostate-specific antigen: specificity and application to clinical practice. 
British journal of urology 57: 50-5.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 132
14.
Graff JN et al. Pembrolizumab plus enzalutamide in metastatic castration resistant 
prostate cancer: extended follow up. [2018 ASCO Genito-Urinary Meeting]. J Clin 
Oncol 36, no 15_suppl (May 20, 2018) 5047. 
15.
Gu Z, Thomas G, Yamashiro J, Shintaku IP, Dorey F, et al. 2000. Prostate stem cell 
antigen (PSCA) expression increases with high gleason score, advanced stage and bone 
metastasis in prostate cancer. Oncogene 19: 1288-96.
16.
Haas NB, Manola J, Ky B, et al.  Cardiac safety analysis for a phase III trial of sunitinib 
(SU) or sorafenib (SO) or placebo (PLC) in patients (pts) with resected renal cell 
carcinoma (RCC).  J Clin Oncol.  2012;30(15)(Suppl):Abstr 4500.
17.
Halabi, S., et al., Prognostic model for predicting survival in men with 
hormone-refractory metastatic prostate cancer. J Clin Oncol, 2003. 21(7): p. 1232-7.
18.
Hodi FS, O’Day SJ, McDermott DF, et al.  Improved survival with ipilimumab in 
patients with metastatic melanoma.  N Engl J Med.  2010;363(8):711-23.
19.
Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-
resistant prostate cancer. N Engl J Med.  2018;378(26):2465-74.  
20.
Jochems C, Tucker JA, Tsang KY, Madan RA, Dahut WL, et al. 2014.  A combination 
trial vaccine plus ipilumamab in metastatic castration-resistant prostate cancer patients: 
immune correlates. Cancer Immunol Immunother 63: 407-18.
21.
Kantoff PW, Schuetz TJ, Blumenstein BA, et al.  Overall survival analysis of a phase II 
randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in 
metastatic castration-resistant prostate cancer.  J Clin Oncol.  2010;28(7):1099-105.
22.
Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, et al. 2009.  Sunitinib mediates reversal of 
myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clinical 
Cancer Research 15: 2148-57.
23.
Lam, J.S., Yamashiro J, Shintaku IP, Vessella RL, Jenkins RB, et al., Prostate stem cell 
antigen is overexpressed in prostate cancer metastases. Clin Cancer Res, 2005. 11(7): 
p. 2591-6.
24.
Lesokhin, A.M., T. Merghoub, and J.D. Wolchok, Myeloid-derived suppressor sells and 
the efficacy of CD8 T cell immunotherapy. Oncoimmunology, 2013. 2(2): p. e22764.
25.
Loeb S, Metter EJ, Kan D, Roehl KA, Catalona WJ. 2012. Prostate-specific antigen 
velocity (PSAV) risk count improves the specificity of screening for clinically 
significant prostate cancer. BJU Int 109: 508-13; sicussion 13-4.
26.
Loeb S, Sutherland DE, D’Amico AV, Roehl KA, Catalona WJ. 2008. PSA velocity is 
associated with gleason score in radical prostatectomy specimen: marker for prostate 
cancer aggressiveness. Urology 72: 1116-20; discussion 20.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 133
27.
Madan RA, Gulley JL, Schlom J, et al. Analysis of Overall Survival in Patients with 
Nonmetastatic Castration-Resistant Prostate Cancer Treated with Vaccine, Nilutamide, 
and Combination Therapy. Clin Cancer Res 2008; 14(14):4526-31.
28.
Mast TC, Kierstead L, Gupta SB, Nikas AA, Kallas EG, et al. 2010. International 
epidemiology of human pre-existing adenovirus (Ad) type-5, type-6, type-26 and 
type-36 neutralizing antibodies: correlates of high Ad5 titers and implications for 
potential HIV vaccine trials. Vaccine 28: 950-7.
29.
Minner S, Wittmer C, Graefen M, Salomon G, Steuber T, et al. 2011. High level PSMA
expression is associated with early PSA recurrence in surgically treated prostate cancer. 
Prostate 71: 281-8.
30.
Madan, R.A., et al., Ipilimumab and a poxviral vaccine targeting prostate-specific 
antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. 
Lancet Oncol, 2012. 13(5): p. 501-8.
31.
Morse MA, Chaudhry A, Gabitzsch ES, et al.  Novel adenoviral vector induces T cell 
responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.  
Cancer Immunol Immunother.  2013;62(8):1293–301.
32.
Nishino M et al. Developing a common language for tumor response to immunotherapy: 
immune-related response criteria using unidimensional measurements. Clin Cancer Res. 
2013 Jul 15;19(14):3936-43.
33.
Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS. Optimizing immune-related 
tumor response assessment: does reducing the number of lesions impact response 
assessment in melanoma patients treated with ipilimumab?  J Immunother Cancer  
2014;2:17.
34.
Nunes FA, Furth EE, Wilson JM, et al.  Gene transfer into the liver of nonhuman 
primates with E1-deleted recombinant adenoviral vectors: safety of readministration.  
Hum Gene Ther. 1999;10(15);2515–26.
35.
Perner S, Hofer MD, Kim R, Shah RB, Li H, et al. 2007.  Prostate-specific membrane 
antigen expression as a predictor of prostate cancer progression. Human pathology 38: 
696-701.
36.
Porter, DL, et al., Chimeric antigen receptor-modified T cells in chronic lymphoid 
leukemia. N Engl J Med, 2011. 365(8): p. 725-33.
37.
Prostate Cancer: what are the key statistics about prostate cancer? American Cancer 
Society. Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014.
38.
Raper SE, Chirmule N, Lee FS, et al.  Fatal systemic inflammatory response syndrome 
in a ornithine transcarbamylase deficient patient following adenoviral gene transfer.  
Mol Genet Metabol. 2003;80(1-2):148–58.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 134
39.
Raper SE, Haskal ZJ, Ye X, et al.  Selective gene transfer into the liver of nonhuman 
primates with E1-deleted, E2A-defective, or E1–E4 deleted recombinant adenoviruses.  
Hum Gene Ther.  1998;9:671–9.
40.
Raper SE, Yudkoff M, Chirmule N, et al.  A pilot study of in vivo liver-directed gene 
transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency.  
Hum Gene Ther.  2002;13(1):163-75.
41.
Ribas A, Kefford R, Marshall MA, et al.  Phase III randomized clinical trial comparing 
tremelimumab with standard-of-care chemotherapy in patients with advanced 
melanoma.  Clin Oncol.  2013;31(5):616-22.
42.
Rini BI, Stein M, Shannon P, et al.  Phase 1 dose-escalation trial of tremelimumab plus 
sunitinib in patients with metastatic renal cell carcinoma.  Cancer.  2011;117(4):758-67.
43.
Ryan CJ, Smith MR, Fizazi K et al. Abiraterone acetate plus prednisone versus placebo 
plus prednisone in chemotherapy-naïve men with metastatic castration-resistant prostate 
cancer (COU-AA-302): final overall survival analysis of a randomized, double-blind, 
placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60.
44.
Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate 
cancer after chemotherapy. N Engl J Med 2012;367:1187-97.
45.
Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-
Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer 
Clinical Trials Working Group 3.  Journal of Clinical Oncology 2016 34:12, 1402-1418.
46.
Schroder FH, Kranse R, Barbet N, et al. Prostate-Specific Antigen: A Surrogate 
Endpoint for Screening New Agents Against Prostate Cancer? The Prostate 42:107–115 
(2000).
47.
Sharma P, Pachynski R, Narayan V, et al. Initial results from a Phase 2 Study of 
nivolumab plus ipilimumab for the treatment of metastatic castration-resistant prostate 
cancer (CheckMate 650). [2019 ASCO Genito-Urinary Meeting]. J Clin Oncol 37, no 
7_suppl (March 1, 2019) 1-1.
48.
Smith MR and Kantoff PW, Changes in PSA kinetics after DNA vaccine therapy-not so
fast! J Clin Oncol, 2010. 28(4):p. e58; author reply e59.
49.
Sweat, S.D., et al., Prostate-specific membrane antigen expression is greatest in prostate 
adenocarcinoma and lymph node metastases. Urology, 1998. 52(4): p. 637-40.
50.
Tatsis N, Ertl HC. 2004. Advenovirus as vaccine vectors. Molecular therpay: the journal 
of the American Society of Gene Therapy 10: 616-29.
51.
Topalian SL, Hodi FS, Brahmer JR, et al.  Safety, activity, and immune correlates of 
anti-PD-1 antibody in cancer.  N Engl J Med.  2012;366(26):2443-54.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 135
52.
van Cruijsen H, van der Veldt AA, Vroling L, Oosterhoff D, Broxterman HJ, et al. 
2008. Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: 
CD1c+ dendritic cell frequency predicts progression-free survival. Clinical cancer 
research : an official journal of the American Association for Cancer Research 14: 
5884-92.
53.
van den Eertwegh, A.J., et al., Combined immunotherapy with granulocyte-macrophage 
colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in 
patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation 
trial. Lancet Oncol, 2012. 13(5): p. 509-17.
54.
Vuk-Pavlovic, S., et al., Immunosuppressive CD14+HLA-DRlow/- monocytes in 
prostate cancer. Prostate, 2010. 70(4): p. 443-55.
55.
XTANDI® United States Prescribing Information 7/2018. Astellas Pharma US, Inc., 
Northbrook, IL 60062; Pfizer Inc., New York, NY 10017. 
https://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf
56.
Ye X, Gao GP, Pabin C, et al.  Evaluating the potential of germ line transmission after 
intravenous administration of recombinant adenovirus in the C3H mouse.  Hum Gene 
Ther.  1998;9(14):2135–42.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 136
Appendix 1. Abbreviations
This is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AChR
Acetylcholine receptor
ADA
Anti-drug Antibody
ADT
Androgen Deprivation Therapy
AdC68
Adenovirus C68
ADR
Adverse Drug Reaction
AE
Adverse Event
ALK
Anaplastic Lymphoma Kinase
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
AUC
Area Under the Concentration-Time Curve
AUCtau
Area Under the Serum Concentration-time Curve Over the 
Dosing Interval
BP
Blood Pressure
BCR
Biochemical Relapse
CBC
Complete Blood Count
CD
Cluster of Differentiation
CI
Confidence Interval
CL/F
Apparent Clearance
CLss/F
Clearance at steady state
Cmax
Maximum Drug Concentration
CR
Complete Response
CRF
Case Report Form
CRPC
Castrate Resistant Prostate Cancer
CT
Computed Tomography
CTLA4
Anti-cytotoxic T Lymphocyte-associated antigen 4
cTnI
Cardiac troponin I
Ctrough
Trough Concentrations after Multiple Dosing
CYP450
Cytochrome P450 enzymes
DLT
Dose Limiting Toxicities
DMSO
Dimethyl-sulfoxide
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
EGFR
Epidermal Growth Factor Receptor
FDA
Food and Drug Administration
FoxP3
Forkhead box P3
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 137
Abbreviation
Term
GCP
Good Clinical Practice
GGT
Gamma-glutamyltransferase
GnRh
Gonadotropin-releasing Hormone
HIV
Human Immunodeficiency Virus
HR
Hazard Ratio
IB
Investigator’s Brochure
ICAM-1
Intercellular Adhesion Molecule-1
ICOS
Inducible T-cell costimulator
IgG4
Immunoglobulin type G4
IHC
Immunohistochemistry
IFN
Interferon
IM
Intramuscular
IND
Investigational New Drug
INR
International Normalized Ratio
IP
Investigational Product
irRECIST
Immune-Related Response Evaluation Criteria in Solid Tumors
IV
Intravenous
LAG3
Lymphocyte activation gene 3
LFA-3
Lymphocyte Function-Associated Antigen 3
MAb
Monoclonal antibody
MDSC
Myeloid Derived Suppressor Cell
mCRPC
Metastatic Castrate Resistant Prostate Cancer
MHC
Major Histocompatibility Complex
MFD
Maximum Feasible Dose
MFS
Metastasis-free Survival
MG
Myasthenia gravis
mTPI
Modified Toxicity Probability Interval
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
MUGA
Multigated Acquisition Scan
MVA
Modified Vaccinia Virus Ankara
Nab
Neutralizing antibody
NHP
Non-Human Primates
NCI CTCAE
National Cancer Institute Common Terminology Criteria for 
Adverse Events
NOAC
New oral anticoagulant
NSCLC
Non-Small Cell Lung Cancer
ORR
Objective Response Rate
OS
Overall Survival
PBMC
Peripheral Blood Mononuclear Cell
PCWG3
Prostrate Cancer Working Group 3
CCI
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 138
Abbreviation
Term
PD-1
Programmed cell death protein-1
PD-L1
Programmed death-ligand 1
PD-L2
Programmed death-ligand 2
pDNA
Plasmid DNA
PFS
Progression Free Survival
PK
Pharmacokinetics
PR
Partial Response
PrCa
Prostate Cancer 
PSA
Prostate Specific Antigen
PSADT
Prostate Specific Antigen Doubling Time
PSCA
Prostate Stem Cell Antigen
PSMA
Prostate-Specific Membrane Antigen
PT
Prothrombin Time
PTT
Partial Thromboplastin Time
Q3W
Every 3 Weeks
Q4W
Every 3 Weeks
QoL
Quality of Life
Rac
Accumulation ratio
RECIST
Response Evaluation Criteria in Solid Tumors
RP2D
Recommended Phase 2 Dose
rPFS
Radiographic Progression-free Survival
SAE
Serious Adverse Event
SARS-CoV2
Severe Acute Respiratory Syndrome CoronaVirus 2
SC
Subcutaneous
SOA
Schedule of Assessments
SRE
Skeletal Related Event
SRSD
Single Reference Safety Document
t1/2
Half-life
TCR
T cell receptor
TEAEs
Treatment Emergent Adverse Events
Tmax
Time to Maximum Concentration 
TDS-IM
TriGrid Delivery System 
TTPP
Time to PSA progression
UTN
Universal trial number
VBIR
Vaccine-based immunotherapy regimen
Vd/F
Apparent Volume of Distribution
VP
Virus Particles
WBC
White Blood Cell
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 139
Appendix 2. ECOG Performance Status
Grade
ECOG Performance Status
0
Fully active, able to carry on all pre-disease performance without restriction.
1
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, 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.
*As published in Am J Clin Oncol 5:649 655, 1982.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 140
Appendix 3. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines
Adapted from E.A. Eisenhauer, et al: New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1).  European Journal of Cancer 45 (2009) 228–247. 
CATEGORIZING LESIONS AT BASELINE
Measurable Lesions
Lesions that can be accurately measured in at least one dimension.

Lesions with longest diameter twice the slice thickness and at least 10 mm or greater 
when assessed by CT or MRI (slice thickness 5-8 mm).

Lesions with longest diameter at least 20 mm when assessed by Chest X-ray. 

Superficial lesions with longest diameter 10 mm or greater when assessed by caliper.

Malignant lymph nodes with the short axis 15 mm or greater when assessed by CT.
NOTE: The shortest axis is used as the diameter for malignant lymph nodes, longest 
axis for all other measurable lesions. 
Non-measurable disease 
Non-measurable disease includes lesions too small to be considered measurable (including 
nodes with short axis between 10 and 14.9 mm) and truly non-measurable disease such as
pleural or pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, 
lymphangitic involvement of skin or lung, clinical lesions that cannot be accurately measured 
with calipers, abdominal masses identified by physical exam that are not measurable by 
reproducible imaging techniques.

Bone disease (based on PCWG3 criteria): Bone disease is defined as present or absent 
and will be followed as non-target lesions.

Previous local treatment: A previously irradiated lesion (or lesion patiented to other 
local treatment) is non-measurable unless it has progressed since completion of 
treatment.
Normal sites

Cystic lesions: Simple cysts should not be considered as malignant lesions and should 
not be recorded either as target or non-target disease.  Cystic lesions thought to 
represent cystic metastases can be measurable lesions, if they meet the specific 
definition above.  If non-cystic lesions are also present, these are preferred as target
lesions.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 141

Normal nodes: Nodes with short axis <10 mm are considered normal and should not 
be recorded or followed either as measurable or non-measurable disease.
Recording Tumor Assessments 
All sites of disease must be assessed at baseline.  Baseline assessments should be done as 
close as possible prior to study start.  For an adequate baseline assessment, all required scans 
must be done within 28 days prior to treatment and all disease must be documented 
appropriately.  If baseline assessment is inadequate, subsequent statuses generally should be 
indeterminate. 
Target lesions
All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total, 
representative of all involved organs, should be identified as target lesions at baseline.  
Target lesions should be selected on the basis of size (longest lesions) and suitability for 
accurate repeated measurements.  Record the longest diameter for each lesion, except in the 
case of pathological lymph nodes for which the short axis should be recorded. The sum of 
the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions 
at baseline will be the basis for comparison to assessments performed on study. 

If two target lesions coalesce the measurement of the coalesced mass is used.  If a 
large target lesion splits, the sum of the parts is used.

Measurements for target lesions that become small should continue to be recorded.  If 
a target lesion becomes too small to measure, 0 mm should be recorded if the lesion is 
considered to have disappeared; otherwise a default value of 5 mm should be 
recorded.
NOTE: When nodal lesions decrease to <10 mm (normal), the actual measurement 
should still be recorded.
Non-target disease 
All non-measurable disease is non-target.  All measurable lesions not identified as target 
lesions are also included as non-target disease.  Measurements are not required but rather 
assessments will be expressed as ABSENT, INDETERMINATE, PRESENT/NOT 
INCREASED, INCREASED.  Multiple non-target lesions in one organ may be recorded as a 
single item on the case report form (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple 
liver metastases’).
OBJECTIVE RESPONSE STATUS AT EACH EVALUATION
Disease sites must be assessed using the same technique as baseline, including consistent 
administration of contrast and timing of scanning.  If a change needs to be made the case 
must be discussed with the radiologist to determine if substitution is possible.  If not, 
subsequent objective statuses are indeterminate. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 142
Target disease
•
Complete Response (CR): Complete disappearance of all target lesions with the 
exception of nodal disease.  All target nodes must decrease to normal size (short axis 
<10 mm).  All target lesions must be assessed.
•
Partial Response (PR): Greater than or equal to 30% decrease under baseline of the 
sum of diameters of all target measurable lesions.  The short diameter is used in the 
sum for target nodes, while the longest diameter is used in the sum for all other target 
lesions.  All target lesions must be assessed. 
•
Stable: Does not qualify for CR, PR or Progression.  All target lesions must be 
assessed.  Stable can follow PR only in the rare case that the sum increases by less 
than 20% from the nadir, but enough that a previously documented 30% decrease no 
longer holds. 
 
•
Indeterminate.  Progression has not been documented, and 
•
One or more target measurable lesions have not been assessed; 
•
Or assessment methods used were inconsistent with those used at baseline;
•
Or one or more target lesions cannot be measured accurately (eg, poorly visible
unless due to being too small to measure);
•
Or one or more target lesions were excised or irradiated and have not reappeared 
or increased. 
Non-target disease
•
CR: Disappearance of all non-target lesions and normalization of tumor marker
levels.  All lymph nodes must be ‘normal’ in size (<10 mm short axis).
•
Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level 
above the normal limits. 
•
PD: Unequivocal progression of pre-existing lesions.  Generally the overall tumor 
burden must increase sufficiently to merit discontinuation of therapy.  In the presence 
of SD or PR in target disease, progression due to unequivocal increase in non-target 
disease should be rare. 
CCI

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 143

Indeterminate: Progression has not been determined and one or more non-target sites 
were not assessed or assessment methods were inconsistent with those used at 
baseline.
New Lesions 
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example due to its small size, continued assessment will clarify the etiology.  
If repeat assessments confirm the lesion, then progression should be recorded on the date of 
the initial assessment.  A lesion identified in an area not previously scanned will be
considered a new lesion.
Supplemental Investigations

If CR determination depends on a residual lesion that decreased in size but did not 
disappear completely, it is recommended the residual lesion be investigated with 
biopsy or fine needle aspirate.  If no disease is identified, objective status is CR.

If progression determination depends on a lesion with an increase possibly due to 
necrosis, the lesion may be investigated with biopsy or fine needle aspirate to clarify 
status. 
Subjective progression
Patients requiring discontinuation of treatment without objective evidence of disease 
progression should not be reported as PD on tumor assessment CRFs.  This should be 
indicated on the end of treatment CRF as off treatment due to Global Deterioration of Health
Status.  Every effort should be made to document objective progression even after 
discontinuation of treatment. 
Table 1. Objective Response Status at each Evaluation
Target Lesions
Non-target Disease
New Lesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD
No
PR
CR
Indeterminate or Missing
No
PR
PR
Non-CR/Non-PD, 
Indeterminate, or Missing
No
PR
SD
Non-CR/Non-PD, 
Indeterminate, or Missing
No
Stable
Indeterminate or 
Missing
Non-PD
No
Indeterminate
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 144
Table 2. Objective Response Status at each Evaluation for Patients with Non-Target Disease Only
Non-target Disease
New Lesions
Objective status
CR
No
CR
Non-CR/Non-PD
No
Non-CR/Non-PD
Indeterminate
No
Indeterminate
Unequivocal progression
Yes or No
PD
Any
Yes
PD

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 145
Appendix 4. Immune-Related Response Criteria Derived from RECIST 1.1 (irRECIST)
Increasing clinical experience indicates that traditional response criteria may not be sufficient 
to fully characterize activity in this new era of targeted therapies and/or biologics. 
This is particularly true for immunotherapeutic agents such as anti-CTLA4 and 
anti-PD-1/anti-PD-L1 antibodies which exert the antitumor activity by augmenting activation 
and proliferation of T cells, thus leading to tumor infiltration by T cells and tumor regression 
rather than direct cytotoxic effects.1,2 Clinical observations of patients with advanced 
melanoma treated with ipilimumab, for example, suggested that conventional response 
assessment criteria such as Response Evaluation Criteria in Solid Tumors (RECIST) and 
WHO criteria are not sufficient to fully characterize patterns of tumor response to 
immunotherapy because tumors treated with immunotherapeutic agents may show additional 
response patterns that are not described in these conventional criteria.3,4
Furthermore, the conventional tumor assessment criteria (RECIST and WHO criteria) have 
been reported as not capturing the existence of a subset of patients who have an OS similar to 
those who have experienced CR or PR but were flagged as PD by WHO criteria.3,4
On these grounds, a tumor assessment system has been developed that incorporates these 
delayed or flare-type responses into the RECIST v1.1 (irRECIST).5
For irRECIST, only target and measurable lesions are taken into account.  In contrast to 
RECIST v1.1, irRECIST: 

Requires confirmation of progression by imaging at least 4 weeks from the date first 
documented, and 

Does not necessarily score the appearance of new lesions as progressive disease if the 
sum of lesion diameters of target lesions (minimum of 10 mm longest diameter per 
non-nodal lesion and 15 mm shortest diameter per nodal lesion, maximum of 5 target 
lesions, maximum of 2 per organ) and measurable new lesions does not increase by 
20%. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported target lesion(s) at baseline and throughout the trial. 
irRECIST is defined as follows: 

Overall immune-related complete response (irCR): Complete disappearance of all 
lesions (whether measurable or not) and no new lesions.  All measurable lymph nodes 
also must have a reduction in short axis to <10 mm. 

Overall immune-related partial response (irPR): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions 
decreases 30%. 

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 146

Overall immune-related stable disease (irSD): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions is 
neither irCR, irPR, (compared to baseline) or immune-related progressive disease 
(irPD, compared to nadir). 

Overall immune-related progressive disease (irPD): Sum of the diameters (longest for 
non-nodal lesions, shortest for nodal lesions) of target and new measurable lesions 
increases 20% (compared to nadir), confirmed by a repeat, consecutive observation 
at least 4 weeks from the date first documented. 
New measurable lesions: Incorporated into tumor burden (ie, added to the target lesion 
measurements). A lymph node has to be 15 mm in short axis to be a measurable new lesion 
and its short axis measurement is included in the sum. Up to 2 new lesions per organ and up 
to 5 new lesions in total can be added to the measurements. 
New non-measurable lesions: Do not define progression but preclude irCR.
Overall responses derived from changes in index, non-index, and new lesions are outlines in
Table 8.
Table 8.
Overall Response Derived from Changes in Index, Non-index and New 
Lesions
Measurable response
Non-measurable Response
Overall response using 
irRECISTb
Index and New 
Measurable Lesions 
(Tumor Burden)a
Non-Index Lesions
New Non-Measurable 
Lesions
Decrease 100%
Absent
Absent
irCR
Decrease 100%
Stable
Any
irPR
Decrease 100%
Unequivocal progression
Any
irPR
Decrease 30%
Absent/stable
Any
irPR
Decrease 30%
Unequivocal progression
Any
irPR
Decrease <30% and 
increase <20%
Absent/stable
Any
irSD
Decrease <30% and 
increase <20%
Unequivocal progression
Any
irSD
Increase 20%
Any
Any
irPD
a.
Decrease assessed relative to baseline.
b.
Response (irCR and irPR) and progression (irPD) must be confirmed by a second, consecutive 
assessment at least 4 weeks apart.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 147
References:
1. Hoos A, Egermont AM, Janetzki S, et al. Improved endpoints for cancer immunotherapy 
trials.  J Natl Cancer Inst  2010;102(18):1388-1397.
2. Hodi FS, Bulter M, Oble DA, Seiden MV, haluska FG, Kruse A, et al. Immnologic and 
clinical effects of antibody blockade of cytotoic T lymphocyte-associated antigen 4 in 
previously vaccinated cancer patients.  Proc Natl Acad Sci U S A  2008;105:3005-3010.
3. Wolchok JD, et al.: Guidelines for the Evaluation of Immune Therapy Activity in Solid 
Tumors: Immune-Related Response Criteria.  Clin Cancer Res  2009;15(23):7412-7420.
4. Nishino M, Jagannathan JP, Krajewski KM, O'Regan K, Hatabu H, Shapiro G, Ramaiya 
NH. Personalized tumor response assessment in the era of molecular medicine: 
cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST.  
AJR Am J Roentgenol  2012;198(4):737–745.
5. Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS. Optimizing immune-related 
tumor response assessment: does reducing the number of lesions impact response 
assessment in melanoma patients treated with ipilimumab?  J Immunother Cancer  
2014;2:17.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 148
Appendix 5. Guidelines for Evaluation of Bone Scans
Based on Prostate Cancer Working Group 3.38
An international expert committee of prostate cancer clinical investigators (the Prostate 
Cancer Clinical Trials Working Group 3 [PCWG3]) was reconvened and expanded and met 
in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation 
studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.
Given the frequency of bone involvement in patients with progressive, castration-resistant 
disease, the decreased emphasis of early changes in PSA, and the increased availability of 
cytostatic agents, reliable methods to assess changes in bone are of increasing importance. 
PCWG3 recognizes that standards for using MRI and PET to assess bone metastases are 
under active investigation, so only radionuclide bone scans are considered here.
PCWG3 also recognizes that there are no validated criteria for response on radionuclide bone 
scan. 
For control/relieve/eliminate end points, the PCWG3 recommends that post-treatment 
changes be recorded “no new lesions,” “new lesions” or “resolved bone lesion.” However, 
progression at the first scheduled assessment should be confirmed on a second scan 
performed 6 or more weeks later, in the absence of clearly worsening disease or 
disease-related symptoms. In the event of visible lesions disappearing, this should also be 
confirmed at the next scheduled assessment. 
For prevent/delay end points, progressing disease on bone scan is considered when at least
two new lesions relative to the first post-treatment scan is confirmed on a subsequent scan.  
PCWG3 does not recommend performing a follow-up bone scan before 12 weeks of 
treatment unless clinically indicated. At the first 12-week reassessment, defining disease
progression requires a confirmatory scan (which shows additional new lesions compared 
with the first follow-up scan) performed 6 or more weeks later, because lesions visible at the 
first 12-week assessment may represent disease that was not detected on the pretreatment 
scan. When further progression is documented on the confirmatory scan, the date of 
progression recorded for the trial, is the date of the first scan that shows the change. 
Nonmetastatic to metastatic progression: Any new unequivocal bone lesion, except if that 
lesion appears in the first post-treatment scan; in that case, document the event, continue 
treatment until 2 additional new lesions appear, and record both events.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 149
Appendix 6. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE)
The NCI CTCAE (Version 4.03 dated June 14, 2010) has been placed in the Study Manual 
for this protocol.  Alternatively, the NCI CTCAE may be reviewed on-line at the following 
NCI website: http://ctep.cancer/gov/reporting.ctc.html.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 150
Appendix 7. Management of Immune-related Adverse Events (irAEs) including
Myasthenia Gravis
Note: References to study treatment in the table below refer to PF-06801591 and/or 
tremelimumab.
Gastrointestinal irAEs
Severity of Diarrhea/Colitis
(NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 1
Diarrhea: <4 stools/day over Baseline.
Colitis: asymptomatic.
-Continue study treatment.
-Symptomatic treatment
(eg, loperamide).
-Close monitoring for worsening
symptoms.
-Educate patient to report 
worsening immediately.
-If worsens:
Treat as Grade 2, 3 or 4.
Grade 2
Diarrhea: 4 to 6 stools per day over
Baseline; IV fluids indicated <24 hours; 
not interfering with ADL.
Colitis: abdominal pain; blood in stool.
-Withhold study treatment.
-Symptomatic treatment.
-If improves to Grade 1: Resume 
study treatment.
-If persists >5-7 days or recurs:
Treat as Grade 3 or 4.
Grade 3 to 4
Diarrhea (Grade 3): 7 stools per day over 
Baseline; incontinence; IV fluids 24 h; 
interfering with ADL.
Colitis (Grade 3): severe abdominal pain, 
medical intervention indicated, peritoneal
signs.
Grade 4: life-threatening, perforation.
-Withhold for Grade 3.
-Permanently discontinue 
study treatment for Grade 4 or 
recurrent Grade 3.
-1.0 to 2.0 mg/kg/day 
prednisone IV or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider lower endoscopy.
-If improves:
-Continue steroids until Grade 1, 
then taper over at least 1 month;
resume study treatment following
steroids taper (for initial Grade 3).
-If worsens, persists >3 to 5 days, or
recurs after improvement:
-Add infliximab 5 mg/kg (if no 
contraindication).
-Note: infliximab should not be
used in cases of perforation or 
sepsis.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 151
Dermatological irAEs
Grade of Rash 
(NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 1 to 2
Covering 30% body surface 
area.
-Continue study treatment.  
-Symptomatic therapy (for 
example, antihistamines, topical 
steroids).
-If persists >1 to 2 weeks or recurs: 
-Withhold  study treatment.
-Consider skin biopsy.
-Consider 0.5-1.0 mg/kg/day 
prednisone or equivalent. Once 
improving, taper steroids over at least 
1 month, consider prophylactic 
antibiotics for opportunistic infections, 
and resume study treatment following 
steroids taper.
-If worsens: Treat as Grade 3 to 4.
Grade 3 to 4
Grade 3: Covering >30% body
surface area;
Grade 4: Life threatening 
consequences.
-Withhold study treatment for
Grade 3.
-Permanently discontinue for
Grade 4 or recurrent Grade 3.
-Consider skin biopsy.
-Dermatology consult.
-1.0 to 2.0 mg/kg/day prednisone
or equivalent.
-Add prophylactic antibiotics for
opportunistic infections.
-If improves to Grade 1:
-Taper steroids over at least 1 month; 
resume study treatment following 
steroids taper (for initial Grade 3).

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 152
Pulmonary irAEs
Grade of Pneumonitis (NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 1
Radiographic changes only.
-Consider withholding study 
treatment.
-Monitor for symptoms every 
2 to 3 days.
-Consider Pulmonary and
Infectious Disease consults.
-Re-assess at least every 3 weeks
-If worsens: Treat as Grade 2 or
Grade 3 to 4.
Grade 2
Mild to moderate new symptoms.
-Withhold study treatment.
-Pulmonary and Infectious 
Disease consults.
-Monitor symptoms daily; 
consider hospitalization.
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider bronchoscopy, lung
biopsy.
-Re-assess every 1 to 3 days If
improves:
-When symptoms return to
Grade 1, taper steroids over at 
least 1 month, and then resume 
study treatment following steroids 
taper.
-If not improving after 2 weeks or
worsening: Treat as Grade 3 to 4.
Grade 3 to 4
Grade 3: Severe new symptoms;
New/worsening hypoxia;
Grade 4: Life-threatening.
-Permanently discontinue 
study treatment.
-Hospitalize.
-Pulmonary and Infectious 
Disease consults.
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider bronchoscopy, lung
biopsy.
-If improves to Grade 1:
-Taper steroids over at least
1 month.
-If not improving after 48 hours or 
worsening: Add additional
immunosuppression (for example,
infliximab, cyclophosphamide, IV
immunoglobulin, or mycophenolate
mofetil).

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 153
Hepatic irAEs
Grade of Liver Test
Elevation (NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 1
Grade 1 AST or ALT > ULN
to 3.0 x ULN and/or Total
bilirubin > ULN to
1.5 x ULN.
-Continue study treatment.
-Continue liver function monitoring.
-If worsens: Treat as Grade 2 or 3 – 4.
Grade 2
AST or ALT >3.0 to 
5 x ULN and/or total 
bilirubin >1.5 to 3 x ULN.
-Withhold study treatment.
-Increase frequency of monitoring to 
every 3 days.
-If returns to Grade 1:
-Resume routine monitoring; resume study 
treatment.
-If elevation persists >5 to 7 days or 
worsens: 
-Treat as Grade 3 to 4.
Grade 3 to 4
AST or ALT >5 x ULN
and/or total bilirubin 
>3 x ULN.
-Permanently discontinue study 
treatment.
-Increase frequency of monitoring to 
every 1 to 2 days.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections.
-Consult gastroenterologist/ 
hepatologist.
-Consider obtaining MRI/CT scan of 
liver and liver biopsy if clinically 
warranted.
-If returns to Grade 1:
-Taper steroids over at least 1 month.
-If does not improve in >3 to 5 days, 
worsens or rebounds:
-Add mycophenolate mofetil 1 gram (g) 
twice daily.
-If no response within an additional 3 to 
5 days, consider other 
immunosuppressants per local guidelines.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 154
Renal irAEs
Grade of Creatinine Increased
(NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 1
Creatinine increased > ULN to
1.5 x ULN.
-Continue study treatment.
-Continue renal function 
monitoring.
-If worsens: Treat as 
Grade 2 to 3 or 4.
Grade 2 to 3
Creatinine increased >1.5 and
6 x ULN.
-Withhold study treatment.  
-Increase frequency of monitoring to
every 3 days.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections.
-Consider renal biopsy.
-If returns to Grade 1:
-Taper steroids over at least 
1 month, and resume study 
treatment following steroids 
taper.
-If worsens:
-Treat as Grade 4.
Grade 4
Creatinine increased >6 x ULN.
-Permanently discontinue study treatment.
-Monitor creatinine daily.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections Consider renal 
biopsy.
-Nephrology consult.
-If returns to Grade 1:
Taper steroids over at least 
1 month.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 155
Cardiac irAEs
Myocarditis
Initial Management
Follow-up Management
New onset of cardiac signs or
symptoms and/or new laboratory
cardiac biomarker elevations 
(eg, troponin, CK-MB, BNP) or 
cardiac imaging abnormalities 
suggestive of myocarditis.
-Withhold study treatment.
-Hospitalize.
-In the presence of life threatening cardiac 
decompensation, consider transfer to a 
facility experienced in advanced heart failure 
and arrhythmia management.
-Consult cardiologist to establish etiology
and rule-out immune-mediated myocarditis.
-Guideline based supportive treatment as per 
cardiology consult.*
-Consider myocardial biopsy if
recommended per cardiology consult.
-If symptoms improve
and immune-mediated
etiology is ruled out,
re-start study treatment.
-If symptoms do not 
improve/worsen, viral 
myocarditis is excluded, 
and immune-mediated
etiology is suspected or 
confirmed following 
cardiology consult, 
manage as 
immune-mediated
myocarditis.
Immune-mediated myocarditis.
-Permanently discontinue study treatment.
-Guideline based supportive treatment as
appropriate as per cardiology consult.*
1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections.
-Once improving, taper
steroids over at least 
1 month.
If no improvement or 
worsening, consider 
additional 
immunosuppressants
(eg, azathioprine,
cyclosporine A).
*Local guidelines, or eg, ESC or AHA guidelines
ESC guidelines website: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines AHA guidelines 
website:
http://professional.heart.org/professional/GuidelinesStatements/searchresults.jsp?q=&y=&t=1001

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 156
Endocrine irAEs
Endocrine Disorder
Initial Management
Follow-up Management
Grade 1 or 
Grade 2 endocrinopathies
(hypothyroidism,
hyperthyroidism, adrenal
insufficiency, type I diabetes
mellitus).
-Continue study treatment.
-Endocrinology consult if needed.
-Start thyroid hormone replacement therapy 
(for hypothyroidism), anti-thyroid treatment 
(for hyperthyroidism), corticosteroids (for
adrenal insufficiency) or insulin (for Type I 
diabetes mellitus) as appropriate.
-Rule-out secondary endocrinopathies 
(ie, hypopituitarism/hypophysitis).
-Continue hormone 
replacement/suppression and 
monitoring of endocrine 
function as appropriate.
Grade 3 or Grade 
4 endocrinopathies
(hypothyroidism,
hyperthyroidism, adrenal
insufficiency, type I diabetes
mellitus).
-Withhold study treatment.
-Consider hospitalization.
-Endocrinology consult.
-Start thyroid hormone replacement therapy 
(for hypothyroidism), anti-thyroid treatment 
(for hyperthyroidism), corticosteroids (for
adrenal insufficiency) or insulin (for type I 
diabetes mellitus) as appropriate.
-Rule-out secondary endocrinopathies 
(ie, hypopituitarism/hypophysitis).
-Resume study treatment once 
symptoms and/or laboratory 
tests improve to Grade 1
(with or without hormone
replacement/suppression).
-Continue hormone 
replacement/suppression and 
monitoring of endocrine 
function as appropriate.
Hypopituitarism/ 
Hypophysitis (secondary
endocrinopathies).
-If secondary thyroid and/or adrenal 
insufficiency is confirmed (ie, subnormal
serum FT4 with inappropriately low TSH 
and/or low serum cortisol with 
inappropriately low ACTH):
-Refer to endocrinologist for dynamic 
testing as indicated and measurement of 
other hormones (FSH, LH, GH/IGF-1,
PRL, testosterone in men, estrogens in 
women).
-Hormone replacement/suppressive
therapy as appropriate.
-Perform pituitary MRI and visual field 
examination as indicated.
-If hypophysitis is confirmed:
-Continue study treatment if mild 
symptoms with normal MRI. Repeat the 
MRI in 1 month.
-Withhold study treatment if moderate,
severe or life-threatening symptoms of 
hypophysitis and/or abnormal MRI.
Consider hospitalization. Initiate 
corticosteroids (1 to 2 mg/kg/day 
prednisone or equivalent) followed by 
corticosteroids taper during at least 
1 month.
-Add prophylactic antibiotics for
opportunistic infections.
-Resume study treatment once 
symptoms and hormone tests
improve to Grade 1 (with or 
without hormone
replacement).
-In addition, for hypophysitis 
with abnormal MRI, resume
study treatment only once 
shrinkage of the pituitary
gland on MRI/CT scan is 
documented.
-Continue hormone 
replacement/suppression 
therapy as appropriate.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 157
Other irAEs (not described above)
Grade of other irAEs 
(NCI-CTCAE v4)
Initial Management
Follow-up Management
Grade 2 or Grade 3 clinical signs
or symptoms suggestive of a
potential irAE.
-Withhold study treatment pending
clinical investigation.
-If irAE is ruled out, manage as
appropriate according to the 
diagnosis and consider re-starting 
study treatment.
-If irAE is confirmed, treat as
Grade 2 or 3 irAE.
Grade 2 irAE or first occurrence 
of Grade 3 irAE.
-Withhold study treatment.
-1.0 to 2.0 mg/kg/day prednisone  or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections.
-Specialty consult as appropriate.
-If improves to Grade 1:
-Taper steroids over at least 
1 month and resume study 
treatment following steroids taper.
Recurrence of same Grade 3
irAEs.
-Permanently discontinue study 
treatment.
-1.0 to 2.0 mg/kg/day prednisone or
equivalent.
-Add prophylactic antibiotics for 
opportunistic infections.
-Specialty consult as appropriate.
-If improves to Grade 1:
Taper steroids over at least 
1 month.
Grade 4.
-Permanently discontinue study 
treatment.
-1.0 to 2.0 mg/kg/day prednisone  or 
equivalent and/or other 
immunosuppressant as needed.
-Add prophylactic antibiotics for 
opportunistic infections.
-Specialty consult.
-If improves to Grade 1:
Taper steroids over at least 
1 month.
Requirement for 10 mg per day 
or greater prednisone or 
equivalent for more than 
12 weeks for reasons other than 
hormonal replacement for 
adrenal insufficiency.
Persistent Grade 2 or 3 irAE 
lasting 12 weeks or longer.
-Permanently discontinue study 
treatment.
-Specialty consult.
Abbreviations: ACTH=adrenocorticotropic hormone; ADL=activities of daily living; ALT=alanine aminotransferase;
AST=aspartate aminotransferase; BNP=B-type natriuretic peptide; CK-MB=creatine kinase MB; CT= computed
tomography; FSH=follicle-stimulating hormone; GH=growth hormone; IGF-1=insulin-like growth factor 1;
irAE=immune-related adverse event; IV=intravenous; LH=luteinizing hormone; MRI=magnetic resonance imaging;
NCI-CTCAE=National Cancer Institute-Common Terminology Criteria for Adverse Events; PRL=prolactin; T4=thyroxine; 
TSH=thyroid-stimulating hormone; ULN=upper limit of normal.

PF-06753512
B7791001
Final Protocol Amendment 8, 29 May 2020
PFIZER CONFIDENTIAL
Page 158