A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men With Localized Intermediate- and High-Risk Prostate Cancer
Phase: PHASE2
Conditions: Prostate Cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Neoadjuvant Enoblituzumab (MGA271) 
             IRB#: IRB00103776 
Johns Hopkins University 
 
Protocol Version 4.0 (Amendment 4) / Version Date: 06/08/20210 
  
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A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with 
Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB00103776 
IND #: 131012      NCT02923180 
Johns Hopkins University 
 
Principal Investigator 
Emmanuel Antonarakis, MD 
Johns Hopkins Kimmel Cancer Center, Oncology 
Email: eantona1@jhmi.edu 
 
Co-Principal Investigator  
Eugene Shenderov, MD DPhil 
Johns Hopkins Kimmel Cancer Center, Oncology 
Email: Eugene.Shenderov@jhmi.edu 
 
Co-Investigators 
Drew Pardoll, MD PhD 
Johns Hopkins Kimmel Cancer Center, Oncology 
Email: dpardoll1@jhmi.edu 
 
Mohamad E. Allaf, MD 
Johns Hopkins Kimmel Cancer Center, Urology 
Email: mallaf@jhmi.edu 
 
Angelo DeMarzo, MD PhD 
Johns Hopkins Kimmel Cancer Center, Pathology 
Email: ademarz@jhmi.edu 
 
 
 
 
Statistician 
Hao Wang, PhD 
Johns Hopkins Kimmel Cancer Center 
 
  
 
 
 
 
 
 
 
Protocol Version 4.0 (Amencdment 4) / Version Date: 06/08/2021 
CONFIDENTIALITY STATEMENT 
The information in this document is provided to you as an investigator, potential investigator, consultant, 
or contractor, for review by you, your staff, and the appropriate Institutional Review Board or Ethics 
Committee. By accepting this document, you agree that the information contained herein will not be 
disclosed to others without written authorization from the lead site/sponsor, except to the extent 
necessary to initiate the study or conduct study-related activities. 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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SYNOPSIS 
Title 
A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized 
Intermediate- and High-Risk Prostate Cancer 
Institution 
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 
PI(s) 
Emmanuel S. Antonarakis, MD (PI), Eugene Shenderov, MD DPhil (Co-PI). 
Sponsor 
MacroGenics, Inc. 
9704 Medical Center Drive 
Rockville, MD 20850 
IRB # 
IRB00103776 
Study agent 
Enoblituzumab (also referred to as MGA271) 
 
Phase 
Phase II 
Indication 
Men with intermediate and high-risk localized prostate cancer, prior to radical 
prostatectomy 
Target 
population 
Inclusion criteria 
• 
Histologically confirmed prostate adenocarcinoma 
• 
Clinical stage T1c–T3b, N0, M0 
• 
Gleason sum 7-10 
• 
At least 2 positive cores 
• 
Prior decision to undergo radical prostatectomy 
• 
Adult male >18 years of age 
• 
ECOG performance status 0-1, or Karnofsky score ≥ 70% 
• 
Adequate kidney, liver, and bone marrow function 
• 
Willingness to sign informed consent and adhere to study requirements 
Exclusion criteria: 
• 
Presence of known lymph node involvement or distant metastases 
• 
Prior radiation, hormones, biologics, or chemotherapy for prostate cancer 
• 
Prior immunotherapy/vaccine therapy for prostate cancer 
• 
Prior use of experimental agents for prostate cancer 
• 
Concomitant treatment with hormonal therapy or 5-reductase inhibitors 
• 
History of autoimmune disease requiring systemic immunosuppression 
• 
History of other malignancy within 3 years 
• 
Uncontrolled major infectious, cardiovascular, pulmonary, hematologic, or 
psychiatric illnesses that would make the patient a poor study candidate 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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Start date/ 
Duration 
Initial patients are expected to be entered in November 2016. With an estimated 
enrollment rate of 3 patients per month, accrual is expected to last 5-6 months. 
The trial was originally designed to evaluate safety and PD endpoint with 16 patients. 
Based on promising PSA response data prior to prostatectomy, following 
Enoblituzumab therapy alone, the study will enroll an additional 16 patients for a total 
size of 32 – amendment 1. All patients will be enrolled utilizing identical inclusion, 
exclusion, and treatment conditions as the first 16 patients. Expanding the trial to enroll 
a total of 32 patients will provide statistical power to estimate the clinical benefit of 
Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) 12 months following 
radical prostatectomy. 
Sample size 
16 evaluable patients (i.e. those that undergo prostatectomy) 
16 additional patients in the expansion Amendment 1 will be enrolled for a total sample 
size of 32 patients.  
Rationale 
Prostate cancer remains the second most common cause of cancer related death in 
males, killing one in every 36 American men.  While advances have been made in early 
detection and local treatment, few treatments have been able to dramatically alter the 
course of disease once it progresses to subclinical or clinical metastases.  In that setting, 
androgen deprivation therapy is considered frontline but, while many patients will 
experience initial tumor regression, their prostate cancer inevitably develops a castrate 
resistant phenotype.  Recent advances in our understanding and ability to manipulate 
the immune system have resulted in a sea of change in the treatment of aggressive 
malignancies.  One promising approach to metastatic disease involves treatments that 
use the immune system to target and destroy tumor cells. Because an anti-tumor T cell 
response has the ability to dynamically evolve, immunotherapy can potentially 
overcome the genetic diversity of aggressive and advanced cancers.  Moreover, because 
the immune system develops memory, anti-tumor immune responses can be potentially 
long-lived, and long-lived responses have been reported in patients with melanoma, 
kidney cancer and bladder cancer.  Those recent data mostly involve immune 
checkpoint blockade using anti-CTLA-4 or anti-PD1/PDL1; but in prostate cancer those 
therapies have yielded little in the way of objective responses, suggesting the need for 
alternative immunological approaches. 
B7-H3 is part of the B7 superfamily which includes B7-H1(PD-L1) and B7-DC(PD-L2).  
Although a number of studies document a role for B7-H3 in modulating the immune 
response, its regulation and mechanism of action are not completely clear, with 
literature demonstrating both T-cell stimulatory and inhibitory effects.  In addition, 
tumor cell expression of B7-H3 has been associated with an autonomous proliferative 
and migratory function.  Perhaps most relevant, multiple reports (as well as our 
unpublished data) support a correlation between B7-H3 expression and adverse 
pathology and clinical outcome in men with prostate cancer.  Using a large series of 
surgical specimens in a cohort of men uncontaminated by hormonal therapy, we found 
that B7-H3 expression correlates with stage and is associated with biochemical and 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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clinical progression following treatment.  In addition, B7-H3 levels remain high in the 
presence of androgen deprivation.  These studies suggest a potential role for B7-H3 in 
prostate cancer progression and support its use as therapeutic target in both the 
hormone naïve and castrate resistant state.  Here we propose a neoadjuvant study to 
determine the anti-tumor, immunological and biological effects of B7-H3 inhibition in 
men with high-risk prostate cancer. 
We aim (1) to investigate whether inhibition of B7-H3 via administration of 
Enoblituzumab is safe and feasible in the neoadjuvant setting for men with localized 
intermediate and high-risk prostate cancer; (2) to determine whether Enoblituzumab 
produces anti-tumor responses by evaluating tumor cell apoptosis in harvested prostate 
glands; and (3) to determine whether Enoblituzumab is immunogenic in men with 
localized prostate cancer by evaluating T-cell infiltration in harvested prostate glands. 
We hypothesize that neoadjuvant Enoblituzumab will be feasible and safe (i.e. will not 
interfere with subsequent prostatectomy), and will produce measurable tumor cell 
death and antitumor immune responses. 
If this study shows significant tumor cell apoptosis and enhancement of antitumor 
immunity with Enoblituzumab, and administration of the study drug is feasible and safe, 
then future studies would aim to use Enoblituzumab in both the adjuvant and the 
salvage settings. For example, a trial could be designed to assess the efficacy of 
Enoblituzumab given before and after radical prostatectomy, using PSA recurrence as 
the primary endpoint. Alternatively, a trial of Enoblituzumab for patients with PSA 
recurrence could be designed, with metastatic progression as the primary endpoint. 
Objectives 
Primary: 
• 
To confirm the safety and feasibility of Enoblituzumab administered using a 
standard dose / schedule in the neo-adjuvant setting 
In the expansion cohort (Amendment 1): 
• 
PSA0 Response (Undetectable PSA level <0.1 ng/mL) at 12 months following radical 
prostatectomy 
 
Secondary: 
• 
To quantify an anti-tumor response to Enoblituzumab 
o TUNEL staining and quantification of tumor cell apoptosis 
o Caspase 3 staining 
o FcGamma Staining (RIIA, RIIB, RIII/RIV) (based on proposed MOA) 
o Pathological response graded according to standard criteria 
• 
To assess the immune response to Enoblituzumab 
o Quantification of CD8 T cell and CD4 T cell infiltration into the tumor / 
peritumoral area 
o Determine the effect of Enoblituzumab treatment on the CD8 / Treg and 
CD4 / Treg ratios 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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• 
To assess Gleason grade change post neoadjuvant Enoblituzumab treatment, by 
comparing prostatectomy Gleason sum to pre-treatment biopsy Gleason sum 
• 
To quantify the extent of PD-L1+ cell density in the prostate from harvested 
prostate glands of treated patients. 
• 
To quantify the NK cell density in tumor tissue from harvested prostate glands 
of patients 
• 
To quantify tissue androgen concentration (testosterone, dihydrotestosterone) 
and androgen receptor (AR) protein expression in prostate specimens 
Exploratory: 
• 
To quantify B7-H3 expression in pre-treatment and post-treatment tumor tissue 
and correlate with tumor cell apoptosis and time to PSA-recurrence 
• 
To quantify PD-1, LAG3 and TIM3 in pre and post treatment tumor tissue 
• 
Determination of Fc receptor genotype (CD16A, CD32A, CD32B) 
• 
Global expression profiling of pre and post treatment tumor tissue using the 
immune NanoString immunopanel and Affy microarrays 
• 
TCR Deep Sequencing (Adaptive Biotech) testing hypothesis that successful anti-
tumor response modulates TCR repertoire in peripheral and tumor infiltrating 
lymphocytes. 
• 
Quantification of antigen-spread using ProtoArray analyses 
 
Study design 
This is a single-center, single arm, open-label pilot study evaluating the safety, anti-
tumor effect, and immunogenicity of neoadjuvant Enoblituzumab (MGA271) given prior 
to radical prostatectomy in men with intermediate and high-risk localized prostate 
cancer. Patients will be recruited from the outpatient Urology clinic. Eligible patients 
will receive Enoblituzumab at a dose of 15mg/kg IV given weekly for 6 doses beginning 
50 days prior to radical prostatectomy. 14 days after the last dose of Enoblituzumab, 
prostate glands will be harvested at the time of radical prostatectomy, and prostate 
tissue will be examined for the secondary endpoints.  Follow-up evaluation for adverse 
events will occur 30 days and 90 days after surgery. Patients will then be followed by 
their urologists according to standard institutional practices, but will require PSA 
evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-
3. 
 
        Study Schema: 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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.
  
 
 
Baseline evaluations: 
• 
Informed consent 
• 
Medical history and physical assessment 
• 
Review of medications 
• 
Vital signs, including height and weight 
• 
Performance status 
• 
Central pathologic review of prostate core biopsies for histological diagnosis and 
Gleason score  
• 
CT (If allergic to CT scan contrast, obtain MRI with contrast) and/or bone scan, if 
clinically indicated 
• 
Hematology, coagulation, and chemistry laboratories 
• 
Serum PSA measurement 
• 
Sera for immunoassays 
 
On weekly treatment days (days 1, 8, 15, 22, 29, 36): 
• 
Performance status 
• 
Interval history and focused physical assessment (including vital signs) 
• 
Adverse events/toxicity evaluation 
• 
Hematology and chemistry laboratories 
• 
PBMC collection for TCR repertoire 
• 
Fc Receptor Genotyping on day one  
• 
Blood for PBLs (treatment days 1 and 36 only) 
• 
Administration of Enoblituzumab 15mg/kg IV 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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On day 50: 
• 
Medical history and focused physical assessment (including vital signs) 
• 
Review of medications 
• 
Performance status 
• 
Adverse events/toxicity evaluation 
• 
Hematology and chemistry laboratories 
• 
Serum PSA 
• 
Sera for immunoassays 
• 
PBMC collection for TCR repertoire 
• 
Radical prostatectomy 
• 
Pathologic review of surgical specimen according to standard procedures 
• 
Evaluation of harvested prostate gland for tumor cell apoptosis and CD8+ T cell 
infiltration and other secondary endpoints 
Post-operative day 30 and day 90: 
• 
Performance status 
• 
Adverse events/toxicity evaluation 
• 
Hematology and chemistry laboratories 
• 
PSA every 3 months (post-op year 1), then every 6 months (post-op years 2-3) 
• 
Sera for immunoassays 
• 
PBMC collection for TCR repertoire 
• 
Blood for PBLs (Post-op day 30 only) 
Criteria for 
evaluation 
Primary endpoint:  
• 
Frequency, type, and severity of adverse events 
In expansion (Amendment 1): 
• 
PSA0 Response (Undetectable PSA level <0.1 ng/mL) at 12 months following radical 
prostatectomy 
Secondary endpoints:  
• 
Mean levels of apoptotic markers (TUNEL staining, caspase 3 staining, and 
FcGamma staining) and proliferation markers (Ki-67) in prostate tumor specimens 
of treated patients  
• 
Mean CD8+ T cell density in tumor tissue from harvested prostate glands of patients 
• 
To quantify the extent of PD-L1+ cell density in the prostate from harvested prostate 
glands of treated patients 
• 
Mean Treg density in tumor tissue from harvested prostate glands of patients 
• 
Mean CD8+/Treg and CD4+/Treg ratios in tumor tissue from harvested prostate glands 
of patients  
• 
Mean CD4+ T cell density in tumor tissue from harvested prostate glands of patients 
• 
Mean NK cell density in tumor tissue from harvested prostate glands of patients 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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• 
Proportion of treated patients with detectable Enoblituzumab in prostate tumor 
specimens(fresh frozen section) 
• 
Proportion of pathological complete responses (pCR) in each treatment group 
• 
Proportion of patients achieving a PSA response rate (PSA <0.1 ng/mL) at 3 months 
after prostatectomy 
• 
Median time-to-PSA-recurrence (PSA ≥0.2 ng/mL) after radical prostatectomy 
• 
Median PSA decrease prior to radical prostatectomy 
• 
To assess Gleason grade change post neoadjuvant Enoblituzumab treatment, by 
comparing prostatectomy Gleason sum to pre-treatment biopsy Gleason sum 
 
 
 
Statistical 
methods 
Our primary objective(s) is to characterize safety, tolerability, and feasibility of 
treatment of men with Enoblituzumab in the neoadjvuant setting as well as obtain an 
estimate of PSA0 response rate 12 months following radical prostatectomy.  The trial 
will monitor toxicity and safety, as well as feasibility with respect to its impact on 
subsequent surgery.   The secondary objective will be to evaluate an anti-tumor effect 
consistent with the agent’s proposed mechanism of action (MOA), antibody-dependent 
cellular cytotoxicity (ADCC).  Tumor cell death will be quantified by Caspase staining, 
and post-treatment apoptotic index compared with that from the pre-treatment biopsy. 
Sample size is driven by detecting a pharmacodynamic effect of the agent based on the 
key secondary endpoint of tumor cell death as well as in the expansion cohort to obtain 
an estimate of PSA0 response.  A biologically meaningful treatment effect will be deemed 
to be one where the tumor cell apoptosis is two-fold higher after Enoblituzumab 
therapy. Previous study showed that baseline apoptosis, measured by Caspase staining, is 
0.06 +/- 0.08 (Mean +/-SD) for Gleason 4 and 0.2 ± 0.2 for Gleason 3 (Kim et al 2016). Based 
on this data, we assume that the coefficient of variation of tumor cell death measure is 
1.2 and the correlations between the measures pre- and post-treatment is moderate at 
0.4, 16 subjects will provide 88% power to detect a 2-fold increase in apoptotic tumor 
cells after the treatment compared to baseline, using a one-sided paired t-test with 
significance level 0.05.   Other endpoints will be exploratory in nature, and quantified 
using descriptive statistics.  
 
For the expansion cohort (amendment 1): 
Our primary efficacy endpoint with 32 patients will be to estimate the clinical benefit of 
neoadjuvant Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) at 12 
months following radical prostatectomy. There are currently no approved neoadjuvant 
treatments for high risk localized prostate cancer and we believe future larger 
neoadjuvant trials can be better designed in high risk patients if we can estimate the 
benefit as per the below table showing the 90% confidence interval.  

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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Observed N with 
undetectable PSA 
Observed 
rate 
90% CI 
0 
0 
0% - 7.8% 
1 
3.1% 
0.7% - 12.9% 
2 
6.2% 
2.1% - 17.2% 
3 
9.4% 
3.8% - 21.3% 
 
Safety analysis 
 
Frequency, types, and grades of adverse events in each treatment group will be 
measured using the NCI Common Toxicity Criteria version 4.0, and will be summarized 
using descriptive statistics. Formal safety assessments will be performed from the time 
of first administration of Enoblituzumab until the 90th postoperative day. 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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TABLE OF CONTENTS 
 
1. 
OBJECTIVES ................................................................................................................................................................... 16 
1.1 
Primary Objectives ............................................................................................................................................................. 16 
1.2 
Secondary Objectives ........................................................................................................................................................ 16 
1.3 
Exploratory Objectives ..................................................................................................................................................... 16 
2. 
BACKGROUND AND RATIONALE ........................................................................................................................... 18 
2.1 
Disease Background .......................................................................................................................................................... 18 
2.2 
Treatment Background .................................................................................................................................................... 19 
2.3 
Rationale ................................................................................................................................................................................. 23 
3. 
PATIENT SELECTION ................................................................................................................................................. 25 
3.1 
Target Population ............................................................................................................................................................... 25 
3.2 
Inclusion Criteria ................................................................................................................................................................ 25 
3.3 
Exclusion Criteria................................................................................................................................................................ 26 
3.4 
Inclusion of Minorities ...................................................................................................................................................... 26 
3.5 
Prohibited Concomitant Medications ........................................................................................................................ 27 
4. 
REGISTRATION AND ENROLLMENT PLAN ......................................................................................................... 27 
4.1 
Registration Procedure .................................................................................................................................................... 27 
4.2 
Expected Enrollment ......................................................................................................................................................... 28 
4.3 
Study Centers ........................................................................................................................................................................ 28 
4.4 
Recruitment........................................................................................................................................................................... 28 
5. 
STUDY PLAN ................................................................................................................................................................. 28 
5.1 
Overview and Schema ...................................................................................................................................................... 28 
5.2 
Screening/Pretreatment Evaluation .......................................................................................................................... 32 
5.3 
Treatment Visits .................................................................................................................................................................. 32 
5.4 
Radical Prostatectomy ...................................................................................................................................................... 33 
5.5 
Follow-Up Evaluations ..................................................................................................................................................... 33 
5.6 
Duration of Therapy .......................................................................................................................................................... 34 
6. 
STUDY TREATMENT .................................................................................................................................................. 34 
6.1 
Description of Study Drug and Supplies ................................................................................................................... 34 
6.2 
Drug Preparation ................................................................................................................................................................ 35 
7. 
ADVERSE EVENTS AND REPORTING REQUIREMENTS................................................................................... 42 
7.1 
Recording and Grading ..................................................................................................................................................... 42 
7.2 
Unexpected Adverse Events........................................................................................................................................... 44 
7.3 
Serious Adverse Events and Serious Adverse Drug Reactions ....................................................................... 44 
7.4 
Perioperative Adverse Events ....................................................................................................................................... 45 
7.5 
Reporting Adverse Events .............................................................................................................................................. 46 
7.6 
Pregnancy ............................................................................................................................................................................... 48 
8. 
OUTCOME ASSESSMENT ........................................................................................................................................... 48 
8.1 
Radical Prostatectomy Specimen ................................................................................................................................ 48 
8.2 
Primary Endpoint ............................................................................................................................................................... 49 
8.3 
Secondary Endpoints ........................................................................................................................................................ 49 
9. 
REGULATORY AND REPORTING REQUIREMENTS .......................................................................................... 53 
9.1 
Regulatory Responsibilities ........................................................................................................................................... 53 
9.2 
Data Management ............................................................................................................................................................... 54 
9.3 
Study Monitoring and Quality Assurance ................................................................................................................ 54 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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10. 
STATISTICAL CONSIDERATIONS ........................................................................................................................... 55 
10.1 Study Design and Sample Size ....................................................................................................................................... 55 
10.2 Study Endpoints .................................................................................................................................................................. 55 
10.4 Safety Analysis ..................................................................................................................................................................... 59 
11. 
PROTECTION OF HUMAN SUBJECTS..................................................................................................................... 60 
11.1 Ethical Considerations ...................................................................................................................................................... 60 
11.2 Protocol Amendments ...................................................................................................................................................... 60 
11.3 Written Informed Consent .............................................................................................................................................. 60 
11.4 Protection of Privacy ......................................................................................................................................................... 61 
11.5 Study Termination or Modification ............................................................................................................................ 61 
12. 
REFERENCES ................................................................................................................................................................. 62 
APPENDIX A:  PERFORMANCE STATUS CRITERIA ...................................................................................................... 65 
APPENDIX B:  COMMON TOXICITY CRITERIA, VERSION 4.0 .................................................................................... 66 
APPENDIX C:  SERIOUS ADVERSE EVENT (SAE) REPORTING FORM ..................................................................... 67 
APPENDIX D:  ABBREVIATIONS AND ACRONYMS ....................................................................................................... 69 
APPENDIX E:  DATA AND SAFETY MONITORING PLAN (DSMP) ........................................................................... 722 
APPENDIX F: SPECIMEN COLLECTION AND SHIPPING ............................................................................................ 723 
 
LIST OF TABLES 
Table 1 
Study Calendars 
21 
Table 2 
Intensity of Adverse Event 
32 
Table 3 
Relationship of Adverse Event to Study Drug 
32 
LIST OF FIGURES 
Figure 1 
Clinical States of Prostate Cancer 
10 
Figure 2  
MGA271 (RES242) Mediates ADCC Activity Across a Spectrum of Cancer Types 
13 
Figure 3  
Study Schema 
20 
 
 
 
Summary of changes for Protocol Amendment 1 version 1.5:  
The trial was originally designed to evaluate safety and PD endpoint with 16 patients. Based on 
promising PSA response data prior to prostatectomy, following Enoblituzumab therapy alone, the 
study will enroll an additional 16 patients for a total size of 32 – Amendment 1.  
All patients will be enrolled utilizing identical inclusion, exclusion, and treatment conditions as the 
first 16 patients. Expanding the trial to enroll a total of 32 patients will provide statistical power to 
estimate the clinical benefit of Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) 12 
months following radical prostatectomy.  
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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Section  
Changes: 
Synopsis  
Start date/ Duration:  
The trial was originally designed to evaluate safety and PD endpoint 
with 16 patients. Based on promising PSA response data prior to 
prostatectomy, following Enoblituzumab therapy alone, the study will 
enroll an additional 16 patients for a total size of 32 – amendment 1. All 
patients will be enrolled utilizing identical   inclusion, exclusion, and 
treatment conditions as the first 16 patients. Expanding the trial to 
enroll a total of 32 patients will provide statistical power to estimate 
the clinical benefit of Enoblituzumab in terms of undetectable PSA level 
(<0.1 ng/mL) 12 months following radical prostatectomy. 
Sample size: 
16 additional patients in the expansion Amendment 1 will be enrolled 
for a total sample size of 32 patients. 
Objectives:  
Primary: In the expansion cohort (Amendment 1): 
•PSA0 Response (Undetectable PSA level <0.1 ng/mL) at 12 months 
following radical prostatectomy. 
Secondary:  
•To assess Gleason grade change post neoadjuvant Enoblituzumab 
treatment, by comparing prostatectomy Gleason sum to pre-treatment 
biopsy Gleason sum 
•To quantify the extent of PD-L1+ cell density in the prostate from 
harvested prostate glands of treated patients. 
 
Criteria for evaluation: 
In expansion (Amendment 1): 
•PSA0 Response (Undetectable PSA level <0.1 ng/mL) at 12 months 
following radical prostatectomy 
•Median PSA decrease prior to radical prostatectomy 
•To assess Gleason grade change post neoadjuvant Enoblituzumab 
treatment, by comparing prostatectomy Gleason sum to pre-treatment 
biopsy Gleason sum 
 
Statistical methods: 
For the expansion cohort (amendment 1): 
Our primary efficacy endpoint with 32 patients will be to estimate the 
clinical benefit of neoadjuvant Enoblituzumab in terms of undetectable 
PSA level (<0.1 ng/mL) at 12 months following radical prostatectomy. 
There are currently no approved neoadjuvant treatments for high risk 
localized prostate cancer and we believe future larger neoadjuvant 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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trials can be better designed in high risk patients if we can estimate the 
benefit as per the below table showing the 90% confidence interval.  
 
Observed N with undetectable PSA 
Observed rate 90% CI 
0 
                                                                   0              0% - 7.8% 
1 
                                                                  3.1% 
0.7% - 12.9% 
2 
                                                                  6.2% 
2.1% - 17.2% 
3 
                                                                  9.4% 
3.8% - 21.3% 
1.1 Primary Objectives 
In expansion cohort (amendment 1): 
•To estimate PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) 
at 12 months following radical prostatectomy 
1.2 Secondary Objectives 
•To quantify the extent of PD-L1+ cell density in the prostate from 
harvested prostate glands of treated patients. 
•To quantify the extent of NK cell infiltration into the prostate from 
harvested prostate glands of treated patients.  
• Enoblituzumab (MGA271) intraprostatic drug distribution in treated 
patients.  
• To assess Gleason grade change post neoadjuvant Enoblituzumab 
treatment, comparing prostatectomy Gleason sum to pre-treatment 
biopsy Gleason sum 
1.3 Exploratory Objectives 
•IHC analyses of CD137, CD16 and/or CD107A across potential immune 
infiltrate following Enoblituzumab (based on proposed MoA) 
•Tissue androgen concentrations  
•Androgen receptor (AR) quantification 
•Global expression profiling of pre and post treatment tumor tissue 
using single cell RNA sequencing, the immune NanoString immunopanel 
and/or Affy microarrays 
Table 1 Study Calendar  
Footnote C: These labs should be collected prior to treatment. 
8.2.2 In expansion cohort 
(amendment 1) 
•All subjects receiving at least one dose of the study drug will be 
assessed for  PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) 
at 12 months following radical prostatectomy 
8.3.4 PD-L1 expression 
PD-L1 expression in prostate tumor specimens will be assessed by IHC 
in the primary core specimens (pre-treatment) and in the 
prostatectomy surgical specimens (post-treatment). This endpoint will 
be expressed as the mean staining percentage of PD-L1 in tumor tissue. 
8.3.7 
Mean NK cell density in tumor tissue from harvested prostate glands of 
patients.  
The method for quantifying NK cell density from harvested prostate 
tissue is as described in Section 8.3.3. This endpoint will be expressed 
as the mean staining percentage in tumor tissue. 
8.3.19 
In expansion cohort (Amendment 1): assessment of Gleason grade 
change (prostatectomy Gleason sum vs. core biopsy Gleason sum) post 
neoadjuvant Enoblituzumab treatment 

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This will be defined by comparing highest Gleason grade from pre-
treatment biopsy versus highest Gleason grade from post-treatment 
prostatectomy. This endpoint will be expressed as the proportion of 
men achieving a Gleason score change. 
8.3.20 
Global expression profiling of pre and post treatment tumor tissue 
using single cell RNA sequencing, the immune NanoString immunopanel 
and/or microarrays 
Expression profiling will be conducted as per established protocols for 
single cell RNA seq, Nanostring, and microarray 
8.3.21 
IHC analyses of CD137, CD16 and/or CD107A across potential immune 
infiltrate following Enoblituzumab 
 
CD137, CD107A, and CD16 expression in prostate tumor specimens will 
be assessed by IHC in the prostatectomy surgical specimens (post-
treatment). This endpoint will be expressed as the mean staining 
percentage of each of these in in tumor tissue. 
 
10.1 Study Design and 
Sample Size 
In Amendment 1, the study was expended to enroll an additional 16 
patients for a total of 32 patients to continue evaluating safety and 
better estimate the clinical benefit of Enoblituzumab in terms of 
undetectable PSA level (<0.1 ng/mL) at 12 months following radical 
prostatectomy. 
10.2 Stopping rules  
Not feasible if the observed number of surgical complications is: 
 
2  
3 
4  
5  
6 
In number of patients between: 2 - 6 
7 - 14 15 - 22 23 - 30 31 - 32 
 
The operating characteristics of the first 3stopping rule are shown 
below and are based on 5000 simulations: 
Risk of surgical complication 
0.025 0.05 
0.10 
0.15 
0.20 
% of Time study stops 1.1% 
5.9% 
29.2% 57.7% 81.4% 
Expected sample size 
31.7 
30.7 
26.4 
20.9 
15.3 
 
 
10.2.1.1 For expansion 
Amendment 1 
Estimation of PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) 
at 12 months following radical prostatectomy. 
Our primary efficacy endpoint will be to estimate the clinical benefit of 
neoadjuvant Enoblituzumab in terms of undetectable PSA level (<0.1 
ng/mL) at 12 months following radical prostatectomy. The estimate and 
corresponding 90% confidence interval based on 32 patients have 
complications is listed in the table below. 
Observed N with undetectable PSA 
Observed rate 90% CI 
0 
                                                                        0 
0% - 7.8% 
1 
                                                                       3.1% 
0.7% - 12.9% 
2 
                                                                       6.2% 
2.1% - 17.2% 

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3 
                                                                       9.4% 
3.8% - 21.3% 
10.2.2 Analysis of the 
secondary  and 
exploratory endpoints 
•PD-L1+ cell density. The methods for quantifying and analyzing PD-L1 
cell density will be similar to those described for CD8+ T cell infiltration. 
Descriptive statistics and graphical summaries will be provided 
•Mean NK cell density. The methods for quantifying and analyzing NK 
cell infiltration will be similar to those described for CD8+ T cell 
infiltration. Descriptive statistics and graphical summaries will be 
provided. 
•Enoblituzumab (MGA271) drug distribution. Intraprostatic 
Enoblituzumab staining concentrations will be summarized 
descriptively. 
•Gleason grade change post neoadjuvant Enoblituzumab treatment 
from pre-treatment biopsy. This will be calculated utilizing the highest 
Gleason grade from the pre-treatment biopsy and the post-treatment 
prostatectomy.   
APPENDIX F 
1. Sera for Immunoassays : Please Ping “Vaccine Team” (pager 410-283-
0693) and the Immune Core will be notified to pick up the sample after 
draw. 
2. Peripheral blood lymphocytes (PBLs): Please Ping “Vaccine Team” 
(pager 410-283-0693) and the Immune Core will be notified to pick up 
the sample after draw. 
 

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1. 
OBJECTIVES 
1.1 
Primary Objectives 
• 
To evaluate the safety and tolerability of MGA271 administered weekly x 6 (2 weeks 
prior to prostatectomy). 
• 
To evaluate the feasibility of administering MGA271 weekly x 6 (2 weeks prior to 
prostatectomy). 
In expansion cohort (amendment 1): 
• 
To estimate PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) at 12 months 
following radical prostatectomy  
1.2 
Secondary Objectives 
• 
To quantify markers of apoptosis (TUNEL staining, caspase 3 staining, FcGamma 
staining) in prostate tumor specimens of treated patients. 
• 
To quantify markers of cell proliferation (Ki-67) in prostate tumor specimens of 
treated patients.  
• 
To quantify the extent of CD8+ T cell infiltration into the prostate from harvested 
prostate glands of treated patients. 
• 
To quantify the extent of PD-L1+ cell density in the prostate from harvested 
prostate glands of treated patients. 
• 
To quantify the extent of CD4+ T cell and Treg infiltration into the prostate in prostate 
specimens of treated patients. 
• 
To quantify CD8+/Treg and CD4+/Treg ratios in prostate specimens of treated patients. 
• 
To quantify the extent of NK cell infiltration into the prostate from harvested 
prostate glands of treated patients.  
• 
Enoblituzumab (MGA271) intraprostatic drug distribution in treated patients.  
• 
To evaluate the proportion of pathological complete responses (pCR) in prostate 
tumor specimens of treated patients. 
• 
To evaluate PSA response rates and the time-to-PSA-recurrence after radical 
prostatectomy in treated patients. 
• 
To assess Gleason grade change post neoadjuvant Enoblituzumab treatment, 
comparing prostatectomy Gleason sum to pre-treatment biopsy Gleason sum 
1.3 Exploratory Objectives 
• 
To quantify B7-H3 expression in pre and post treatment tumor tissue and correlate 
with tumor cell apoptosis and time to PSA-recurrence 
• 
To quantify PD-L1, PD-1, LAG3 and TIM3 in pre and post treatment tumor tissue 

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• 
Determination of Fc receptor genotype (CD16A, CD32A, CD32B) 
 
• 
IHC analyses of CD137, CD16 and/or CD107A across potential immune infiltrate 
following Enoblituzumab (based on proposed MoA)   
• 
Tissue androgen concentrations  
• 
Androgen receptor (AR) quantification 
• 
Global expression profiling of pre and post treatment tumor tissue using single cell 
RNA sequencing, the immune NanoString immunopanel and/or microarrays 
• 
TCR Deep Sequencing (Adaptive Biotech) testing hypothesis that successful anti-
tumor response modulates TCR repertoire 
• 
Quantification of antigen-spread using ProtoArray analyses or similar analyses 

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2. 
BACKGROUND AND RATIONALE 
2.1 
Disease Background 
Prostate cancer is the second leading cause of cancer deaths in men. Approximately one in every six 
American men will be diagnosed with the disease during his lifetime (Siegel et al. Cancer Statistics 
2012). Yet, localized prostate cancer is often curable and even metastatic disease can respond to 
treatment. 
The course of prostate cancer from diagnosis to death is best categorized as a series of clinical states 
(Figure 1). These clinical states involve the complex interplay of a network of signaling molecules 
that collectively promote net cell proliferation relative to cell death. Based on the extent of disease, 
hormonal status, and absence or presence of detectable metastases on imaging studies, the states 
are: localized disease, rising PSA after radiation therapy or surgery with no detectable metastases, 
and clinical metastases in the non-castrate or castrate settings. 
Treatment of localized prostate cancer usually consists of surgery or radiation therapy or both. For 
patients with high-risk or locally advanced disease, a combination of radiation therapy and hormonal 
therapy is often used. However, even after definitive local therapy, approximately 30-50% of patients 
will have a local or distant recurrence (Pound et al 1999, D’Amico et al 2000). The risk of recurrence 
depends on multiple factors including tumor stage, tumor Gleason score, and serum PSA at the time 
of diagnosis. In addition, PSA doubling time at recurrence has been shown to be a powerful predictor 
of distant metastases and survival (Antonarakis et al 2012; Freedland et al 2007). 
 
Figure 1 
Clinical States of Prostate Cancer 
 
Patients with metastatic prostate cancer have a median survival of 3-7 years, and most die of the 
disease. Treatment for metastatic disease involves surgical castration or hormonal manipulation 
using luteinizing hormone-releasing hormone (LHRH) agonists/antagonists, antiandrogens, or both. 
Although the majority of these patients initially respond to androgen deprivation therapy, all 
eventually progress to a state of castration-resistant prostate cancer (CRPC).  
 
It is now accepted that CRPC is not androgen-independent and continues to rely on androgen 
signaling (Longo NEJM 2010). Owing to this new understanding, several drugs have recently 
emerged for the treatment of castration-resistant prostate cancer; these agents either suppress the 
synthesis of extragonadal androgens or target the androgen receptor directly. Enzalutamide is an 
inhibitor of androgen-receptor signaling that exerts its activity by binding avidly to the ligand-
binding domain of the androgen receptor, competing with and displacing the natural ligands of this 
receptor (testosterone and dihydrotestosterone) while also inhibiting translocation of the androgen 

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receptor into the nucleus and impairing transcriptional activation of androgen-responsive target 
genes (Tran et al. Science 2009; Scher et al. Lancet 2010). Abiraterone is an inhibitor of cytochrome 
P450 17A1 (CYP17A1) that impairs androgen-receptor signaling by depleting adrenal and 
intratumoral androgens (O’Donnell et al. Br J Cancer 2004; Attard et al. JCO 2008). After studies 
showed improved survival with these drugs, (Scher et al. NEJM 2012; de Bono et al. NEJM 2011; Ryan 
et al. NEJM 2013) both agents were approved by the Food and Drug Administration for the treatment 
of metastatic castration-resistant prostate cancer. 
 
Although enzalutamide and abiraterone represent breakthroughs in the treatment of metastatic 
castration-resistant prostate cancer, approximately 20 to 40% of patients have no response to these 
agents with respect to prostate-specific antigen (PSA) levels (i.e., they have primary resistance) 
Among patients who initially have a response to enzalutamide or abiraterone, virtually all eventually 
acquire secondary resistance. Other acceptable approaches in these men include watchful waiting 
until the development of symptoms, or the initiation of cytotoxic chemotherapy. In this regard, 
docetaxel has been shown to improve overall survival in patients with CRPC, but only by a median of 
2.9 months (Tannock et al 2004; Berthold et al 2008). However, because therapies for metastatic 
prostate cancer are palliative and not curative, there remains an urgent need to improve the outcome 
of primary therapies for prostate cancer. 
2.2 
Treatment Background 
2.2.1 
Background on B7-H3 
The B7 family of cell surface molecules consists of structurally related protein ligands that 
bind to receptors on lymphocytes and regulate immune responses. Activation of T and B 
lymphocytes is initiated by engagement of antigen-specific receptors, T cell antigen receptor 
(TcR) and membrane-bound immunoglobulin (mIg) respectively, but additional signals 
delivered simultaneously to members of the CD28 family of receptors by B7 ligands 
determine the ultimate immune response (Collins et al 2005).  B7 homolog 3 (B7-H3) is a 
novel member of the B7 family.  B7-H3 has been implicated in the delivery of both co-
stimulatory and co-inhibitory signals (Hofmeyer et al 2008). The apparent contrasting 
activities of B7-H3 may be attributed to multiple factors. While the murine B7-H3 molecule 
exists as a 2-Ig form, the human counterpart has undergone gene duplication and exists 
primarily as a 4-Ig molecule (Steinberger et al 2004). Further, as with other members of the 
B7 family, B7-H3 may bind, on different cells, to multiple receptors that remain to be 
identified. 
B7-H3 is an attractive target for tumor immunotherapy with regard to its immunological 
properties. Tissue expression studies have demonstrated that B7-H3 protein is not 
expressed in most normal tissues, rather its expression is inducible on certain antigen 
presenting cells (Suh et al 2003, Chapoval et al 2001) and vasculature, exists on certain 
endocrine tissues (most notably in the cytoplasm of epithelial cells of the adrenal cortex), 
and is over-expressed in a wide range of cancers (including cultured cancer stem-like cells). 
B7-H3 is broadly over-expressed on many malignant neoplasms, including SCCHN 
(MacroGenics unpublished observation); bladder cancer (MacroGenics unpublished 
observation, Boorjian et al 2008); prostate cancer (Zang et al 2007, Roth et al 2007, 
Thompson et al 2009, Chavin et al 2009), renal cell carcinoma (Crispen et al 2008), where 
B7-H3 is broadly expressed in tumor vasculature; ovarian cancer (Zang et al 2010); 
colorectal cancer (Sun et al 2010); gastric cancer (Wu et al 2006); non-small cell lung cancer 
(Sun et al 2006); and melanoma (Loo et al 2012). 

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Most notably, in prostate cancer, expression of B7-H3 is associated with metastatic behavior 
and poor outcome. Utilizing immuno-histochemistry, Roth and colleagues demonstrated that 
B7-H3 is expressed in normal prostate epithelium and is more intensely expressed by 
prostate cancer (Roth et al 2007).  Within their series, virtually all prostate cancer expressed 
B7-H3, however the intensity of expression varied with cancers exhibiting more aggressive 
phenotypes (larger tumors, those with extra-prostatic extension) expressing higher levels of 
the protein.  In addition, marked levels of B7-H3 expression correlated with disease 
progression following surgery.  These results were supported by work from Zang et al. 
which also demonstrated increased expression of B7-H3 in the majority of prostate cancers 
and particularly increased expression in tumors which were non-organ confined at surgery 
(Zang et al 2007).  In their series, strongly positive B7-H3 expression was prognostic of 
clinical failure and death from prostate cancer in univariate models.  Further correlating 
with this data, high B7-H3 expression was also found to be prognostic of disease progression 
following salvage radiation therapy for recurrent prostate cancer after surgery (Parker et al 
2011).  In addition to these studies on primary prostate cancer tissue, B7-H3 protein 
expression has also been explored in metastasis and in prostate cancer treated with 
androgen deprivation.  This study demonstrated B7-H3 expression in bone metastasis with a 
trend towards increased expression upon androgen deprivation (Chavin et al 2009).  
Neoadjuvant androgen deprivation did not appear to alter expression in prostatectomy 
tissue. 
2.2.2 
 Study Agent Enoblituzumab (MGA271) Background 
MGA271 is a humanized monoclonal antibody that binds the B7-H3 immunoligand with high 
affinity (Loo et al 2012). The antibody has been engineered to have enhanced binding to the 
activating Fc R, CD16A, and especially the low affinity allele of CD16A, CD16A-158F. Since 
most patients carry the low-affinity allele of CD16A, the enhanced binding of the Fc-
optimized version is expected to impart binding improvement that benefits the whole 
patient population, not just those patients who are homozygous for the high-binding allele of 
CD16A (valine/valine (V/V) genotype, approximately 15% of the population). MGA271 also 
exhibits reduced binding to the low-affinity inhibitory receptor, CD32B. 
Antibody dependent cellular cytotoxicity (ADCC) has been shown to be an important 
mechanism of action for several monoclonal antibodies including rituximab (Clynes et al 
2000, Weng et al 2003) and trastuzumab (Clynes et al 2000, Musolino et al 2008) and is 
likely an important mechanism of action for MGA271. 
The ability of MGA271 (or RES242 [MGA271 with a wild-type Fc]) to mediate ADCC activity 
was evaluated across multiple cancer types expressing varying levels of B7-H3 as 
determined by flow cytometry. The cancer types tested included: melanoma (A375, UACC-
62), lung cancer (SK-MES-1, A549), prostate cancer (LnCAP), breast cancer (JIMT-1, MDA-
MB-468), bladder cancer (SW780, HT-1197), and renal cancer (ACHN) cell lines.  
MGA271-mediated ADCC activity against all tumor lines that expressed B7-H3 at detectable 
levels. Furthermore, MGA271 showed enhanced ADCC potency compared to the related 
version of the antibody with wild type Fc domains, chBRCA84D or RES240, against all the 
tumor cell lines examined (see Figure 2). Consistent with the studies described above, the 
greatest enhancement in ADCC activity against the B7-H3 expressing prostate cancer cell 
line LnCAP was observed with effector populations obtained from individuals homozygous 
for the weak binding allele of CD16A (phenylalanine/phenylalanine [F/F]). In contrast, 
MGA271 did not mediate ADCC against Raji B-cell lymphoma cells, which do not express 
detectable cell surface B7-H3. 

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Figure 2  
MGA271 (RES242) Mediates ADCC Activity Across a Spectrum of Cancer Types 
 
 
The ability of MGA271 to mediate ADCC was evaluated on B7-H3 positive melanoma (A&B), lung (C&D), 
prostate (E&F), breast (G&H), bladder (I&J), and renal cancer (K) cell lines, as well as the B7-H3 negative Raji 
B cell lymphoma line (L). MGA271 activity was compared to the indicated control molecules: humanized 
BRCA84D (hBRCA84D); chimeric BRCA84D (chBRCA84D), and mouse BRCA84D (mBRCA84D). Resting 
human PBMC from independent healthy donor were utilized and the effector cell to target cell (E:T) ratio is 
UACC-62
E:T=30:1; D#48332 (F/F)
10-3
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
RES240
RES242
mBRCA84D
Concentration (ng/mL)
% Cytotoxicity
SK-MES-1
E:T=25:1; D#46853 (F/V)
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
RES242
RES240
chBRCA84D
Concentration (ng/mL)
% Cytotoxicity
A375
E:T=30:1; D#54070 (F/F)
10-3
10-2
10-1
100
101
102
103
-10
0
10
20
30
40
50
chBRCA84D
RES242
Concentration (ng/mL)
% Cytotoxicity
A549
E:T=25:1; D#46853 (F/V)
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
RES242
RES240
chBRCA84D
Concentration (ng/mL)
% Cytotoxicity
LNCap
E:T=25:1 D#46853 (F/V)
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
70
80
RES242
RES240
chBRCA84D
Concentration (ng/mL)
% Cytotoxicity
LNCap
E:T=25:1 D#50401 (F/F)
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
70
80
RES242
RES240
chBRCA84D
Concentration (ng/mL)
Cytotoxicity (%)
JIMT-1
E:T=30:1; D#54070 (F/F)
10-3
10-2
10-1
100
101
102
103
-10
0
10
20
30
40
50
60
70
80
chBRCA84D
RES242
Concentration (ng/mL)
% Cytotoxicity
MDA-MB-468
E:T=30:1  D#31936  (F/F)
10-3
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
chBRCA84D
RES242
Concentration (ng/mL)
Cytotoxicity (%)
SW780
E:T=30:1  D#51140 (F/V)
10-3
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
ChBRCA84D
RES242
Concentration (ng/mL)
Cytotoxicity (%)
HT-1197
E:T=30:1 D#49480 (F/F)
10-3
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
70
80
RES240
RES242
Concentration (ng/mL)
% Cytotoxicity
ACHN
E:T=30:1  D#31936  (F/F)
10-3
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
60
chBRCA84D
RES242
Concentration (ng/mL)
Cytotoxicity (%)
Raji (B7-H3 negative)
E:T = 30:1 D#53560 (F/F)
10-2
10-1
100
101
102
103
104
-10
0
10
20
30
40
50
RES242
chBRCA84D
Rituximab
Concentration (ng/mL)
Cytotoxicity (%)
A.
D.
E.
B.
G.
J.
K.
H.
F.
C.
L.
I.

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indicated in each panel. The percent cytotoxicity, as determined by lactate dehydrogenase (LDH) release, was 
calculated. 
 
 
A series of in vivo xenograft tumor efficacy studies (RR-RND-MGA271-10-1003) were 
conducted to identify tumor cell lines that are sensitive to MGA271 as a single agent, 
establish dose response profiles for the antitumor activity of MGA271, and identify cancer 
types that exhibit sensitivity to MGA271. Weekly administration of MGA271 resulted in 
significant inhibition of growth of a variety of human tumor xenografts representing bladder, 
gastric, lung, melanoma, prostate, and kidney cancer. MGA271 exhibited antitumor activity 
when administered approximately 1 week after tumor cell implantation or after tumors 
were allowed to become fully established (approximately 3 weeks after implantation when 
tumors were ~300 mm3 in volume).  See MGA271 Investigator’s Brochure for additional 
details. 
2.2.3 
Safety of MGA271 
 
2.2.3.1 Nonclinical Data 
A repeat dose Good Laboratory Practice (GLP) toxicology study was conducted in 
cynomolgus monkeys to determine the potential toxicity and toxicokinetics of MGA271 
when administered weekly for 4 weeks via intravenous (IV) infusion at doses of 1, 10, 30, or 
150 mg/kg and to evaluate recovery from any effects of the MGA271 over a dose-free period 
of at least 8 weeks. In this study, MGA271 was well tolerated at all dose levels evaluated. 
There were no test article-related mortalities and no test article-related changes in clinical 
observations, food consumption, body weight, clinical pathology parameters, gross 
pathology, and organ weights. The no observed adverse effect level (NOAEL) was considered 
to be 150 mg/kg. The detailed report of pathology, laboratory and IHC findings in the 
cynomolgus monkeys from the repeat-dose GLP toxicology study can be found in the IND 
111005 - IB Version 7.  
In IHC studies, MGA271 was shown to recognize epithelial elements in the normal human 
adrenal cortex, and in tissue distribution studies MGA271 was found to distribute to the 
adrenal cortex in cynomolgus monkeys treated with a 150 mg/kg dose. However, no changes 
in hormone parameters were observed in cynomolgus monkeys treated with MGA271. 
 
2.2.3.2 Clinical Trial Experience 
A total of 160 adult patients have received MGA271 at doses up to 15 mg/kg, the maximum 
dose given in this study. One-hundred and forty-six of these patients received MGA271 in 
which MGA271 was given alone (no other chemotherapy was administered with MGA271). 
In other studies, 14 patients received MGA271 in combination with another drug for cancer 
treatment.  To date, no person under the age of 18 has been treated with MGA271. 
So far, the most important safety risk that has been identified with MGA271 is infusion-
related reaction (including reactions known as cytokine release syndrome [CRS]). Infusion-
related reactions are effects to a drug that may occur during or shortly after an infusion. 
Signs and symptoms of an infusion-related reaction may include fever, chills, nausea, 
vomiting, headache, muscle stiffness, rash, itching, low blood pressure, and difficulty 
breathing. Infusion-related reactions can be life threatening and, in rare cases, may cause 
death. Infusion related-reactions have occurred in a total of 37% (about 4 in 10) patients 

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receiving treatment with MGA271. Most of the infusion-related reactions observed in 
patients receiving MGA271 have been mild to moderate in severity. However, six patients 
receiving MGA271 (< 4% of patients) have had serious or severe infusion-related reactions. 
These patients, some of whom were hospitalized for these reactions, recovered after 
receiving treatment with steroids, antihistamines, intravenous fluids, and other medications. 
One patient was discontinued from the study after experiencing a moderate infusion 
reaction. 
The following were the most common side effects that were considered related to MGA271 
administration and were seen in at least 1 of 10 participants. These side effects have been 
generally mild or moderate. 
• 
Infusion-related reactions (including CRS) (37%)  
• 
Fatigue (32%) 
• 
Nausea (18%) 
• 
Chills (14%) 
• 
Vomiting (13%) 
 
A total of 18 patients (11% or 1 in 10 patients) have experienced serious or severe side 
effects that were considered related to MGA271. Serious or severe side effects that occurred 
in 3 or more patients were infusion related reactions (6 patients, described above) and 
hyponatremia (which occurred in 3 patients).  
There have not been any deaths considered related to the use of MGA271.  
 
2.3 
Rationale 
2.3.1 
Rationale for conducting the study 
Prostate cancer remains the second most common cause of cancer related death in males, 
killing one in every 36 American men.  While advances have been made in early detection 
and local treatment, few treatments have been able to dramatically alter the course of 
disease once it progresses to subclinical or clinical metastases.  In that setting, androgen 
deprivation therapy is considered frontline but, while many patients will experience initial 
tumor regression, their prostate cancer inevitably develops a castrate resistant phenotype.  
Recent advances in our understanding and ability to manipulate the immune system have 
resulted in a sea of change in the treatment of aggressive malignancies.  One promising 
approach to metastatic disease involves treatments that use the immune system to target 
and destroy tumor cells. Because an anti-tumor T cell response has the ability to dynamically 
evolve, immunotherapy can potentially overcome the genetic diversity of aggressive and 
advanced cancers.  Moreover, because the immune system develops memory, anti-tumor 
immune responses can be potentially long-lived, and long-lived responses have been 
reported in patients with melanoma, kidney cancer and bladder cancer.  Those recent data 
mostly involve immune checkpoint blockade using anti-CTLA-4 or anti-PD1/PDL1; but in 
prostate cancer those therapies have yielded little in the way of objective responses, 
suggesting the need for alternative immunological approaches. 
B7-H3 is part of the B7 superfamily which includes B7-H1 (PD-L1) and B7-DC (PD-L2).  
Although a number of studies document a role for B7-H3 in modulating the immune 
response, its regulation and mechanism of action are not completely clear, with literature 

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demonstrating both T-cell stimulatory and inhibitory effects.  In addition, tumor cell 
expression of B7-H3 has been associated with an autonomous proliferative and migratory 
function.  Perhaps most relevant, multiple reports (as well as our unpublished data) support 
a correlation between B7-H3 expression and adverse pathology and clinical outcome in men 
with prostate cancer.  Using a large series of surgical specimens in a cohort of men 
uncontaminated by hormonal therapy, we found that B7-H3 expression correlates with stage 
and is associated with biochemical and clinical progression following treatment.  In addition, 
B7-H3 levels remain high in the presence of androgen deprivation.  These studies suggest a 
potential role for B7-H3 in prostate cancer progression and support its use as therapeutic 
target in both the hormone naïve and castrate resistant state.  Here we propose a 
neoadjuvant study to determine the anti-tumor, immunological and biological effects of B7-
H3 inhibition in men with high-risk prostate cancer.  
We aim (1) to investigate whether inhibition of B7-H3 via administration of MGA271 is safe 
and feasible in the neoadjuvant setting; (2) to determine whether MGA271 produces anti-
tumor responses by evaluating tumor cell apoptosis in harvested prostate glands; and (3) to 
determine whether MGA271  triggers an immune response in men with localized prostate 
cancer by evaluating T-cell infiltration in harvested prostate glands. We hypothesize that 
neoadjuvant MGA271 will be feasible and safe, and will produce measurable antitumor 
immune responses. 
If this study shows significant tumor cell apoptosis and enhancement of antitumor immunity 
with MGA271, and administration of the study drug is feasible and safe, then future studies 
would aim to use MGA271 in both the adjuvant and the salvage settings. For example, a trial 
could be designed to assess the efficacy of MGA271 given before and after radical 
prostatectomy, using PSA recurrence as the primary endpoint. Alternatively, a trial of 
MGA271 for patients with PSA recurrence could be designed, with metastatic progression as 
the primary endpoint. 
2.3.2 
Rationale for dosage selection 
In the CP-MGA271-01 Phase I study, dose escalation was carried out from 0.01 mg/kg to 15 
mg/kg without a DLT observed at any dose level. As 15 mg/kg was the highest protocol 
specified dose, 15 mg/kg was determined as the maximum administered dose (MAD), and 
that dose carried into the expansion phase of that study. The safety profile of MGA271 based 
on a total of 51 patients exposed to MGA271 demonstrated that the majority of AEs were 
mild (CTCAE Grade 1 or 2), with toxicities manageable by standard medical therapy. One 
patient has discontinued MGA271 for a drug related toxicity that was considered to be a 
drug-related SAE. (See Investigator’s Brochure version 8 for a more detailed description 
of the safety profile from Study CP-MGA271-01). 
Preliminary PK modeling indicates that MGA271 administered at doses below 5 mg/kg IV on 
a weekly schedule follows a target-mediated drug disposition model. At doses above 
5 mg/kg, exposure increased approximately linearly with the dose (See Investigator’s 
Brochure version 5, Table 9). At doses above 5 mg/kg, linear two-compartment model 
with clearance, CL=0.201 L/day; central volume, Vc=3.22 L; inter-compartment clearance, 
Q=0.700 L/day; and peripheral volume, Vp= 3.68 L, provided adequate description of the 
observed data. The distribution half-life (i.e., the initial rapid distribution to tissues [T1/2α]) 
and the terminal half-life [T1/2β] were estimated at 1.6 days and 25 days, respectively. 

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2.3.3 
Rationale for immunobiologic endpoints 
The primary efficacy goal of this study is to assess direct antitumor effects in prostate 
tumors after administering the protocol therapy consistent with the agent’s proposed 
mechanism of action (MOA), antibody-dependent cellular cytotoxicity (ADCC).  To this end, 
we will measure tumor apoptosis and proliferation using validated markers such as 
activated caspase 3 (Marcelli et al 2000) and Ki-67 (Rubin et al 2002). These will be assessed 
by immunohistochemical staining of formalin-fixed tissue samples. Ki-67 is a nuclear antigen 
that is found in proliferating cells, whose expression correlates with the degree of apoptosis 
and cellular turnover in prostate cancer (Berges et al 1995). Apoptotic cells will also be 
identified histologically and quantified by the method of terminal deoxynucleotidyl 
transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL 
assay) (Furuya et al 1995).  
In an exploratory fashion, we will also assess B7-H3 expression in pre and post treatment 
tumor tissue and correlate with tumor cell apoptosis and time to PSA-recurrence. 
We will also assess the degree of immune infiltration into the prostate after administering 
the protocol therapy. In studies using the ProHA × TRAMP mouse model, the primary 
endpoint was hemagglutinin (HA)-specific CD8+ T cell responses in harvested prostate 
glands (Wada et al 2009). Our previous studies have shown that the mean staining 
percentage for CD8+ T cells in human prostate tumor tissue is 0.42% (standard deviation 
0.36%, interquartile range 0.07%–0.71%). In the present study, CD8+ T cell density will 
serve as a surrogate measure of prostate-/prostate cancer-specific T cell responses.  
We will also evaluate the proportion of patients achieving a pathological complete response 
(pCR).  
3. 
PATIENT SELECTION 
3.1 
Target Population 
Subjects will include men with multifocal, Gleason 7 or greater, clinically localized prostate 
cancer for whom the decision has been made to perform radical prostatectomy at Johns Hopkins 
Hospital. Subjects will be identified and recruited through the Outpatient Clinic of the Department of 
Urology and from the Multidisciplinary Prostate Cancer Clinic. 
3.2 
Inclusion Criteria  
To be eligible for this study, patients must meet all of the following criteria: 
• 
Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c–T3b, N0, M0) 
without involvement of lymph nodes, bone, or visceral organs 
• 
Initial prostate biopsy is available for central pathologic review, and is confirmed to show at 
least 2 positive cores and a Gleason sum of ≥7 
• 
Radical prostatectomy has been scheduled at Johns Hopkins Hospital 
• 
Age ≥18 years 
• 
ECOG performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A) 
• 
Adequate bone marrow, hepatic, and renal function: 
o 
WBC >3,000 cells/mm3 
o 
ANC >1,500 cells/mm3 

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o 
Hemoglobin >9.0 g/dL 
o 
Platelet count >100,000 cells/mm3 
o 
Serum creatinine <1.5 × upper limit of normal (ULN) 
o 
Serum bilirubin <1.5 × ULN 
o 
ALT <3 × ULN 
o 
AST <3 × ULN 
o 
Alkaline phosphatase <3 × ULN 
• 
The etiology of abnormal bilirubin and transaminase levels should be evaluated prior to 
study entry. 
• 
Willingness to provide written informed consent and HIPAA authorization for the release of 
personal health information, and the ability to comply with the study requirements (note: 
HIPAA authorization will be included in the informed consent) 
• 
Willingness to use barrier contraception from the time of first dose of MGA271 until the time 
of prostatectomy. 
3.3 
Exclusion Criteria 
To be eligible for this study, patients should not meet any of the following criteria: 
• 
Presence of known lymph node involvement or distant metastases 
• 
Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, 
and neuroendocrine tumors 
• 
Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate 
cancer 
• 
Prior immunotherapy/vaccine therapy for prostate cancer 
• 
Prior use of experimental agents for prostate cancer 
• 
Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors 
• 
Current use of systemic corticosteroids or use of systemic corticosteroids within 4 weeks of 
enrollment (inhaled corticosteroids for asthma or COPD are permitted as are other non-
systemic steroids such as topical corticosteroids) 
• 
History or presence of autoimmune disease requiring systemic immunosuppression 
(including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, 
vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren 
syndrome, and sarcoidosis) 
• 
History of malignancy within the last 3 years, with the exception of non-melanoma skin 
cancers and superficial bladder cancer 
• 
Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric 
illnesses that would make the patient a poor study candidate 
• 
Known prior or current history of HIV and/or hepatitis B/C  
3.4 
Inclusion of Minorities 
Men of all races and ethnic groups will be considered for study participation. Candidates must 
conform to all eligibility criteria to be accepted into the study. Minority patients who meet entry 
criteria will be actively recruited, although the trial is not designed to measure differences in 

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outcomes between ethnic groups. The estimated breakdown of the target population by race and 
ethnicity is: 80% white/Caucasian, 15% black/African American, and 5% comprised of other ethnic 
minorities. 
3.5 
Prohibited Concomitant Medications 
Concurrent use of other anticancer agents or therapies including other experimental treatments is 
not permitted. Patients may not currently be taking any other form of androgen deprivation therapy, 
antiandrogens, 5-reductase inhibitors, chemotherapy, radiation therapy, biologic therapy, 
immunosuppressive medications, or systemic corticosteroids. 
Within 30 days of administration of study drug, patients should not receive vaccines including but 
not limited to the live rotavirus vaccine, the live BCG (bacillus Calmette-Guerin) vaccine, the live 
influenza vaccine, the live measles vaccine, the live mumps vaccine, the live poliovirus vaccine, the 
live rubella vaccine, the smallpox vaccine, the typhoid vaccine, the varicella vaccine, and the yellow 
fever vaccine. 
Because of the potential for unknown drug-drug interactions, concurrent use of all other agents, 
over-the-counter medications, herbal remedies, vitamins/minerals, and alternative therapies must 
be documented on the case report form (CRF).
4. 
REGISTRATION AND ENROLLMENT PLAN 
4.1 
Registration Procedure 
Patients who are considered candidates for the study will first be evaluated for eligibility by one of 
the principal investigators, co-investigators, or the research nurse. After screening for eligibility, 
patients who are eligible to participate in the trial must be registered with the Sidney Kimmel 
Comprehensive Cancer Center (SKCCC) according to the instructions below. A record of patients who 
fail to meet entry criteria (i.e., screen failures) will also be maintained. Registration must be 
completed before beginning any study-related activities. 
To initiate registration at SKCCC, study personnel should forward copies of the signed informed 
consent form (with embedded research authorization/HIPAA form), the institutional registration 
form, plus any required pathology information/laboratory tests to the project manager by fax or 
email. Once eligibility is confirmed, each subject will be assigned a unique patient study identification 
number. Treatment must not commence until the patient has received his identification number. 
Prior to protocol enrollment and initiation of treatment, subjects must sign and date an IRB-
approved consent form. Authorized study personnel should fully explain the scope of the study to 
each patient before obtaining informed consent. Patients should be advised of any known risks 
inherent in the planned treatments/procedures, any alternative treatment options, their right to 
withdraw from the study at any time and for any reason, and their right to privacy. When obtaining 
informed consent, study personnel should: first, confirm that the patient has received and has had 
time to read the informed consent form (including the research authorization/HIPAA form); next, 
confirm eligibility as defined in Sections 3.2 and 3.3 (inclusion and exclusion criteria); and finally, 
obtain dated and signed informed consent. A copy of the signed informed consent should be supplied 
to the project manager. 
To register a patient, the following documents must be completed and faxed 410-614-7273 or 
emailed (thefka1@jhmi.edu) to the study coordinator (Taylor Hefka): 
• 
signed patient consent form 
• 
institutional registration form 

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• 
copies of the prostate cancer pathology report and baseline laboratory studies including CBC 
with differential, liver and kidney function tests. Other materials may also be sent if 
considered pertinent for confirming patient eligibility. 
The principal investigator and/or other authorized study personnel will then review these 
documents to confirm eligibility. To complete the registration process, the project manager will 
assign a patient study number (i.e., protocol patient number). This number is unique to the patient 
and must be written on all data and correspondence for the patient. The project manager will also 
register the patient with SKCCC’s Clinical Research Office (CRO). 
4.2 
Expected Enrollment 
A total of 32 patients will be included in this study. The first patients are expected to be enrolled in 
February 2016, once the protocol has been approved by the IRB. With an estimated enrollment rate 
of 3 patients per month, accrual is expected to be completed in 5-6 months. 
4.3 
Study Centers 
This is a single-institution study that will be conducted only at Johns Hopkins through a collaboration 
between the Brady Urological Institute and the Sidney Kimmel Comprehensive Cancer Center. 
4.4 
Recruitment 
Subjects will be recruited from the outpatient facilities of the Brady Urological Institute, and from the 
outpatient Multidisciplinary Prostate Cancer Clinic of the SKCCC. Patients will not receive payment or 
reimbursement for participation. Every effort will be made to include patients of racial and ethnic 
minorities who fulfill the eligibility criteria.
5. 
STUDY PLAN 
5.1 
Overview and Schema 
This is a single-center, single arm, open-label pilot study evaluating the safety, anti-tumor effect, and 
immunogenicity of neoadjuvant MGA271 given prior to radical prostatectomy in men with high-risk 
localized prostate cancer. Patients will be recruited from the outpatient Urology clinic. Eligible 
patients will receive MGA271 at a dose of 15mg/kg IV given weekly for 6 doses beginning 50 days 
prior to radical prostatectomy. 14 days after the last dose of MGA271, prostate glands will be 
harvested at the time of radical prostatectomy, and prostate tissue will be examined for the 
secondary endpoints.  Follow-up evaluation for adverse events will occur 30 days and 90 days after 
surgery. Patients will then be followed by their urologists according to standard institutional 
practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) 
months during years 2-3. 
 
 
                             Study Schema: 

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. 
 
 
 

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Table 1   STUDY CALENDAR 
 
Every effort should be made to keep visits, tests, and procedures on schedule. Acceptable deviations 
are listed below. 
 
 
Screening 
Evaluation a 
Treatment 
Days (1, 8, 15, 
22, 29, 36) 
(+/- 1 day) 
Radical 
Prostatectomy, 
Day 50 (+/- 3 
days) 
Follow-up, 30, and 
90 Days Post-op 
(+/- 1 wk) h,i 
Informed consent 
X 
 
 
 
Medical history 
X 
 
X 
 
Review of medications 
X 
X 
X 
X 
Physical assessment 
X 
X 
X 
 
Vital signs 
X 
X 
X 
 
Height and weight 
X 
X 
X 
 
Performance status 
X 
X 
X 
X 
CT and bone scan b 
(X) 
 
 
 
Hematology labs c 
X 
X 
X 
X 
Chemistry labs d 
X 
X 
X 
X 
Serum PSA e 
X e 
 
X 
 X e 
MGA271 dose  
 
X 
 
 
Toxicity assessment 
         X------------------------------------------------------------------X 
Surgical specimen f 
 
 
X 
 
Pathologic review g 
X 
 
X 
 
Sera for Immunoassays l 
X 
 
X 
X 
Whole Blood (100 mL) for 
PBLs collection 
 
Xk 
 
Xk 
B7-H3 IHC 
Xg 
 
Xf 
 
Fc Receptor Genotyping 
 
Xj 
 
 
TCR Repertoire (8.5 mL 
PaxGene DNA) 
 
Xj 
Xj 
Xj 
a: 
The screening (pre-treatment) evaluation should be conducted within 3 weeks (±4 days) of starting protocol therapy. 
b: 
Staging CT (if allergic to CT scan contrast, obtain MRI with contrast) and bone scans should only be performed if 
clinically indicated, and are not mandatory. 
c: 
Hematology laboratories include hemoglobin, hematocrit, white blood cell count with differential (including absolute 
eosinophil count), and platelets. In addition, prothrombin time (PT/INR) and activated partial thromboplastin time 
(APTT) should be checked as clinically indicated. These labs should be collected prior to treatment. 
d: 
Chemistry laboratories include sodium, potassium, chloride, bicarbonate, urea nitrogen, creatinine, glucose, calcium, 
albumin, total protein, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase, amylase, and lipase. 
e: 
Serum PSA should be obtained pre-treatment (at least 30 days from biopsy) and on the day of surgery, and every 3 
months (±1 mo) for post-op year one then every 6 months (±2 mo) for post-op years two and three. 
f: 
Harvested prostate gland to be evaluated for tumor apoptosis, CD8+ T cell infiltration, as well as other secondary and 
exploratory endpoints. 
g: 
Archival prostate core biopsies to be centrally reviewed at baseline prior to study entry; radical prostatectomy 
specimens to be processed at Johns Hopkins according to standard procedures.  Archival tissue for B7-H3 IHC testing 
to be sent to MacroGenics. 
h: 
The post-operative evaluations (30 and 90 days after prostatectomy) may take place over the telephone or in person, 
but patients are required to have hematology and chemistry labs collected at this time-point for safety purposes. 
i: 
In addition, PSA should be measured every 3 months (±1 month) in the first year after prostatectomy, and every 6 

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months (±2 months) in the second and third years after prostatectomy. 
j: 
Fc Receptor Genotyping and TCR Repertoire is collected prior to treatment in one 8.5 mL PaxGene DNA collection 
tube.  TCR Repertoire is collected on the day of surgery, and 30 and 90 days post-op. 
k: 
PBLs should be collected on treatment day 1 (pre-treatment), treatment day 36 (post-treatment), and follow-up day 
30 (see Appendix F) 
l: 
See Appendix F for specimen collection instructions for Sera for immunoassays. 

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5.2 
Screening/Pretreatment Evaluation  
Before initiating any screening activities, the scope of the study should be explained to each patient. 
Patients should be advised of any known risks inherent in the planned procedures, any alternative 
treatment options, their right to withdraw from the study at any time and for any reason, and their 
right to privacy. After this explanation, patients should be asked to sign and date an IRB-approved 
informed consent form that meets the requirements of the Code of Federal Regulations (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50). 
The pretreatment/screening visit will determine patient eligibility according to the inclusion and 
exclusion criteria. All subjects must undergo a number of baseline evaluations as part of this 
screening visit, as detailed below. All of these evaluations should be conducted within 21 ± 4 days of 
starting the protocol. This information is also summarized in the Study Calendar (Table 1). 
• 
informed consent 
• 
demographic information 
• 
medical history, including review of systems 
• 
performance status, using ECOG or Karnofsky scales (Appendix A) 
• 
physical assessment 
• 
vital signs: temperature, pulse, sitting blood pressure, respiratory rate 
• 
height and weight 
• 
current medication list, including drug allergies/adverse events 
• 
hematological laboratories (hemoglobin, hematocrit, white blood cell count with differential 
[including absolute eosinophil count], platelets); coagulation profile (INR, aPTT) if clinically 
indicated 
• 
serum chemistry profile (sodium, potassium, chloride, bicarbonate, urea, creatinine, glucose, 
calcium, albumin, total protein, bilirubin, ALT, AST, alkaline phosphatase, amylase, lipase) 
• 
serum PSA level 
• 
CT (If allergic to CT scan contrast, obtain MRI with contrast) and/or bone scan, only if 
clinically indicated (not mandatory) 
• 
central pathologic review of prostate core biopsies 
• 
Sera for immunoassays  
After all relevant screening information is documented, registration should be finalized and 
appropriate documents (i.e., signed informed consent, supporting source documentation for 
eligibility) should be faxed or emailed to the program manager. 
Information on patients who do not meet eligibility criteria to participate in this study (i.e., screening 
failures) should also be captured at the pretreatment visit.
5.3 
Treatment Visits  
Treatment initiation with MGA271 may begin at least 1 week after diagnostic biopsy granted the 
patient does not have any complications from biopsy. The following must be performed on treatment 
days (days 1, 8, 15, 22, 29, 36) (±1 day) with administration of MGA271.  
• 
performance status 
• 
review of medication list 

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• 
review of toxicity/adverse events 
• 
height/weight 
• 
vital signs (before, halfway through, and after 2-hr infusion) 
• 
physical exam (focused) 
• 
hematological laboratories and serum chemistry profile 
• 
PBMC collection for TCR repertoire 
• 
Whole blood for PBLs (treatment days 1 and 36 only) 
• 
Whole blood for Fc receptor genotyping Day 1 only 
• 
Administration of MGA271 15mg/kg IV (see section 6.3 Study Drug Administration) 
5.4 
Radical Prostatectomy 
The following must be performed on the day of radical prostatectomy, which itself should occur 50 
(±3) days after the administration of the first dose of MGA271. 
• 
medical history 
• 
performance status 
• 
physical assessment, including vital signs 
• 
review of medication list 
• 
review of toxicity/adverse events 
• 
hematological laboratories and serum chemistry profile 
• 
serum PSA 
• 
collection of prostatectomy tissue for analysis of study endpoints 
• 
pathological processing of prostatectomy specimen according to standard procedures 
• 
Sera for immunoassays  
• 
PBMC collection for TCR Repertoire 
5.5 
Follow-Up Evaluations 
Follow-up visit scheduled for 30 days and 90 days after radical prostatectomy may occur in the 
outpatient clinic. Required evaluations during this follow-up visits are listed below. Patients should 
then continue to be followed by their treating urologist according to standard institutional practices. 
• 
performance status 
• 
review of medication list 
• 
review of toxicity/adverse events 
• 
hematological laboratories and serum chemistry profile 
• 
Serum PSA at post-operative day 90 
• 
Sera for immunoassays  
• 
PBMC collection for TCR Repertoire 
• 
Whole blood for PBLs (post-op day 30 only) 
 

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Patients withdrawing from the study early because of adverse events should be followed until the 
adverse event has either resolved or stabilized. Reasons for premature withdrawal should be 
determined and documented. 
In addition, patients will be required to have a structured assessment of post-operative PSA 
measurements for 3 years. In the first year after prostatectomy, PSA will be measured every 3 
months (±1 mo). In the second and third years after prostatectomy, PSA will be measured every 6 
months (±2 mo). These PSA measurements may be obtained outside of Johns Hopkins, but the results 
need to be made available to the study team. 
5.6 
Duration of Therapy 
Participation in this study will be terminated for any of the following reasons listed below: 
• 
the patient decides to withdraw from the study (withdrawal of consent) due to unacceptable 
toxicities or for any other reason 
• 
the patient completes all of the protocol procedures and follow-up requirements 
• 
there are adverse events that, in the judgment of the investigator, may cause severe or 
permanent injury or are incompatible with continuation on study 
• 
there are major violations to the study protocol or the patient is noncompliant with 
treatments, as judged by the investigator 
• 
the patient experiences concurrent illness or a change in his condition that, in the judgment 
of the investigator, renders him unacceptable for further treatment on study 
• 
the patient dies 
• 
the patient is lost to follow-up 
• 
the study is prematurely terminated for safety or feasibility concerns or other reasons 
Patients should be removed from the study when any of the above criteria are met. Because an 
excessive rate of withdrawals can render the study uninterpretable, unnecessary withdrawal of 
patients should be avoided if possible. When a patient leaves the study early, the investigator should 
make every effort to contact the patient and to perform the final follow-up evaluation (even by 
telephone interview). The reason for removal of a patient from the study, and the date of removal, 
must be appropriately documented. 
Patients will be replaced if they are removed from the study after signing the informed consent but 
before undergoing radical prostatectomy. Patients receiving at least one dose of the study drug will 
be included in safety analyses, and those also undergoing prostatectomy will be used for the efficacy 
analyses. 
6. 
STUDY TREATMENT 
6.1 
Description of Study Drug and Supplies 
The MGA271 drug product is a sterile, preservative-free, clear to slightly opalescent, colorless to pale 
yellow or pale brown solution supplied at a protein concentration of 25 mg/mL in a single-use 20 mL 
vial containing 17 mL (425 mg) MGA271. The product is formulated in 0.95 mg/mL sodium acetate 
trihydrate, 0.18 mg/mL glacial acetic acid, 90 mg/mL sucrose, 0.1 mg/mL polysorbate 80 and Water 
for Injection, United States Pharmacopeia (USP) at a pH of 5.1. 

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MGA271 is supplied as a sterile aqueous solution packaged in a USP and Ph. Eur. conforming Type I 
borosilicate, 20 mL clear glass vial with a 20 mm FluroTec-coated 4432/50 gray butyl rubber serum 
stopper. The vial is sealed with a 20 mm TruEdge aluminum closure with a plastic overseal. MGA271 
will be administered by IV infusion over 120 minutes. A sterile, non-pyrogenic, low-protein binding 
polyethersulfone (PES) 0.2 micron in-line filter administration set must be used for IV administration 
of MGA271.  MGA271 must not be administered as an IV push or bolus. 
Under no circumstances is the Investigator allowed to release these clinical supplies for use by 
another physician not named on Form FDA 1572 or to administer study drug to a patient who is not 
enrolled in this study. Study drug must be dispensed at an institution specified on Form FDA 1572. 
Requests to MacroGenics, Inc for additional study drug should be made at least 2 weeks in advance. 
6.2 
Drug Preparation 
6.2.1 
General Guidelines and Precautions 
The calculated dose will be administered based on the patient’s actual weight at Day 1. 
Significant (≥ 10%) change in body weight from baseline should prompt recalculation of 
dose.  
Infusion or allergic reactions may occur with the infusion of monoclonal antibodies and 
other protein-based therapeutics. Precautions for anaphylaxis should be observed during 
MGA271 administration. Supportive measures may include, but are not limited to: 
epinephrine, antihistamines, corticosteroids, IV fluids, vasopressors, oxygen, 
bronchodilators, diphenhydramine, and acetaminophen. Please refer to Section 6.4.4 for 
specific guidelines regarding the management of infusion reactions. Supportive care 
measures consistent with optimal patient care will be provided throughout the study 
according to institutional standards. 
6.2.2 
MGA271 
• 
Inspect parenteral drug products visually for particulate matter and discoloration prior to 
administration. Discard vial if solution is cloudy, there is pronounced discoloration 
(solution may have pale-yellow color), or there is foreign particulate matter. 
• 
The desired amount of MGA271 should be withdrawn from the vial(s) and diluted to the 
appropriate final concentration with 0.9% Sodium Chloride Injection USP, according to the 
instructions provided in the Pharmacy Manual.  
• 
The infusion bag containing MGA271 should be gently inverted to mix the solution. THE 
BAG MUST NOT BE SHAKEN; excessive agitation may cause aggregate formation.  
• 
Discard partially used vials of MGA271 
• 
Administration of study drug should begin immediately after preparation but no later than 
6 hours after preparation (see Pharmacy Manual). If there is a delay in administration of 
study drug such that it will not be administered on the day of preparation, the Medical 
Monitor should be notified immediately. Instructions on how to proceed will be provided. 

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6.2.3 
Placebo or Control 
There will be neither placebo nor active control drug for this study. 
6.3 
Study Drug Administration 
• 
Do not mix MGA271 with, or administer as an infusion with, other medicinal products. 
• 
Administer the diluted solution over 120 minutes through an intravenous line using an infusion 
pump. A sterile, non-pyrogenic, low-protein binding polyethersulfone (PES) 0.2 micron in-line 
filter administration set must be used for IV administration of MGA271.  
• 
Do not use non-polyolefin IV infusion bags. 
6.4 
Potential Adverse Events and Supportive Care Measures 
6.4.1 
Infusion Related Reactions Including Cytokine Release Syndrome 
MGA271 is an immune modulating agent that may lead to T-cell activation and killing of the 
tumor cell.  Activation of T cells is associated with the production of various cytokines.  
Infusion reactions (including cytokine release syndrome [CRS]) associated with MGA271 
administration should be managed according to the standard practice of medicine. General 
guidelines for the management of such reactions are provided in this section. However, 
severe reactions may require more intensive interventions (e.g., steroids, anti-TNF 
antibodies, and/or IL-6 inhibitors). 
Infusion related-reactions have occurred in a total of 37% (about 4 in 10) patients receiving 
treatment with MGA271. Most of the infusion-related reactions observed in patients 
receiving MGA271 have been mild to moderate in severity. However, six patients receiving 
MGA271 (< 4% of patients) have had serious or severe infusion-related reactions. These 
patients, some of whom were hospitalized for these reactions, recovered after receiving 
treatment with steroids, antihistamines, intravenous fluids, and other medications. One 
patient was discontinued from the study after experiencing a moderate infusion reaction. 
Patients should be monitored closely for CRS symptomology in the infusion clinic for the first 
2 hours after the end of the initial MGA271 infusion and then for 1 hour after the 
remaining infusions. Patients should also be monitored closely for the development of 
other infusion-related reactions during the MGA271 infusion. Medications and supportive 
measures for the treatment of severe hypersensitivity reactions should be available for 
immediate use for an infusion reaction during study drug administration and may include, 
but are not limited to: subcutaneous (SC) epinephrine (0.3 to 0.5 mL of a 1:1000 solution), 
antihistamines (e.g., diphenhydramine 25 to 50 mg IV), corticosteroids (e.g., hydrocortisone 
20-40 mg IV push or equivalent), IV fluids, vasopressors, oxygen, bronchodilators, and 
antipyretics. Resuscitation equipment and other supplies for the emergency management of 
an allergic/toxic reaction must be available. The patient should be treated according to the 
best available local practices and procedures. All supportive measures consistent with 
optimal patient care will be provided throughout the study according to institutional 
standards. 
Should symptoms of fever or chills develop it may be difficult to distinguish among potential 
causes of the symptoms including emerging infection, or infusion reaction. Patients should 
be evaluated carefully for the presence of infection, with the acquisition of cultures and/or 

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implementation of empiric antibiotic therapy as appropriate based on the assessment of the 
Investigator. Please refer to Section 6.4.4 for guidance regarding the management of 
infusion reactions. 
6.4.2 
Grading of Infusion Reactions 
Infusion reactions will be categorized as follows: 
• 
Grade 1:  mild reaction; infusion interruption not indicated, intervention not indicated; 
Note: although interruption in infusion is not indicated, temporary rate reduction 
indicated before resuming original rate, as patient tolerates (see Section 6.4.4); 
• 
Grade 2:  therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment [e.g., antihistamines, non-steroidal anti-inflammatory drugs 
(NSAIDS), narcotics, IV fluids]; prophylactic medications indicated for  24 hours; 
• 
Grade 3:  prolonged (e.g., not rapidly responsive to medication and/or brief interruption 
of infusion); recurrence of symptoms following initial improvement; hospitalization 
indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates); 
• 
Grade 4:  life-threatening consequences; pressor or ventilatory support indicated; 
• 
Grade 5:  death. 
The above grading scale is the CTCAE v 4.03 grading scale for CRS, which is nearly identical 
to the CTCAE v 4.03 grading scale for infusion reaction and allergic reaction, and therefore 
considered appropriate for grading all infusion reactions in this study, irrespective of the 
underlying mechanism of the reaction. The Sponsor’s Medical Monitor or designee should be 
contacted immediately if questions arise concerning the grade of the reaction. 
6.4.3 
Premedications and Prophylaxis 
For MGA271, the following suggested guidelines (which may be modified by the 
investigator) are measures to be followed to avoid potential infusion reactions. 
Prior to first infusion (guidelines to be followed): 
• 
Acetaminophen 650 mg 
• 
Diphenhydramine 50 mg or appropriate dose of equivalent H1 antagonist 
• 
Ranitidine 300 mg or appropriate dose of equivalent H2 antagonist at the discretion 
of the investigator 
• 
Hydrocortisone 20 to 40 mg (dose selected at the discretion of the Investigator) 
Prior to subsequent MGA271 infusion, investigators may use the following premedications 
as considered indicated (suggested guidelines): 
• 
Acetaminophen 650 mg 
• 
Diphenhydramine 50 mg or appropriate dose of equivalent H1 antagonist 
• 
Ranitidine 300 mg or appropriate dose of equivalent H2 antagonist 
• 
Optional hydrocortisone 20 to 40 mg (dose selected at the discretion of the 
Investigator) 

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For subsequent MGA271 doses, patients who had infusion reactions who were not 
adequately or only moderately controlled with acetaminophen, diphenhydramine, or 
ranitidine, IV hydrocortisone at doses of 20-40 mg may be considered. 
6.4.4 
Management of Observed Infusion Reactions 
The following are treatment guidelines for MGA271 (which may be modified as needed by 
the Investigator according to the best practices of medicine) for infusion reactions.  
6.4.4.1 Grade 1: 
• 
Slow the infusion rate by 50%. 
• 
Monitor the patient for worsening of condition. 
• 
Continue rate at 50% reduction and increase dose rate to the original rate by 
doubling the infusion rate after 30 minutes, as tolerated to the initial rate. 
Consideration can be given to beginning all subsequent infusions at 50% rate and 
increasing as tolerated.  
• 
If a patient has an infusion reaction with MGA271, prophylactic preinfusion 
medications should be considered prior to all subsequent MGA271 infusions as 
written below. 
• 
The following prophylactic preinfusion medications are recommended prior to 
future infusions of MGA271 for patients who experience Grade 1 infusion reactions: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen 650 mg at least 30 
minutes before additional study drug administrations. 
6.4.4.2 Grade 2: 
• 
Stop the infusion. 
• 
Administer diphenhydramine hydrochloride 25-50 mg IV, acetaminophen 650 mg 
orally for fever, and oxygen and bronchodilators for mild bronchospasm.  
• 
Resume the infusion at 50% of the prior rate once the infusion reaction has resolved 
or decreased to Grade 1. The rate may then be escalated to the original rate after 30 
minutes, as tolerated. Consideration can be given to beginning all subsequent 
infusions at 50% rate and increasing as tolerated. 
• 
Monitor for worsening condition. If symptoms recur, discontinue the infusion; no 
further study drug will be administered at that visit.  
• 
For patients with Grade 2 infusion reactions despite premedication with 
diphenhydramine and acetaminophen, corticosteroids (hydrocortisone 20-40 mg IV 
or equivalent) should be considered for acute management of the event and should 
be added to the premedication regimen for subsequent dosing of  MGA271.  
6.4.4.3 Grade 3: 
• 
STOP THE INFUSION AND DISCONNECT THE INFUSION TUBING FROM THE 
PATIENT. 
• 
TO AVOID EXACERBATION OF INFUSION REACTION OR CRS: DO NOT FLUSH THE 
TUBING – ASPIRATE RESIDUAL DRUG FROM THE PORT LUMEN 

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• 
Administer diphenhydramine hydrochloride 25-50 mg IV, hydrocortisone 25-
100 mg IV (or equivalent), and other medications/treatment as medically indicated. 
Higher doses of corticosteroids (i.e. methylprednisolone 2 -4 mg/kg IV) may also be 
considered for acute management.  
• 
IV fluids, supplemental oxygen and bronchodilators should be considered as 
appropriate.  
• 
If symptoms have resolved to baseline within 12 hours, a re-challenge may be 
considered at the next scheduled dose, with a 50% reduction of infusion rate. In 
addition, patients should be pre-medicated for this re-challenge and for any 
subsequent doses of MGA271 with the following: diphenhydramine hydrochloride 
25-50 mg IV, oral acetaminophen 625 mg and hydrocortisone 25-100 mg IV. 
Patients who have a Grade 3 infusion reaction that does not resolve within 12 hours 
despite medical management should not receive further MGA271. 
• 
Patients who experience a second Grade 3 infusion reaction at the time of re-
challenge of MGA271 (irrespective of duration of first Grade 3 reaction), will 
permanently discontinue MGA271.  
• 
Patients who experience a Grade 3 infusion reaction despite steroid premedication 
administration should permanently discontinue study drug. 
• 
Report as an Immediately Reportable Event (IRE) within 24 hours. 
• 
Report the event as a SAE, if appropriate. 
6.4.4.4 Grade 4: 
• 
Stop the infusion and disconnect the infusion tubing from the patient.  
• 
TO AVOID EXACERBATION OF INFUSION REACTION OR CRS: DO NOT FLUSH THE 
TUBING. 
• 
Administer diphenhydramine hydrochloride 50 mg IV, methylprednisolone 2-
4 mg/kg IV (or more as considered appropriate), and other medications/treatment 
as medically indicated (e.g., an IL-6 receptor inhibitor or IL-6 inhibitor, an IL-2 
receptor inhibitor, and/or an anti-TNF antibody). 
• 
Give epinephrine or bronchodilators as indicated. 
• 
Support ventilation and blood pressure as indicated. 
• 
Report as an IRE within 24 hours. 
• 
Report the event as an SAE.  
• 
Patients who have a Grade 4 infusion reaction will not receive further MGA271. 
6.4.4.5 Grade 5: 
• 
Report as an IRE within 24 hours. 
• 
Report the event as an SAE. 
All changes in the infusion of MGA271 including interruption of the infusion and its duration 
as well as reductions in infusion rate and duration must be recorded. 

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6.4.5 
Dose Management for Adverse Events considered related to MGA271 
Temporary interruptions of MGA271 may be required in the event of treatment-related 
toxicity. General guidelines for specific toxicity regarding dosing and treatment are provided 
below. All toxicities will be graded according to NCI CTCAE v4.03 (see Section 7.1.2). 
6.4.5.1 Grade 1 or 2 AEs 
Study drug administration may continue despite observation of drug-related low 
grade adverse events (CTCAE grade 1 or 2). If the investigator in his/her medical 
judgment considers that a low grade AE is of clinical significance or inordinately 
prolonged, the Investigator may, at his/her discretion, delay treatment to allow for 
resolution. Necessity to delay for more than two consecutive doses will require the 
patient to permanently discontinue study drug. Study drug should also be 
discontinued for prolonged Grade 2 AEs lasting ≥ 14 days that are at least possibly 
related to study drug. No dose reductions are allowed. 
6.4.5.2 Grade 3 or 4 AEs 
Drug administration should be held upon observation of AEs of ≥ Grade 3 severity to 
enable patient management, monitoring of the resolution of the event, and 
assessment of the relatedness of the event. An AE of ≥ Grade 3 that is considered 
related to MGA271 will result in discontinuation of therapy unless otherwise 
specified in the protocol.  For AEs associated with liver function test abnormalities, 
drug administration should also be discontinued for concomitant ALT >3xULN and 
total bilirubin >2x ULN without an alternative etiology (Hy’s Law).   
6.5 
Concomitant Therapy 
MGA271 is the only cancer drugs to be administered routinely in this study.  No concomitant anti-
cancer therapy will be given.  
All concomitant medications and blood products administered during the patient’s participation in 
the study until the post treatment follow-up visit must be recorded in the source document and on 
the electronic Case Report Form (eCRF). All changes in infusions, including interruptions and their 
duration as well as reductions in rate and duration must be recorded. 
The following rules concerning concurrent treatment(s) will apply in this study: 
Any other anti-neoplastic therapies including but not limited to chemotherapy or other small 
molecules, biologics, or radiotherapy are not allowed. 
• 
Patients may not receive other investigational drugs during the period of study participation. 
• 
Because MGA271 has a mechanism of action dependent upon the engagement of T 
lymphocytes, the use of corticosteroids should be limited to the extent possible.  Chronic 
doses of corticosteroids in excess of 10 mg daily of prednisone or equivalent is prohibited 
other than for the management of drug-related adverse experiences.  Steroids may be 
employed in the treatment of suspected MGA271-associated immune-inflammatory or 
autoimmune AEs in consultation with the Sponsor. 
• 
The use of other immuno-suppressive agents is prohibited, unless they are being used to 
treat an adverse event.  

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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• 
Use of granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating 
factor or other growth factors is prohibited. 
Patients may receive the following concurrent therapy: 
• 
Antiemetics, antidiarrheals, anticholinergics, antispasmodics, antipyretics, antihistamines, 
analgesics, antibiotics and other antimicrobials, histamine receptor antagonists or proton 
pump inhibitors, and other medications intended to treat symptoms or signs of disease. 
• 
Transfusions such as red blood cells and platelets are permitted to treat symptoms or signs 
of anemia or thrombocytopenia and should be documented on the concomitant medication 
form. 
6.6 
Restrictions 
6.6.1 
Prior Therapy 
Prior therapy restrictions are described in the inclusion/exclusion criteria specified in 
Section 3. 
6.6.2 
Fluid and Food Intake  
There are no requirements for fasting and no restrictions for fluid and food intake by the 
patients during the study. 
6.6.3 
Patient Activity Restrictions 
There are no restrictions on patient activities and no requirement for patient confinement 
during the study. 
6.7 
Treatment Compliance 
MGA271 will be administered by healthcare professionals under the supervision of the Investigators. 
Records of MGA271 dose calculation, administration, and dosing regimen will be accurately 
maintained by site staff. The monitor will review dose calculation, administration and regimen as 
well as medication accountability during investigational site visits and at the completion of the study. 
6.8 
Packaging and Labeling 
MGA271 will be supplied in bulk, open-label, single-use vials. All investigational product will be 
labelled with a minimum of the protocol number, directions for use, storage conditions, expiry date 
(if applicable), batch number, the statements “For clinical trial use only,” and/or “CAUTION: New 
Drug – Limited by Federal (United States) Law to Investigational Use,” and the Sponsor's name and 
address. Please see the Pharmacy Manual for detailed information about the packaging of the study 
drug.  
6.9 
Storage and Accountability 
The vials containing study drug should be stored at 2°– 8° C (36°– 46° F) and must not be frozen or 
shaken. Protect from sunlight. To ensure compliance with storage conditions, temperature logs will 
be maintained. 
Because there is no preservative and drug loss occurs over time, administration of study drug should 
begin immediately after preparation but no later than 6 hours after preparation (see Pharmacy 
Manual). If there is a delay in administration of study drug such that it will not be administered on 
the day of preparation, the Clinical Project Manager should be notified immediately. Instructions on 
how to proceed will be provided. 

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The Investigator or his/her designee is required to maintain accurate drug accountability records. A 
binder containing instructions and the required accountability documentation will be provided to the 
Investigator or his designee. When the study is completed, copies of study drug accountability 
records must be sent to the Sponsor. The original drug accountability records must be maintained 
with the rest of the documentation in accordance with Section 9.3 of the protocol. 
Additional details regarding storage, handling, and accountability can be found in the Pharmacy 
Manual. 
6.10 
Investigational Product Disposition at End of Study 
Upon completion or termination of the study, all unopened vials of study medication must be 
returned to MacroGenics or its representative, unless the site has received written authorization 
from MacroGenics to destroy study drug at the site. All drug returns to MacroGenics or its 
representative must be accompanied by the appropriate documentation and be clearly identified by 
protocol number and study site number on the outermost shipping container. If MacroGenics 
approves the destruction of drug at the site, the Investigator must ensure arrangements are made for 
proper disposal and that appropriate records of disposal are documented and maintained and copies 
provided to the Sponsor. 
7. 
ADVERSE EVENTS AND REPORTING REQUIREMENTS 
An adverse event (AE) is defined as any untoward medical occurrence (symptom, sign, illness or 
experience) that develops or worsens in a research patient during a clinical study or within 30 days 
post-treatment, regardless of causality. This includes adverse clinical or laboratory findings, any 
adverse drug reaction (ADR), an illness with onset during the study, or an exacerbation of a 
preexisting illness or condition. Cancer progression should not be considered an AE, unless the 
investigator believes that the study treatment exacerbated the patient’s condition. Exceptions are if 
disease progression results in death or hospitalization while a patient is on study, in which case the 
disease progression is considered a serious AE. Abnormal findings on physical examination or 
diagnostic procedures are also considered AEs if: they are associated with clinical signs or 
symptoms; they require therapeutic intervention or additional diagnostic testing; they lead to dose 
modifications/termination of the study drug; or they are considered clinically significant by the 
investigator. All observed or reported AEs, regardless of their suspected causal relationship to the 
study drug, should be recorded on the Case Report Form (CRF). 
 The NCI CTCAE version 4.0 will be used for adverse event descriptions and grading 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf). These 
criteria are summarized in Appendix B. The type and severity of an AE, as well as its potential link to 
the study drug(s), will determine whether the event requires expedited reporting in addition to 
routine reporting. For all AEs, the investigator must pursue and obtain information to adequately 
determine the causality and outcome of the event, and to assess whether it meets criteria for a 
serious AE. In addition, follow-up of AEs should continue until the event and any sequelae resolve or 
stabilize at a level acceptable to the investigator and/or the medical monitor. 
7.1 
Recording and Grading 
7.1.1 
Recording 
All observed or volunteered adverse events, regardless of treatment group, severity, 
suspected causality, expectedness, or seriousness will be documented on the CRF. 
A clinically significant change in a physical examination finding or an abnormal test result 
(i.e., laboratory value) should be recorded as an AE, if it: 

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• 
is associated with accompanying symptoms 
• 
requires additional diagnostic testing or medical or surgical intervention 
• 
leads to a change in study dosing or discontinuation from the study 
• 
requires additional concomitant drug treatment or other therapy, or 
• 
is considered clinically significant by the investigator 
An abnormal test result that is subsequently determined to be an error does not require 
recording as an AE even if it originally met one or more of the above criteria. 
7.1.2 
Grading severity 
All adverse events will be graded for intensity on a scale of 0 to 5, according to the NCI 
CTCAE version 4.0 (see Table 2 and Appendix B). These criteria can be found at 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf 
Table 2 Intensity of Adverse Event 
Grade 
Description 
0 (none) 
No adverse event or within normal limits. 
1 (mild) 
Transient or mild discomfort; generally non-progressive; no limitation 
in daily activities; no medical intervention required. 
2 (moderate) 
Mild/moderate limitation in daily activities; some assistance may be 
required; no/minimal medical intervention required. 
3 (severe) 
Marked limitation in daily activities; some assistance usually required; 
medical intervention is required. 
4 (life-
threatening) 
Extreme limitation in daily activities; major assistance required; 
significant medical intervention required. 
5 (death) 
Fatal adverse event. 
 
7.1.3 
Attributing causality 
After grading for severity, the investigator must evaluate all clinical AEs and abnormal 
laboratory values for possible causal relationship to the study drug(s). Causality attribution 
will be decided using the criteria outlined in Table 3. 
Table 3 Relationship of Adverse Event to Study Drug 
Relationship 
Description 
Unrelated 
AE is clearly not related to the study drug (An event that does not meet 
any of the criteria below). 
Unlikely 
AE is doubtfully related to the study drug (An event that follows a 
reasonable temporal sequence after drug administration; that follows a 
known or expected response pattern; but that could more reasonably be 
explained by other characteristics of the patient’s clinical state). 
Possible 
AE may be related to the study drug (An event that follows a reasonable 
temporal sequence after drug administration; that follows a known or 

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expected response pattern; but that could just as readily be attributed to 
a number of other factors). 
Probable 
AE is likely related to the study drug (An event that follows a reasonable 
temporal sequence after drug administration; that follows a known or 
expected response pattern; that is confirmed by stopping/reducing the 
drug dose; and that could not be reasonably explained by the 
characteristics of the patient’s clinical state). 
Definite 
AE is clearly related to the study drug (An event that follows a 
reasonable temporal sequence after drug administration; that follows a 
known or expected response pattern; and that is confirmed by 
improvement on stopping/reducing the drug dose and reappearance on 
repeated exposure). 
 
Abnormal laboratory values of clinical significance that were present at baseline and did not 
change in severity or frequency during experimental therapy and those that can obviously 
be attributed to underlying disease will be recorded as unrelated and will not be considered 
when evaluating study drug toxicity. 
7.2 
Unexpected Adverse Events 
An unexpected adverse event is any event not associated by nature or intensity with the 
investigational agent(s) under study. A comprehensive list of adverse events and potential risks 
related to MGA271 is provided in this Protocol and in the Consent form. The study agent may cause 
allergic reactions in very rare instances. A severe allergic reaction could be life-threatening. 
Examples of allergic reactions include: rash; shortness of breath; wheezing; sudden drop in blood 
pressure; swelling around the mouth, throat, or eyes; fast pulse; and sweating. 
7.3 
Serious Adverse Events and Serious Adverse Drug Reactions 
The investigator must assess each event to determine if it meets the criteria for classification as a 
serious adverse event (SAE) or serious adverse drug reaction (ADR). An SAE/ADR is defined in the 
Code of Federal Regulations (21CFR312.32) as any event that: 
• 
results in death 
• 
is life-threatening 
• 
results in inpatient hospitalization or prolongation of existing hospitalization 
• 
results in persistent or significant disability or incapacity 
• 
results in congenital anomaly or birth defect 
• 
is medically significant in the opinion of the investigator 
All SAEs that occur any time while a patient is on study (i.e., as soon as the informed consent has been 
signed) or within 30 days of the last dose of study drug administration must be documented, 
regardless of the suspected relationship to the investigational agent(s). Any SAE occurring more than 
30 days after the last dose of the study drug(s) must be recorded if a causal relationship to the 
investigational agent(s) is suspected. 
7.3.1 
Progression of malignancy 
Progression of a patient’s malignancy should not be considered an AE unless, in the 
investigator’s opinion, study treatment resulted in an exacerbation of the patient’s condition. 

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If disease progression results in death or hospitalization while on study or within 30 days of 
the last dose of study drug administration, progressive disease will be considered an SAE. 
7.3.2 
Life-threatening events 
A life-threatening event is any AE that places the patient at immediate risk of death from the 
reaction as it occurs. It is not a reaction that, had it occurred in a more severe form, might 
have caused death. 
7.3.3 
Hospitalization or prolongation of hospitalization 
Hospitalization encompasses any inpatient admission (even if < 24 hours) resulting from a 
precipitating treatment-emergent adverse event. For chronic or long-term patients, 
inpatient admission also includes transfer within the hospital to an acute or intensive care 
inpatient unit. Hospitalizations for administrative reasons or a non-worsening preexisting 
condition should not be considered AEs (e.g., admission for workup of a persistent 
pretreatment laboratory abnormality, yearly physical exam, protocol-specified admission, or 
prostatectomy surgery). Hospitalization because of an unplanned event will be deemed an 
SAE. Preplanned treatments or surgical procedures should be noted in the baseline 
documentation. In the case of this study, all patients will have a preplanned prostatectomy 
surgery. 
Prolongation of hospitalization is any extension of an inpatient hospitalization beyond the 
stay anticipated or required for the original reason for admission. 
7.3.4 
Significant disability 
This is defines as a substantial disruption of the patient’s ability to conduct normal life 
functions and activities of daily living. 
7.3.5 
Congenital anomaly 
If the female partner of a male patient becomes pregnant during the course of the study, the 
treating physician must be notified immediately. All confirmed pregnancies must be 
immediately reported to the principal investigator and the medical monitor, and recorded in 
the CRF. All pregnancies will be followed until resolution (i.e., voluntary or spontaneous 
termination or birth) and assessed for congenital anomalies and birth defects. 
7.3.6 
Medical significance 
An event that is not fatal or life-threatening and that does not necessitate hospitalization 
may be considered serious if, in the opinion of the investigator, it jeopardizes the patient’s 
status and might lead to medical or surgical intervention to prevent any of the above 
outcomes. Such medically significant events could include allergic bronchospasm requiring 
intensive treatment in the emergency room or at home, blood dyscrasias that do not result in 
inpatient hospitalization, or the development of drug dependency or abuse. 
7.4 
Perioperative Adverse Events 
Complications of surgery or those occurring in the early post-operative period will be recorded. 
These include wound complications, estimated blood loss, post-operative infections, delayed wound 
healing, abnormal laboratory values, etc. Duration of hospital stay will be recorded. Additional 
medical examinations will be allowed at the request of patients during drug administration or at the 
discretion of the principal investigator for the evaluation of new adverse events that warrant 
physical examination. During and following completion of the study, patients should notify the study 

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staff of any problems that occur between visits or following study termination by telephone and, if 
necessary, will be evaluated by the investigator or study personnel at an unscheduled interim visit. 
Operative/perioperative events will be recorded as described in Section 7.1, and their severities will 
be categorized using the NCI CTCAE version 4.0 criteria. The relationship of these events to the 
investigational drug(s) will be determined by the principal investigator together with urologist co-
investigators and, if necessary, with the primary urologic surgeon. Reporting of these events will 
follow the same guidelines described in Section 7.5. 
7.5 
Reporting Adverse Events 
7.5.1 
Reporting serious adverse events (SAEs) 
IND application sponsors are required to notify FDA in a written safety report of: 
o 
any adverse experience associated with the use of the drug that is both serious and 
unexpected or 
o 
any findings from tests in laboratory animals that suggest a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, and 
carcinogenicity.  
  
Adverse event means any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality than 
an adverse reaction. 
 
Adverse reaction means any adverse event caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions where there is reason to conclude that the drug caused the event.   
 
Unexpected adverse event or suspected adverse reaction refers to an event or reaction that is not 
listed in the investigator’s brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator’s brochure is not required or available, is not consistent with the risk 
information described in the general investigational plan or elsewhere in the current IND application. 
 
Serious adverse event or suspected adverse reaction refers to an event or reaction that, in the view 
of either the investigator or sponsor, results in any of the following outcomes: 
• 
death, 
• 
a life-threatening adverse event,   
• 
in-patient hospitalization or prolongation of existing hospitalization, 
• 
a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or   
• 
a congenital anomaly or birth defect.    
 
Life-threatening adverse event or suspected adverse reaction is considered “life-threatening” if, in 
the view of the investigator or sponsor, its occurrence places the patient or subject at immediate risk 
of death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize 

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the patient or research subject and may require medical or surgical intervention to prevent one of 
the outcomes listed as serious.  
 
Mandatory Safety Reporting  
• 
Initial reporting: IND application sponsor must report any suspected adverse reaction or 
adverse reaction to study treatment that is both serious and unexpected.  
Unexpected serious suspected adverse reactions suggesting significant risk to human subjects must be 
reported to FDA as soon as possible but no later than within 15 calendar days following the sponsor’s 
initial receipt of the information. 
Unexpected fatal or life-threatening suspected adverse reactions represent especially important safety 
information and must be reported to FDA as soon as possible but no later than 7 calendar days 
following the sponsor’s initial receipt of the information. 
• 
Follow-up reporting: Any relevant additional information obtained by the sponsor that 
pertains to a previously submitted IND safety report must be submitted as a Follow-up IND 
Safety Report. Such report should be submitted without delay, as soon as the information is 
available but no later than 15 calendar days after the sponsor receives the information. 
 
All IND safety reports must be submitted on Form 3500A and be accompanied by Form 1571. The type 
of report (initial or follow-up) should be checked in the respective boxes on Forms 3500A and 1571.  
 
The submission must be identified as: 
• 
“IND safety report” for 15-day reports, or 
• 
“7-day IND safety report” for unexpected fatal or life-threatening suspected adverse reaction 
reports, or 
• 
“Follow-up IND safety report” for follow-up information. 
 
The report must be submitted to an appropriate Review division that has the responsibility to review the 
IND application under which the safety report is submitted. Each submission to this IND must be 
provided in triplicate (original plus two copies). Send all submissions to the following address: 
 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Division of Oncology Products 1 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
 
If the IND is not in eCTD (Electronic Common Technical Document format), other means of rapid 
communication (e.g., telephone, facsimile transmission, email) may be used. If the IND is not in eCTD 
format and the sponsor intends to submit 7-day IND safety reports by facsimile transmission or 
email, the sponsor should address the submissions to the Regulatory Project Manager and the Chief, 
Project Management Staff in the FDA review division that has responsibility for review of the IND. 
 
7.5.2 
Reporting requirements for the Sidney Kimmel Comprehensive Cancer Center (SKCCC) 
The principal investigator will notify the appropriate regulatory agencies of any SAEs 
occurring during the study period, regardless of causality. These agencies include the Sidney 
Kimmel Comprehensive Cancer Center (SKCCC) Data and Safety Monitoring Committee 
(DSMC), and the Institutional Review Board (IRB) and the Institutional Biosafety Committee 
(IBC) of the Johns Hopkins Medical Institutions (JHMI). Expedited reporting to the IND 
Sponsor by the PI within 24 hours is required for all SAEs (see Section 7.4.1). For SAEs that 

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are fatal, life-threatening, or treatment-related but non-life threatening: IRB/IBC reporting 
by the PI is required within 3 days. For unrelated SAEs, IRB/IBC reporting by the PI is 
required within 15 days. All other AEs should be documented on CRFs and submitted 
according to the standard data management guidelines. 
Adverse event information will be collected continuously throughout the duration of the 
study. Participants will be instructed to notify their treating provider of any new signs or 
symptoms, and providers will actively assess patients for adverse events at each visit 
(including by evaluation of laboratory studies). The investigator will assess each AE for its 
severity and for its relationship to the study drug, and all events Grade 1 or higher will be 
documented on CRFs and then reported as described above within the required time frame. 
Any AE occurring while a patient is on study (i.e. after informed consent has been signed) or 
within 30 days of study termination requires reporting. AEs occurring later than this must 
still be reported if a causal relationship with the study drug is suspected. 
For all AEs, the investigator must pursue and obtain information to adequately determine 
the causality and outcome of the event, and to assess whether it meets criteria for a SAE. In 
addition, follow-up of an AE is required until the event either resolves or stabilizes. Initial 
reporting of an AE should include at a minimum the patient number, age, the dose at which 
the event occurred, and the type and severity of the event. Follow-up information including 
causality, duration, outcome, action taken, and concomitant medications should be reported 
soon thereafter. 
The principal investigator must keep copies of all CRFs and other AE information, including 
correspondence with the IRB and/or FDA, for as long as required to comply with national 
and international regulations (generally at least 3 years after study completion). 
7.6 
Pregnancy 
Pregnancy is not an AE unless it results in congenital anomaly or birth defect, in which case it is a 
SAE. If the partner of a male patient should become pregnant while he is participating in the study, 
the patient should inform his treating physician immediately. All pregnancies must be reported at 
once to the principal investigator and medical monitor. All confirmed pregnancies will be followed 
until birth or until voluntary or spontaneous termination.
8. 
OUTCOME ASSESSMENT 
8.1 
Radical Prostatectomy Specimen 
Most of the study outcomes in this immunologic trial will depend on collection of prostate tissue 
from prostatectomy specimens. All pathologic specimens will be handled in routine fashion by the 
operating room (OR) staff, except that as soon as the specimen is removed the OR nurse will directly 
page a tissue harvesting technician that is part of the Brady Urological Research Institute Prostate 
Specimen Repository Team. Accessioning of pathology specimens will be coordinated in the OR areas 
by the Departments of Urology and Pathology. A study technician will be available to the pathologist 
receiving the specimen to assure that the tissue is handled appropriately for the intended bioassays. 
At the time of harvesting, the pathologist will apply ink and cut the prostate specimen in transverse 
sections. The specimen will be fixed in 10% phosphate buffered formalin, and tissue blocks will be 
paraffin-embedded and sectioned at 4 μm thickness for routine histologic evaluation and for 
immunohistochemical determinations. Fixation should occur as soon as possible after operative 
removal of the prostate, and ideally within 30-60 minutes. Assessment of index tumors for Gleason 
grade, nodal involvement, and pathologic staging will be conducted in usual fashion and will be 
provided to the patient for prognostic information. After the pathology report is available, a database 

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will be established and all information from the pathology reports of all samples will be included. 
Tumor blocks and/or additional unstained slides will be collected for study-specific quantitative 
immunohistochemical evaluations. 
8.2 
Primary Endpoint 
8.2.1 
Rate of adverse events 
All subjects receiving at least one dose of the study drug will be evaluated for safety by 
monitoring symptoms, physical examinations, and laboratory tests. Adverse events will be 
classified and graded according to the NCI Common Toxicity Criteria version 4.0 (see 
Appendix B). The absolute number and frequency of each adverse event will be reported, 
and subdivided according to toxicity grade. A description of adverse events by treatment 
arm will also be reported. A particular adverse event occurring more than once in the same 
subject will be counted only once and at its worse grade. 
8.2.2 
In expansion cohort (amendment 1): 
• 
All subjects receiving at least one dose of the study drug will be assessed for  PSA0 Response 
Rate (Undetectable PSA level <0.1 ng/mL) at 12 months following radical prostatectomy  
 
8.3 
Secondary and Exploratory Endpoints 
8.3.1 
Markers of apoptosis 
The primary measure of treatment effect in this study will be achieved by quantification of 
tumor cell apoptosis in prostate tumor specimens of treated patients.  Tissue microarrays 
(TMAs) from formalin-fixed tumor samples will be analyzed for the degree of tumor 
apoptosis using immunohistochemical staining for activated caspase 3 (Marcelli et al 2000), 
or by using the method of terminal deoxynucleotidyl transferase (TdT)-mediated 
deoxyuridine triphosphate (dUTP) nick end labeling (i.e. TUNEL assay) (Furuya et al 1995). 
The in situ Cell Death Detection Kit (Roche, Indianapolis, IN) may be used to perform TUNEL 
reactions. Quantification of staining percentage will be achieved using the Aperio 
ScanScope® CS instrument (Aperio Technologies, Vista, CA) as described in Section 8.3.3. 
This endpoint will be expressed as the mean staining percentage in tumor tissue. Analyses 
will be performed in the laboratory of Dr Angelo DeMarzo. The contact information for the 
DeMarzo laboratory is listed below: 
Angelo DeMarzo, MD, PhD 
CRB1 - Room 151 
1650 Orleans Street 
Baltimore, MD 21231 
Phone:  (410) 614-5686 
Fax: (410) 502-9817 
Email: ademarz@jhmi.edu 
8.3.2 
Markers of cell proliferation 
TMAs from fixed tumor samples will be analyzed for the degree of tumor cell proliferation 
using the validated marker, Ki-67. This will be achieved by immunohistochemical staining 
(Berges et al 1995; Rubin et al 2002), using the Ki-67 monoclonal antibody (Dako North 
America, Carpineteria, CA). Quantification of staining percentage will be performed using the 
Aperio ScanScope® CS instrument (Aperio Technologies, Vista, CA) as described in Section 

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8.3.3. This endpoint will be expressed as the mean staining percentage in tumor tissue. 
Assays will be performed in the laboratory of Dr DeMarzo. 
8.3.3 
CD8+ T cell infiltration 
To assess the immune response to MGA271, we will quantify the extent of CD8+ T cell 
infiltration into the prostate from harvested prostate glands. This will be done using 
immunohistochemical staining methods. This endpoint will be expressed as the mean CD8+ T 
cell staining percentage in harvested tumor tissue. We will also attempt to quantify prostatic 
CD4+ T cell infiltration and Treg infiltration, as well as to determine the CD8/Treg ratio and the 
CD4/Treg ratio.  
Analysis of this endpoint will be achieved by preparing tissue microarrays (TMAs) using the 
highest-grade/largest tumor per patient and sampling it with 100-fold redundancy. All 
tissues will first be fixed in 10% neutral buffered formalin and processed into paraffin 
blocks. For each immunohistochemical stain (e.g. CD8+ T cell stain, CD4+ T cell stain, Treg 
stain), TMA slides will be scanned using the Aperio ScanScope® CS instrument (Aperio 
Technologies, Vista, CA) and TMA cores will first be assigned a diagnosis by the study 
pathologist and will then be  subjected to semi-automated image analysis using the Aperio 
system. For each biomarker, we will divide the area of brown DAB staining by the area of 
epithelial cells on the TMA core, obtaining a staining percentage. The area of epithelium will 
be obtained on each TMA core by staining with cytokeratin-8 and using automated image 
analysis. Cores with both tumor and normal tissue will be excluded if they contained >10% 
of the other component. 
For CD8 staining, slides will be steamed for 20 minutes in citrate antigen retrieval solution 
(Vector Laboratories, Burlingame, CA) followed by  incubation with a mouse monoclonal 
anti-CD8 antibody for 45 minutes at room temperature (Dako, Carpinteria, CA). For CD4 
staining, slides will be steamed for 40 minutes in high pH antigen retrieval solution (Dako, 
Carpinteria, CA) and then incubated with a mouse monoclonal anti-CD4 antibody for 45 
minutes at room temperature (Serotec, Kidlington, UK). For Treg analysis, cells will be stained 
for the FoxP3 protein by steaming slides for 40 minutes in high pH antigen retrieval solution 
(Dako, Carpinteria, CA) and incubating them with a mouse monoclonal anti-FoxP3 antibody 
for 45 minutes at room temperature (eBioscience, San Diego, CA, 1:1000 dilution). In all 
cases, poly-HRP-conjugated anti-mouse IgG Ab (Dako, Carpinteria, CA) will be used as the 
secondary antibody. Staining will be visualized with diaminobenzidine (Sigma, Saint Louis, 
MO) and slides will be counterstained with hematoxylin. 
Images of each TMA core will be captured by automated scanning of TMA slides using the 
Aperio ScanScope® CS instrument (Aperio Technologies, Vista, CA). Captured images will be 
imported into the TMAJ Images Application program (http://tmaj.pathology.jhmi.edu). 
Histological diagnoses (normal, atrophy, prostatic intraepithelial neoplasia, cancer) will be 
applied to all images used for the analyses by a pathologist. In addition, for TMA spots 
containing more than one type of lesion, the percentage of each diagnosis will be noted. All 
images and data will be available for viewing/downloading at 
http://demarzolab.pathology.jhmi.edu/Pubs.html. For image analysis, we will use a custom 
open source software package, FRIDA (Framework for Image Dataset Analysis; 
http://sourceforge.net/projects/fridajhu), for the evaluation of red-green-blue (RGB) color 
image datasets, including those generated from scanning of tissue microarray slides. To 
analyze CD4, CD8 and FoxP3 (Treg) staining, hue-saturation-brightness (HSB) segmentation 
ranges for brown DAB staining will be defined from the tissue microarray image set, and the 
total number of pixels in every image that fall within the defined parameters for brown DAB 
staining will be calculated, reflecting the total area of brown DAB staining for each spot. For 

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every spot, a “staining ratio” for each of the three proteins will be calculated by dividing the 
total area (in pixels) of brown DAB staining by the average TMA spot area. 
Previous TMA studies conducted by Angelo DeMarzo, MD PhD and Charles G. Drake, MD PhD 
have defined the extent of T cell infiltration into human prostate glands using prostatectomy 
specimens. In normal prostate tissue, the mean staining percentage for CD8+ T cells is 0.29% 
(interquartile range, IQR, 0.13% - 0.39%) while in tumor tissue, the mean percentage of 
CD8+ T cells is 0.42% (IQR 0.07% - 0.71%). The corresponding values for CD4+ T cell 
infiltration in normal and tumor tissue are 0.16% (IQR 0.04% - 0.18%) and 0.25% (IQR 
0.01% - 0.32%), respectively. The corresponding values for Treg infiltration in normal and 
tumor tissue are 0.03% (IQR 0.02% - 0.04%) and 0.06% (IQR 0.02% - 0.08%), respectively 
(Gurel and DeMarzo, unpublished data).  
The above analyses will be performed in the laboratory of Angelo DeMarzo, MD PhD. A 
detailed description of these methodologies has previously been published (Zha et al 2001; 
Faith et al 2004; Gurel et al 2008).  
8.3.4 
PD-L1 expression  
PD-L1 expression in prostate tumor specimens will be assessed by IHC in the primary core 
specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). 
This endpoint will be expressed as the mean staining percentage of PD-L1 in tumor tissue. 
8.3.5 
Regulatory T cell (Treg) infiltration 
The method for quantifying Treg density from harvested prostate tissue is as described in 
Section 8.3.3. This endpoint will be expressed as the mean staining percentage in tumor 
tissue. 
8.3.6 
CD4+ T cell infiltration 
The method for quantifying CD4+ T cell density from harvested prostate tissue is as 
described in Section 8.3.3. This endpoint will be expressed as the mean staining percentage 
in tumor tissue. 
8.3.7 
Mean NK cell density in tumor tissue from harvested prostate glands of patients.  
The method for quantifying NK cell density from harvested prostate tissue is as described in 
Section 8.3.3. This endpoint will be expressed as the mean staining percentage in tumor 
tissue. 
8.3.8  
FC Receptor Genotyping 
Determination of Fc receptor genotype (CD16A, CD32A, CD32B).  To be shipped to 
MacroGenics for analysis. 
8.3.9 
Sera for Immunoassays  
Sera for immunoassays will be collected at each time point (Pre-treatment, Radical Prostatectomy, and 
Follow-up), 
 
8.3.10 
PBLs  
Whole blood (100cc) will be collected for PBLs at each time point ((Treatment Day 1, 
Treatment Day 36, and Follow-up day 30), 
8.3.11 
TCR Repertoire 

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To assess changes in TCR repertoire in peripheral and tumor T-cells following treatment 
with MGA271, TCR Deep Sequencing analysis will be performed via Adaptive Biotechnology 
(Seattle, WA). For tumor T-cell analysis, a tumor sample (10 mg fresh frozen or 25 mg FFPE) 
will be used. For peripheral T-cell analysis, peripheral whole blood samples (2x10 mL) pre-
treatment, at time of surgery, and 30 and 90 days post-op will be used. Note: Adaptive 
Biotechnology requires a min of 3ug DNA (tissue or blood) for deep sequencing. 
8.3.12 
 B7-H3 expression  
B7-H3 expression in prostate tumor specimens will be assessed by IHC in the primary core 
specimens (pre-treatment) and in the prostatectomy surgical specimens (post-treatment). 
This endpoint will be expressed as the mean staining percentage of B7-H3 in tumor tissue. 
8.3.13 
Enoblituzumab (MGA271) drug distribution 
To analyze MGA271 drug levels in prostate tumor specimens of treated patients, fresh frozen 
sections will be evaluated by IHC for evidence of MGA271 drug distribution. Fresh frozen 
section samples will be shipped to MacroGenics for analysis. This endpoint will be expressed 
as positive or negative detection of MGA271 in tumor tissue.  
8.3.14 
Tissue androgen concentrations 
Tissue concentrations of testosterone and 5α-dihydrotestosterone (DHT) will be measured 
using a highly sensitive liquid chromatography–electrospray ionization tandem mass 
spectrometry method using a high proton affinitive derivatization of the 17β-hydroxyl group 
of testosterone and DHT with picolinic acid, and a mobile phase consisting of MeCN–MeOH–
H2O–formic acid and a conventional octadecylsilica (ODS) column (Yamashita et al 2009). 
Purification of the derivatives will be carried out using solid-phase extraction with the ODS 
cartridge. By this method, testosterone and DHT will be determined simultaneously with 
limits of quantification of 0.5 pg and 1 pg/3 mg of prostate tissue, respectively. 
8.3.15 
Androgen receptor (AR) quantification 
The method for quantifying androgen receptor (AR) density from harvested prostate tissue 
is similar to that described in Section 8.3.3, and will rely on immunohistochemical staining 
for the AR protein. This endpoint will be expressed as the mean staining percentage in tumor 
tissue. 
8.3.16 
Pathological complete responses (pCR) 
This will be defined as the absence of tumor identification by the study pathologist on 
standard histological analysis of the resected prostate specimens. The endpoint will be 
expressed as the proportion of men achieving a pCR. 
8.3.17 
PSA response rates 
This will be defined as the proportion of patients who achieve an undetectable PSA (<0.1 
ng/mL) by 3 months after prostatectomy. The endpoint will be expressed as the proportion 
of men achieving a PSA response. 
8.3.18 
Time to PSA recurrence  
This will be defined as the interval from the time of prostatectomy to the time when the 
serum PSA is ≥0.2 ng/mL. PSA will be measured approximately 1 month after prostatectomy, 
and every 3 (±1) months during the first post-operative year and every 6 (±2) months 
during the second and third post-operative years. For subjects who have not yet 
demonstrated PSA relapse at the time of censoring, patients will be censored at the date of 

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the last assessment that shows a lack of PSA recurrence. This outcome will be expressed as a 
median and will be determined using the Kaplan-Meier method. 
8.3.19 
In expansion cohort (Amendment 1): assessment of Gleason grade change (prostatectomy 
Gleason sum vs. core biopsy Gleason sum) post neoadjuvant Enoblituzumab treatment 
 
This will be defined by comparing highest Gleason grade from pre-treatment biopsy versus 
highest Gleason grade from post-treatment prostatectomy. This endpoint will be expressed 
as the proportion of men achieving a Gleason score change.  
8.3.20 
Global expression profiling of pre and post treatment tumor tissue using single cell RNA    
sequencing, the immune NanoString immunopanel and/or microarrays 
Expression profiling will be conducted as per established protocols for single cell RNA seq, 
Nanostring, and microarray 
8.3.21 
IHC analyses of CD137, CD16 and/or CD107A across potential immune infiltrate following 
Enoblituzumab 
 
CD137, CD107A, and CD16 expression in prostate tumor specimens will be assessed by IHC 
in the prostatectomy surgical specimens (post-treatment). This endpoint will be expressed 
as the mean staining percentage of each of these in in tumor tissue. 
 
9. 
REGULATORY AND REPORTING REQUIREMENTS 
Contact details for personnel connected with this study are provided on the title page at the front of 
this protocol. Patient registration procedures are described in Section 4. 
9.1 
Regulatory Responsibilities 
9.1.1 
Protocol chair 
The protocol chair (=PI) is responsible for the following tasks: 
• 
Coordinating, developing, writing, submitting, and obtaining IRB-approval for the 
protocol as well as its subsequent amendments. 
• 
Assuring that all study personnel are using the correct version of the protocol. 
• 
Taking responsibility for the overall conduct of the study and for monitoring the 
progress of the study. 
• 
Reviewing and ensuring reporting of serious adverse events (SAEs). 
• 
Reviewing data from all patients. 
9.1.2 
Study Coordinator 
The study coordinator is responsible for the following tasks: 
• 
Ensuring that IRB approval has been obtained prior to patient registration, and 
maintaining copies of IRB approvals (including approval of amendments). 
• 
Managing patient registration. 
• 
Collecting and compiling data from each patient. 

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• 
Establishing procedures for documentation, reporting, and submission of AEs/ SAEs to 
the protocol chair (Name) and other applicable parties. 
• 
Facilitating audits by securing selected source documents and research records from 
participating patients for audit. 
9.1.3 
Study personnel 
Study personnel (co-investigators, research nurses) are responsible for these tasks: 
• 
Following the protocol as written, and Good Clinical Practice (GCP) guidelines. 
• 
Submitting data to the project manager. 
• 
Registering all patients by submitting the patient registration form and signed informed 
consent form promptly. 
• 
Providing sufficient experienced clinical and administrative staff and adequate facilities 
and equipment to conduct the trial according to the protocol. 
• 
Maintaining regulatory binders and providing copies of all required documents to the 
project manager. 
• 
Collecting/submitting data according to the schedule specified by the protocol. 
9.2 
Data Management 
Data collected during this study will be entered into a secure database. The study coordinator will be 
responsible for the initial study configuration and setup of the database and for any future changes. 
9.2.1 
Case report forms 
Case report forms (CRFs) will be generated by the study coordinator for the collection of all 
study-related data. Investigators and study personnel will be responsible for ensuring that 
the CRFs are kept up-to-date. 
9.2.2 
Source documents 
Investigators and study personnel will record clinical data in each patient’s source 
documents (i.e., the patient’s medical record). Source documentation will be made available 
to support the patient research record. Study monitors will review entries on the CRFs at 
regular intervals, comparing the content with the source documents. 
9.2.3 
Record retention 
The investigator will maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified. After study 
closure, the investigator should maintain all source documents, study-related documents, 
and the CRFs. Because the length of time required for retaining records depends upon a 
number of regulatory and legal factors, documents should be stored until the investigator is 
notified that the documents may be destroyed. In this study, records are to be retained and 
securely stored for a minimum of 3 years after the completion of all study-related activities. 
9.3 
Study Monitoring and Quality Assurance 
This is a DSMP Level II study under the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center 
(SKCCC) Data Safety Monitoring Plan (12/6/2012) Data Monitoring of this protocol will occur on a 
regular basis with the frequency dependent on the rate of subject accrual and the progress of the 
study. The protocol will be monitored internally at SKCCC by the Principal Investigator and 

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externally by the SKCCC CRO in accordance with SKCCC guidelines. Trial monitoring and reporting 
will be done through the Safety Monitoring Committee (SMC) at SKCCC. 
Additionally, scheduled meetings will take place monthly and will include the protocol principal 
investigator, research nurse, data manager, and, when appropriate, the collaborators, 
subinvestigators, and biostatistician involved with the conduct of the protocol. 
 
During these meetings the investigators will discuss matters related to: safety of protocol 
participants, validity and integrity of the data, enrollment rate relative to expectation, characteristics 
of participants, retention of participants, adherence to protocol (potential or real protocol 
violations), data completeness, and progress of data for secondary objectives. 
10. 
STATISTICAL CONSIDERATIONS 
10.1 
Study Design and Sample Size 
This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, 
and immunogenicity of neoadjuvant MGA271 given weekly for 6 doses beginning 50 days prior to 
radical prostatectomy in men with high-risk localized prostate cancer.  Our primary objective is to 
characterize safety, tolerability, and feasibility of treatment of men with Enoblituzumab in the 
neoadjvuant setting.  The trial will monitor toxicity and safety, as well as surgery related adverse 
events. (see Section 10.2.1).  The secondary objective will be to evaluate immune response consistent 
with the agent’s proposed mechanism of action (MOA), antibody-dependent cellular cytotoxicity 
(ADCC).  Tumor cell death will be quantified by Caspase 3 staining, and post-treatment apoptotic 
index compared with that from the pre-treatment biopsy.  The sample size is driven by detecting a 
pharmacodynamic effect of the agent based on the key secondary endpoint of tumor cell death. A 
biologically meaningful treatment effect will be deemed to be one where the tumor cell apoptosis is 
two-fold higher after MGA271 therapy. Previous study showed that baseline apoptosis, measured by 
Caspase staining, is 0.06 +/- 0.08 (Mean +/-SD) for Gleason 4 and 0.2 ± 0.2 for Gleason 3 (Kim et al. 
2016). Based on this data, we assume that the coefficient of variation of tumor cell death measure is 
1.2 and the correlations between the measures pre- and post-treatment is moderate at 0.4, 16 
subjects will provide 88% power to detect a 2-fold increase in apoptotic tumor cells after the 
treatment compared to baseline, using a one-sided paired t-test with significance level 0.05.   
In Amendment 1, the study was expended to enroll an additional 16 patients for a total of 32 patients 
to continue evaluating safety and better estimate the clinical benefit of Enoblituzumab in terms of 
undetectable PSA level (<0.1 ng/mL) at 12 months following radical prostatectomy. 
Patients will be replaced if they are removed from the study after signing the informed consent but 
before undergoing radical prostatectomy. Patients receiving at least one dose of the study drug will 
be included in both safety and efficacy analyses. 
10.2 
Study Endpoints 
10.2.1 
Analysis of the primary endpoints 
Safety and feasibility 
Frequency of adverse events will be described using summary statistics. The proportion of 
patients with an adverse event will be reported with an exact binomial 95% confidence 
interval. All subjects receiving at least one dose of the study drug(s) will be evaluable for 
toxicity. 

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Early stopping rules for toxicity:  Toxicity will be monitored closely and continuously.  Any 
grade-3/4 local reactions (erythema, swelling, pain) attributable to MGA271 or Grade 3 
infusion-related reaction or cytokine release syndrome that lasts ≥ 12 hours will be considered 
AEs for purposes of this stopping rule. A grade 4 infusion related reaction of any duration 
will be considered AEs for purposes of this stopping rule. If the risk of these adverse events 
appears to be higher than 33%, we will temporarily halt the study pending dose 
modification. Specifically, we apply a Bayesian toxicity monitoring rule that suspends the 
enrollment if the posterior probability of risk being larger than 0.33 is 65% or higher. The 
monitoring rule uses beta (1.5, 5.5) as prior distribution. This means that our prior guess at 
the proportion of toxicity is 21%, and there is 90% probability that this proportion is 
between 3% and 49%. The decision rule for toxicity stopping is as follows:  
 
Study termination 
if:  
3 AEs 
4 AEs 
5  
6  
7  
8  
9 
10 
11 
12 
13 
In number of 
patients between: 
3 - 4 
5 - 7 
8 - 
10 
11 - 
12 
13 - 
15 
16 - 
18 
19 - 
21 
22 - 
24 
25 - 
27 
28 - 
30 
31-
32 
 
For example, we will interrupt the accrual if 3 patients have AEs among the first 4 receiving 
treatment. If 4 or more out of the first 5-7 patients have AEs, we will suspend accrual.  
The operating characteristics of the stopping rule are shown below and are based on 5000 
simulations: 
Risk of AE 
0.20 
0.25 
0.30 
0.33 
0.40 
0.45 
% of Time study stops 
7.5% 
18% 
33.7% 
46% 
54.6% 
73.3% 
Expected sample size 
30.3 
28.2 
25.3 
22.8 
21.2 
17.3 
 
 
Early stopping rule for feasibility:  We do not anticipate an increase in the surgical 
difficulty with the use of neoadjuvant MGA271. Men who have had acute (post-biopsy) and 
prolonged issues (chronic prostatitis) with prostate infection/inflammation are fairly 
routine in urologic surgical practice, and we anticipate that the immune infiltrate potentially 
induced by MGA271 would not pose a substantial increase in surgical difficulties. However, 
in addition to safety, feasibility will be monitored separately. The feasibility rule for this 
study will be based on a change in surgical outcomes beyond what may be expected for 
patients without presurgical interventions and that may be attributable to the study drug. 
These events would include: (1) average blood loss in excess of 2500 mL, (2) average 
operative time in excess of 3.5 hours, and (3) average hospital stay in excess of 4 days, (4) 
systemic symptoms (fevers, rash, myelosuppression) compromising the planned surgery. 
These values are approximately 2 standard deviations above the average surgical outcomes 
for men undergoing radical prostatectomy at Johns Hopkins Hospital. 
We expect no surgery complication in at least 90% cases. We will monitor this endpoint after 
every patient. If it becomes apparent that the surgeries are being negatively impacted by the 
pre-surgical investigational treatments, then the study will be suspended for review. Again, 
we apply a Bayesian monitoring rule that suspends the enrollment if the posterior 
probability of complications > 0.10 is 80% or higher. The monitoring rule uses beta (1, 9) as 
prior distribution, based on the expectation that these treatments will not impact the 

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feasibility of surgery. Instances where the study would be temporarily suspended are listed 
below.    
Stopping rules: 
Not feasible if the 
observed number of 
surgical 
complications is:  
2  
3 
4  
5  
6 
In number of 
patients between: 
2 - 6 
7 - 14 
15 - 22 
23 - 30 
31 - 32 
 
The operating characteristics of the stopping rule are shown below and are based on 5000 
simulations: 
Risk of surgical 
complication 
0.025 
0.05 
0.10 
0.15 
0.20 
% of Time study stops 
1.1% 
5.9% 
29.2% 
57.7% 
81.4% 
Expected sample size 
31.7 
30.7 
26.4 
20.9 
15.3 
 
10.2.1.1 For expansion Amendment 1 
Estimation of PSA0 Response Rate (Undetectable PSA level <0.1 ng/mL) at 12 months following 
radical prostatectomy 
Our primary efficacy endpoint will be to estimate the clinical benefit of neoadjuvant 
Enoblituzumab in terms of undetectable PSA level (<0.1 ng/mL) at 12 months following 
radical prostatectomy. The estimate and corresponding 90% confidence interval based on 
32 patients is listed in the table below.  
 
Observed N with 
undetectable PSA 
Observed rate 
90% CI 
0 
0 
0% - 7.8% 
1 
3.1% 
0.7% - 12.9% 
2 
6.2% 
2.1% - 17.2% 
3 
9.4% 
3.8% - 21.3% 
 
10.2.2 
Analysis of the secondary  and exploratory endpoints 
The secondary endpoints of this study have previously been defined (see Section 8.3). The 
statistical analysis of these endpoints is described below. Data transformation will be 
performed when they are not normally distributed. 
• 
Apoptotic markers. The primary objective of pharmacodynamics effect of this study is to 
determine the immunologic response consistent with the agent’s proposed mechanism of 
action (MOA), antibody-dependent cellular cytotoxicity (ADCC). Tumor cell death will be 
quantified by TUNEL staining, Caspase 3 staining, and FcGamma staining and will be 
expressed as the mean staining percentage in tumor samples. Standard deviations, 95% 
confidence intervals, and ranges will also be reported where appropriate. Means will be 

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compared pre-treatment (from pre-treatment biopsies) vs. post-treatment using paired 
sample test.  
• 
Proliferation markers. Ki-67 staining will be expressed as the mean staining percentage in 
tumor samples. Standard deviations, 95% confidence intervals, and ranges will also be 
reported where appropriate. Means will be compared pre-treatment vs. post-treatment 
using paired sample test. 
• 
CD8+ T cell infiltration. Mean CD8+ T cell staining percentage in harvested prostate tissues 
will be reported. The standard deviation, 95% confidence interval, median, and range of 
values will also be reported where appropriate. Since the CD8+ T cell quantity is a ratio 
variable and the distribution is skewed, the log transformation will be used for the analysis. 
Tissue microarrays (TMAs) using the highest-grade/largest tumor per patient and sampling 
it with 100-fold redundancy will be used for CD8+ T cell quantification.  We expect that 3-
50% of the spots per patient will be assigned a carcinoma diagnosis by the study pathologist.  
Cores with both tumor and normal tissue will be excluded if they contain >10% of the other 
component.  The percent positive staining score for CD8+ T cells in the spots classified as 
tumor will be used to quantify the outcome.  The mean will be used to pool multiple spot 
measurements for each patient. 
• 
PD-L1+ cell density. The methods for quantifying and analyzing PD-L1 cell density will be 
similar to those described for CD8+ T cell infiltration. Descriptive statistics and graphical 
summaries will be provided. 
• 
Regulatory T cell (Treg) density. The methods for analyzing Treg infiltration will be similar 
to those described for CD8+ T cell infiltration. Descriptive statistics and graphical summaries 
will be provided. In addition, the CD8+/Treg ratio and the CD4+/Treg ratio will be computed, 
and reported using descriptive statistics. 
• 
CD4+ T cell density. The methods for quantifying and analyzing CD4+ T cell infiltration will 
be similar to those described for CD8+ T cell infiltration. Descriptive statistics and graphical 
summaries will be provided. 
• 
Mean NK cell density. The methods for quantifying and analyzing NK cell infiltration will be 
similar to those described for CD8+ T cell infiltration. Descriptive statistics and graphical 
summaries will be provided. 
• 
Tissue androgen concentrations. Intraprostatic androgen concentrations (i.e. testosterone 
and dihydrotestosterone) will be summarized descriptively. 
• 
Enoblituzumab (MGA271) drug distribution. Intraprostatic Enoblituzumab staining 
concentrations will be summarized descriptively.  
• 
Androgen receptor (AR) quantification. Androgen receptor (AR) staining concentrations 
will be summarized descriptively. 
• 
Pathological complete responses (pCR). This will be defined as an absence of tumor 
identification on standard histological analysis of the resected prostate specimens. 
• 
PSA response rates. This will be defined as an undetectable PSA (<0.1 ng/mL) at 3 months 
after prostatectomy. The proportion of patients achieving a PSA response will be reported. . 
• 
Time to PSA recurrence. This will be defined as the interval from prostatectomy to the time 
when the serum PSA is ≥0.2 ng/mL. For subjects who have not yet demonstrated PSA 
recurrence at the time of censoring, patients will be censored at the date of the last 

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IRB#: IRB0010377                                                                                                                                                     Johns Hopkins University  
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assessment that shows a lack of PSA recurrence. The median time to PSA recurrence after 
prostatectomy (i.e., the median PSA-recurrence-free survival) will be estimated with 95% 
confidence intervals using Kaplan-Meier survival analysis.  
• 
Gleason grade change post neoadjuvant Enoblituzumab treatment from pre-treatment 
biopsy. This will be calculated utilizing the highest Gleason grade from the pre-treatment 
biopsy and the post-treatment prostatectomy.   
 
10.3 
Analysis Populations 
10.3.1 
Intention-to-treat population 
All patients who meet eligibility criteria and receive at least one dose of the study drug will 
be included in the analysis of the primary and secondary endpoints, even if there are 
subsequent protocol deviations. However, in cases where prostatectomy is not performed or 
if adequate surgical tissue is not collected, then determination of the secondary endpoints 
(apoptosis/proliferation marker analysis, tissue CD8+ T cell analysis) will not be possible. 
Patients will be replaced if they are removed from the study after signing the informed 
consent but before receiving the study drug. 
10.3.2 
Safety population 
All patients enrolled in the study will be included in the safety analysis population and 
considered evaluable for toxicity from the time of their first dose of the study drug(s). 
Patients never receiving any of the study drugs will not be included in this analysis. 
Demographic and baseline characteristics for the safety population will be summarized by 
number and percent for categorical data and by descriptive statistics for continuous data. 
10.4 
Safety Analysis 
10.4.1 
Evaluation of adverse events 
Treatment-emergent adverse events will be translated from investigator terms to MedDRA 
version 6.0 terminology and summarized (number and percentage of patients) for all 
patients who receive at least one dose of the study drug(s). Adverse event summaries will be 
organized by body system, frequency of occurrence, intensity (i.e., severity grade), and 
causality or attribution. Patients who experience an adverse event more than once will be 
counted only once. The occurrence with the maximum severity will be used to calculate 
intensity. 
10.4.2 
Evaluation of serious adverse events and premature withdrawals 
Adverse events deemed serious and those resulting in early treatment withdrawal or death 
will be summarized separately. Narrative paragraphs will be generated to describe the 
circumstances surrounding each SAE and each death. 
10.4.3 
Evaluation of laboratory parameters and assays 
Abnormal laboratory parameters (e.g. electrolyte levels, liver function tests, renal function 
tests, complete blood counts) will be summarized, and clinically significant changes from 
baseline will be discussed. 

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11. 
PROTECTION OF HUMAN SUBJECTS 
11.1 
Ethical Considerations 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP) guidelines 
established by the International Conference on Harmonization (ICH), and the ethical standards set 
forth in the Declaration of Helsinki of 2004 (these documents may be found at 
www.wma.net/e/policy/b3.htm and www.laakariliitto.fi/e/ethics/helsinki.html). Review of this 
protocol by the Institutional Review Board (IRB)/Ethics Committee (EC), and the performance of all 
aspects of the study including acquisition of informed consent, must also be in accordance with the 
principles elaborated in the Declaration, as well as the ICH guidelines (Code of Federal Regulations 
(CFR), Title 21: Part 50 and Part 312). The principal investigator will be responsible for submitting 
documents to the IRB/EC, and obtaining written approval for the protocol prior to study initiation. 
The approval of both the protocol and the informed consent must specify the date of approval, 
protocol number and version, and amendment number. The principal investigator is also responsible 
for notifying the IRB/EC of any serious deviations from the protocol, or other circumstances that may 
result in added risk to participating patients. 
11.2 
Protocol Amendments 
Before starting the study, the protocol must be approved by the IRB/EC, the JHU Institutional 
Biosafety Committee (IBC), the FDA, and the Recombinant DNA Advisory Committee (RAC). 
Amendments to the protocol are subject to IRB approval before instituting. Any amendments made 
after IRB/EC approval is granted must be resubmitted to the IRB/EC for new approval. 
11.3 
Written Informed Consent 
Before obtaining consent, members of the study team must review the rationale for the treatment 
program with the patient. The discussion will review the alternatives available, the potential benefits 
of this program, the risks and the probability of their occurrence, and the procedures to minimize 
these risks. Should an adverse event occur, the provisions available to ensure medical intervention 
must also be reviewed. Why the risks are reasonable in relation to the anticipated benefits, 
incentives, or costs that will/may be incurred as a result of participating in the study, as well as the 
efforts to maintain confidentiality, should also be discussed with the patient. 
Patients will be required to sign and date (in triplicate) a statement of informed consent that meets 
the requirements of the Code of Federal Regulations (Federal Register Vol. 46, No. 17, January 27, 
1981, part 50) and the IRB. The consent form should be submitted with the protocol for review and 
approval by the IRB/EC. The medical record should include a statement that written informed 
consent was obtained (and should document the date that it was obtained) before the patient is 
enrolled in the study. The original signed consent document will become part of the patient’s medical 
record, a copy will be forwarded to the project manager pursuant to registration, and a copy will be 
sent home with each patient. 
The consent form must include the following information: 
• 
the nature and objectives, potential toxicities, and benefits of the intended study 
• 
the length of therapy and follow-up required 
• 
alternatives to the proposed therapy (including standard and investigational therapies) 
• 
the name of the investigator(s) responsible for the protocol 
• 
the right of the patient to accept or refuse treatment and to withdraw from participation in 
the study at any time 

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11.4 
Protection of Privacy 
Patients will be informed of the extent to which their confidential health information generated from 
this study may be used for research purposes. After this discussion, they will be asked to sign a 
Notice of Privacy Practice research authorization/HIPAA form. This may be embedded within the 
informed consent document. The original signed documents will become part of the patient’s medical 
records, and each patient will receive a copy of the signed documents. The use and disclosure of 
protected health information will be limited to the individuals described in the research 
authorization form. The research authorization form must be prepared by the principal investigator 
and approved by the IRB.  
In compliance with US federal regulations, the investigator is required to permit representatives of 
the US Food and Drug Administration (FDA) or other regulatory authorities to review and/or copy 
any medical records relevant to the study in accordance with local laws. Patients will be informed of 
the extent to which their confidential health information generated from this study may be 
disseminated to other parties. Should direct access to medical records require a waiver or 
authorization separate from the subject’s statement of informed consent, it is the responsibility of the 
investigator to obtain such permission in writing from the patient. 
11.5 
Study Termination or Modification 
Adverse events and laboratory data from this trial will be assessed by the principal investigator 
and/or medical monitor on an ongoing basis. At least quarterly, data from the clinical database will 
be reviewed. The results of this review will be shared with all investigators and MacroGenics  either 
in writing or as part of a teleconference. SAEs will be reviewed as they are reported to the principal 
investigator or project manager, and the medical monitor will make an assessment regarding the 
safety of continuing or modifying the study. This assessment will be shared with the investigators 
either in writing or as part of a teleconference. Should the assessment of either the principal 
investigator or the medical monitor be that the trial should be terminated, the study will then be 
closed to further accrual. Follow-up safety assessments will be performed for all patients who are 
taken out of the study prematurely.

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12. 
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46. Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, et al. B7-H3 and B7x are highly 
expressed in human prostate cancer and associated with disease spread and poor outcome. Proceedings 
of the National Academy of Sciences of the United States of America. 2007 Dec 4;104(49):19458-63. 
47. Zha S, Gage WR, Sauvageot J, et al. Cyclooxygenase-2 is up-regulated in proliferative inflammatory 
atrophy of the prostate, but not in prostate carcinoma. Cancer Res 2001; 61: 8617-8623. 
 
 

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APPENDIX A:  PERFORMANCE STATUS CRITERIA 
            ECOG Performance Status Scale 
              Karnofsky Performance Scale 
Grade 
Description 
% 
Description 
0 
Normal activity. Fully active, able to 
continue all pre-disease performance 
without restriction. 
100 
Normal, no complaints, no evidence of 
disease 
90 
Able to carry on normal activity, minor 
signs or symptoms of disease 
1 
Symptoms, but ambulatory. Restricted in 
physically strenuous activity but 
ambulatory and able to carry out work of 
a light or sedentary nature (e.g., light 
housework, office work). 
80 
Normal activity with effort, some signs or 
symptoms of disease 
70 
Cares for self, unable to carry on normal 
activity or to do active work 
2 
In bed < 50% of the time. Ambulatory 
and capable of all self-care but unable to 
carry out any work activities. Up and 
about more than 50% of waking hours. 
60 
Requires occasional assistance but is able 
to care for most needs 
50 
Requires considerable assistance and 
frequent medical care 
3 
In bed > 50% of the time. Capable of only 
limited self-care, confined to bed or chair  
> 50% of waking hours. 
40 
Disabled, requires special care and 
assistance 
30 
Severely disabled, hospitalization 
indicated. Death not imminent. 
4 
100% bedridden. Completely disabled, 
cannot carry on any self-care, totally 
confined to bed or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes progressing 
rapidly 
5 
Dead 
0 
Dead 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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APPENDIX B:  COMMON TOXICITY CRITERIA, VERSION 4.0 
 
Adverse events will be described and graded using the NCI Common Toxicity Criteria (Version 4.0). 
A copy of this document can be downloaded from the CTEP website (http://ctep.cancer.gov/forms). 
All treatment areas must have a copy of this document, or must be able to access a copy. 
 
In general, the grading system can be summarized as follows: 
 
 
Grade: 
Severity: 
Description: 
Grade 1 
Mild 
Transient or mild discomfort; generally non-progressive; no limitation 
in daily activities; no medical intervention required. 
Grade 2 
Moderate 
Mild/moderate limitation in daily activities; some assistance may be 
required; no/minimal medical intervention required. 
Grade 3 
Severe 
Marked limitation in daily activities; some assistance usually required; 
medical intervention is required. 
Grade 4 
Life-threatening 
Extreme limitation in daily activities; major assistance required; 
significant medical intervention required. 
Grade 5 
Death 
Death related to an adverse event. 
 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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APPENDIX C:  SERIOUS ADVERSE EVENT (SAE) REPORTING FORM 
 
 
Please notify Dr. Emmanuel Antonarakis within 24 hours  
Protocol Title: 
 
 
Neoadjuvant Enoblituzumab (MGA271) in Men with Localized High-Risk 
Prostate Cancer – a Pilot and Biomarker Study 
Protocol 
Number: 
 
 
Principal  
Investigator: 
 
 
Signature  
of PI: 
 
 
 
Date: 
 
 
 
Report Date: 
 
Hospital Admission Date: 
Date of Discovery of 
Event: 
 
 
Report Type: 
  Initial    
  Follow-up 
  Final Follow-up 
  Death 
  Addendum to: 
 
Section A: Subject Information 
Subject ID: 
Subject Initial: 
 
Subject Gender: 
  Male 
  Female 
 
Section B: Event Information 
Event diagnosis or 
symptoms: 
 
Date of MGA271 Dose: 
 
Action taken regarding the study drugs: 
 
 None 
 Interrupted 
 Discontinued 
 
 
Event Onset Date: 
 
Event End Date: 
Relationship to: 
MGA271 
Underlying Disease 
 
Unrelated 
 
 
 
Probably Unrelated 
 
 
 
Possible Related 
 
 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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Probably Related 
 
 
 
Definitely Related 
 
 
 
Section C: Brief Description of the Event: 
 
 
 
 
 
 
 
Section D: Relevant Medical History 
 
 
 
 
Section E: Concomitant Drug (Not related to SAE) 
Name of the Drug 
Start Date 
Stop Date 
Route 
Dose 
Frequency 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section F: Comments 
 
Additional Documents: 
 Please specify  
 
 
 
 
 
 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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APPENDIX D:  ABBREVIATIONS AND ACRONYMS 
ACLS 
Advanced Cardiac Life Support 
ADR 
adverse drug reaction 
ADT 
androgen deprivation therapy 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANOVA 
analysis of variance 
APTT 
activated partial thromboplastin time 
AR 
androgen receptor 
AST 
aspartate aminotransferase 
BCG 
bacillus Calmette-Guerin vaccine 
bid 
bis in die (twice a day) 
BP 
blood pressure 
BSA 
body surface area 
BUN 
blood urea nitrogen 
⁰C 
degrees Celsius 
Ca++ 
calcium 
CBC 
complete blood count 
CD4+ T cells 
cluster determinant 4–positive T lymphocytes 
CD8+ T cells 
cluster determinant 8–positive T lymphocytes 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
Cl− 
chloride 
cm 
centimeter 
COPD 
chronic obstructive pulmonary disease 
CR 
complete response 
CRO 
Clinical Research Office 
CRF 
case report form 
CRPC 
castration resistant prostate cancer 
CRRMC 
Clinical Research Review and Monitoring Committee 
CT 
computerized tomography 
CTL 
Cell Therapy Laboratory 
CTLA-4 
cytotoxic T lymphocyte-associated antigen 4 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DAB 
3,3′-diaminobenzine tetrahydrochloride 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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dL 
deciliter 
DLT 
dose-limiting toxicity 
DMSO 
dimethyl sulfoxide 
DNA 
deoxyribonucleic acid 
DNase 
deoxyribonuclease 
DPBS 
Dubelcco's phosphate buffered saline 
DSMC 
data and safety monitoring committee 
DTH 
delayed-type hypersensitivity 
EC 
ethics committee 
ECOG 
Eastern Cooperative Oncology Group 
EMLA 
eutectic mixture of local anesthetics 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
G-CSF 
granulocyte-colony stimulating factor 
GM-CSF 
granulocyte-macrophage colony-stimulating factor 
GnRH 
gonadotropin-releasing hormone  
HA 
hemagglutinin 
HIPAA 
Health Insurance Portability and Accountability Act 
HR 
heart rate 
HRPC 
hormone-refractory prostate cancer 
HSA 
human serum albumin 
HSB 
hue-saturation-brightness 
IBC 
Institutional Biosafety Committee 
ICH 
International Conference on Harmonisation 
IHC 
Immunohistochemistry 
ID 
intradermal 
IND 
investigational new drug 
INR 
international normalized ratio 
IQR 
interquartile range 
IRB 
Institutional Review Board 
IV 
intravenous 
JHMI 
Johns Hopkins Medical Institutions 
K+ 
potassium 
LDH 
lactate dehydrogenase 
LHRH 
luteinizing hormone releasing hormone 
LNCaP 
AR-positive human prostate cancer cell line derived from a lymph node metastasis 
LOI 
letter of intent 
MedDRA 
Medical Dictionary for Regulatory Activities 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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MTD 
maximum tolerated dose 
NA 
not applicable 
N/A 
not available 
NCI 
National Cancer Institute 
OR 
operating room 
PI 
principal investigator 
PO 
per os (by mouth) 
PSA 
prostate-specific antigen 
PSMA 
prostate-specific membrane antigen 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
qd 
quaque die (every day) 
RP 
radical prostatectomy  
RT 
room temperature 
SAE 
serious adverse event 
SC 
Subcutaneous 
SD 
standard deviation 
SKCCC 
Sidney Kimmel Comprehensive Cancer Center 
TdT 
terminal deoxynucleotidyl transferase 
tid 
ter in die (3 times a day) 
TMA 
tissue microarray  
TRAMP 
transgenic adenocarcinoma of the mouse prostate (mouse model) 
Tregs 
regulatory T lymphocytes 
TUNEL 
TdT-mediated deoxy uridine triphosphate (UTP) nick end-labeling assay 
ULN 
upper limit of normal 
USP 
United States Pharmacopeia (sterile, hypotonic, nonpyrogenic water for injection) 
WBC 
white blood cell 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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APPENDIX E:  DATA AND SAFETY MONITORING PLAN (DSMP) 
 
This is a DSMP Level II study under the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (SKCCC) 
Data Safety Monitoring Plan (DSMP, Version 5.0: 12/6/2012, NCI Approval Date: 12/11/2012).   
 
Data Monitoring of this protocol will occur on a regular basis with the frequency dependent on the rate of 
subject accrual and the progress of the study.  The protocol will be monitored internally at SKCCC by the 
Principal Investigator and externally by the SKCCC CRO in accordance with SKCCC guidelines.  Trial 
monitoring and reporting will be done through the Safety Monitoring Committee (SMC) at SKCCC. 
 
Additionally, scheduled meetings will take place monthly and will include the protocol principal investigator, 
research nurse, data manager, and, when appropriate, the collaborators, sub-investigators, and biostatistician 
involved with the conduct of the protocol. 
 
During these meetings the investigators will discuss matters related to: safety of protocol participants, 
validity and integrity of the data, enrollment rate relative to expectation, characteristics of participants, 
retention of participants, adherence to protocol (potential or real protocol violations), data completeness, and 
progress of data for secondary objectives. 
 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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APPENDIX F: SPECIMEN COLLECTION AND SHIPPING 
 
1. 
Sera for Immunoassays  
 
At each time point (Pre-treatment, Radical Prostatectomy, and Follow-up), the following research blood 
samples should be collected and processed as outlined below:  
 
• Draw approximately 10 mL of peripheral blood into SST (tiger top, i.e. BD Vacutainer Cat #367985) tubes, 
each containing ≥5 mL of blood per vacutainer.  
 
• Allow blood to coagulate for 20 minutes, then centrifuge at 25oC, 1500 x g (2700-3000 rpm), for 15 
minutes.  
 
• Pipette the serum into 10 cryotubes (about 0.5 mL/tube).  
 
• Store cryotubes frozen, below –20oC (–70oC preferred), until the time of analysis. 
 
Please Ping “Vaccine Team” (pager 410-283-0693) and the Immune Core will be notified to pick up the 
sample after draw. 
 
2. 
Peripheral blood lymphocytes (PBLs)  
 
At each time point (Treatment Day 1, Treatment Day 36, and Follow-up day 30), the following research blood 
samples should be collected and processed as outlined below: 
 
• 
Draw approximately 100 mL of peripheral blood into two 50-mL heparinized conical tubes.  
 
• 
PBLs will be prepared by Ficoll-Hypaque density gradient centrifugation according to standard 
protocols 
 
• 
Samples will be cryopreserved in a liquid nitrogen freezer at –140°C for further batched analyses. 
 
Please Ping “Vaccine Team” (pager 410-283-0693) and the Immune Core will be notified to pick up the 
sample after draw. 
 
3. 
Radical Prostatectomy Specimen  
 
All pathologic specimens will be handled in routine fashion by the operating room (OR) staff, except that as 
soon as the specimen is removed the OR nurse will directly page a tissue harvesting technician that is part of 
the Brady Urological Research Institute Prostate Specimen Repository Team. Accessioning of pathology 
specimens will be coordinated in the OR areas by the Departments of Urology and Pathology. A study 
technician will be available to the pathologist receiving the specimen to assure that the tissue is handled 
appropriately for the intended bioassays. At the time of harvesting, the pathologist will apply ink and cut the 
prostate specimen in transverse sections. The specimen will be fixed in 10% phosphate buffered formalin, 
and tissue blocks will be paraffin-embedded and sectioned at 4 μm thickness for routine histologic evaluation 
and for immunohistochemical determinations. Fixation should occur as soon as possible after operative 
removal of the prostate, and ideally within 30-60 minutes. Assessment of index tumors for Gleason grade, 
nodal involvement, and pathologic staging will be conducted in usual fashion and will be provided to the 

A Phase II Trial of Neoadjuvant Enoblituzumab (MGA271) in Men with Localized Intermediate- and High-Risk Prostate Cancer  
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patient for prognostic information. After the pathology report is available, a database will be established and 
all information from the pathology reports of all samples will be included. Tumor blocks and/or additional 
unstained slides will be collected for study-specific quantitative immunohistochemical evaluations. 
 
 Tissue microarrays (TMAs) from formalin-fixed tumor samples will be analyzed for the degree of tumor 
apoptosis using immunohistochemical staining for activated caspase 3 (Marcelli et al 2000), or by using the 
method of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end 
labeling (i.e. TUNEL assay) (Furuya et al 1995). The in situ Cell Death Detection Kit (Roche, Indianapolis, IN) 
may be used to perform TUNEL reactions. Quantification of staining percentage will be achieved using the 
Aperio ScanScope® CS instrument (Aperio Technologies, Vista, CA) as described in Section 8.3.3. This 
endpoint will be expressed as the mean staining percentage in tumor tissue. Analyses will be performed in 
the laboratory of Dr Angelo DeMarzo.  
 
The contact information for the DeMarzo laboratory is listed below: 
Angelo DeMarzo, MD, PhD 
CRB1 - Room 151 
1650 Orleans Street 
Baltimore, MD 21231 
Phone:  (410) 614-5686 
Fax: (410) 502-9817 
Email: ademarz@jhmi.edu