Neoadjuvant AGS-003 Immunotherapy in Patients With Localized Kidney Cancer &lt;pT2
Phase: NA
Conditions: Recurrent Renal Cell Carcinoma, Stage I Renal Cell Cancer, Stage II Renal Cell Cancer
Sponsor: Roswell Park Cancer Institute

5RVZHOO3DUN&DQFHU,QVWLWXWH6WXG\1R,
35,9$7($1'&21),'(17,$/,1)250$7,212)526:(//3$5.&$1&(5,167,787(

3DJHRI

1HRDGMXYDQW$*6,PPXQRWKHUDS\LQ3DWLHQWVZLWK/RFDOL]HG.LGQH\&DQFHUS7
5RVZHOO3DUN&DQFHU,QVWLWXWH
6WXG\1XPEHU ,
,QLWLDO'DWH )HEUXDU\
$PHQGPHQW 0D\
$PHQGPHQW -XO\
$PHQGPHQW 6HSWHPEHU
$PHQGPHQW -DQXDU\
$PHQGPHQW $SULO
$PHQGPHQW -XQH
$PHQGPHQW 0DUFK
3ULQFLSDO,QYHVWLJDWRU 'UPHG7KRPDV6FKZDDE0'
5RVZHOO3DUN&DQFHU,QVWLWXWH
(OP	&DUOWRQ6WUHHWV
%XIIDOR1HZ<RUN

7KRPDV6FKZDDE#5RVZHOO3DUNRUJ
0DQXIDFWXUHU
$UJRV6WXG\5HIHUHQFH1XPEHU
$UJRV7KHUDSHXWLFV,QF
$*6
&RQILGHQWLDOLW\6WDWHPHQW
$Q\ DQG DOO LQIRUPDWLRQ SUHVHQWHGLQ WKLV GRFXPHQW VKDOO EH WUHDWHGDVFRQILGHQWLDODQGVKDOO
UHPDLQWKHH[FOXVLYHSURSHUW\RIWKHSDUW\LHVPHQWLRQHGDERYH7KHXVHRIVXFKFRQILGHQWLDO
LQIRUPDWLRQPXVWEHUHVWULFWHGWRWKHUHFLSLHQWIRUWKHDJUHHGSXUSRVHDQGPXVWQRWEHGLVFORVHG
SXEOLVKHGRURWKHUZLVHFRPPXQLFDWHGWRDQ\XQDXWKRUL]HGSHUVRQVIRUDQ\UHDVRQLQDQ\IRUP
ZKDWVRHYHUZLWKRXWWKHSULRUZULWWHQFRQVHQWRIWKHSDUW\LHVDERYH

Roswell Park Cancer Institute Study No.: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/17 
 
Page 2 of 46 
 
Study Contacts 
Study personnel outside of RPCI-CRS who will be housing essential documents or receiving, 
analyzing or storing biological samples  
Name 
Institution 
Email 
Role 
Tom Maguire 
(919-916-8477) 
Argos Therapeutics, 
Inc. 
Durham, NC 
Fax: 919-287-3416 
Clinicalforms@argostherapeutics.com 
tmaguire@argostherapeutics.com  
Manufacturing 
of AGS003 
from tumor core 
biopsy 
 
Argos Therapeutics, 
Inc. 
 4233 Technology 
Drive, Durham, NC 
27704-2173 
immunomonitoring@argostherapeutics.com 
Immune  
Monitoring 
Dr.med.Thomas 
Schwaab, MD 
(716-845-5770) 
Roswell Park Cancer 
Institute, Buffalo, NY  
Center for Genetics 
and Pharmacology 
(CGP), L5-141 
Lab #: (716-845-7180) 
Thomas.Schwaab@RoswellPark.org 
Correlative 
studies – 
Immune 
Analysis 
Jason Muhitch, 
PhD (716-845-
4930) 
Jason.Muhitch@RoswellPark.org 
Mohammad Habiby 
Kermany, MD PhD 
Mohammad.HabibyKermany@RoswellPark.org 
 
Adaptive 
Biotechnologies, 
Seattle, WA 
(888) 466-8667  
Fax: (650-243-3897) 
clientlservices@adaptivebiotech.com 
Analysis of T-
cell Receptor 
Clonality (pre- 
and post-
treatment. 
 
 
 

Roswell Park Cancer Institute Study No.: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/17 
 
Page 3 of 46 
 
 
SYNOPSIS 
Title  
Neoadjuvant AGS-003 Immunotherapy in Patients with Localized 
Kidney Cancer <pT2 
RPCI Study No. 
I 250113 
RPCI Investigator 
Dr.med.Thomas Schwaab, MD   
Manufacturer 
Argos Therapeutics, Inc. 
4233 Technology Drive 
Durham, NC 27704-2173 
Investigational Study Drug 
AGS-003: A Suspension for Injection, consisting of cryopreserved in vitro 
transcribed (IVT)-RNA-electroporated and cultured autologous mature 
dendritic cells (DCs), formulated in autologous plasma, DMSO and dextrose 
for injection. 
Objectives 
Primary: To assess the immune-modulatory systemic and intratumoral 
effects of AGS-003as neoadjuvant treatment in patients with localized renal 
cell carcinoma. 
Secondary: To assess the feasibility that total tumor RNA processing-
related activities meet specifications for AGS-003 manufacturing utilizing a 
core needle biopsy procedure for tumor harvesting prior to nephrectomy. 
Study Design 
This is a non-randomized single center pilot trial, treating patients who are 
eligible to undergo a partial or radical nephrectomy with the autologous 
AGS-003 immunotherapy in a neoadjuvant fashion prior to surgery. 
Peripheral (blood) and intratumoral parameters will be assessed. 
Target Accrual & Study Duration 
A maximum of 10 patients at RPCI will be enrolled. Study accrual is 
expected to take 4 years. Patients will participate in this study for 
approximately 6 months from the time of consent through final study visit. 
Study Procedures 
Disease Evaluation: Screening. 
Adverse Events assessments: Throughout the study. 
Hematology and Chemistry: Screening, Injection Week #1, Injection Week 
#3, Nephrectomy Visit, and End of Study. 
Autoimmune Assessment: Screening, Injection Week #1, Injection Week 
#3, Nephrectomy Visit, and End of Study. 
Immunologic Analysis Blood Draw: Injection Week #1, Nephrectomy 
Visit, and End of Study. 
Pregnancy Test (urine) in females of childbearing potential: Screening 
and End of Study. 
Performance Status: Screening, Injection Week #1, Injection Week #2, 
Injection Week #3, and End of Study. 
Physical Examination: Screening and End of Study. 
Tumor biopsy for manufacture of AGS-003: Screening. 
Leukapheresis for manufacture of AGS-003: Leukapheresis Visit (must 
be at least 48 hours between tumor biopsy and leukapheresis) 
AGS-003 Dosing: Once-weekly dosing beginning at Injection Week #1 for 

Roswell Park Cancer Institute Study No.: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/17 
 
Page 4 of 46 
 
3 weeks. 
Statistical Analysis 
Sample Size Determination: A maximum of 10 patients will be enrolled in 
this study. 
The primary objective of this study is to assess immune-modulatory systemic 
and intratumoral effects of AGS-003 as neoadjuvant treatment in patients 
with localized renal cell carcinoma. 
Peripheral blood samples for immunological analysis will be collected 
before the first dose of AGS-003, after the 3rd dose of AGS-003, and at the 
end of the study. The time component will be modeled as a three-level 
classification factor. The full model for the effects of injection mode and 
time will be fit using Linear Mixed Model methods. The model will include 
a random patient effect and five fixed effects for time, and the interactions. 
The presence of any time effect will be assessed with full-reduced model 
Type 3 test. If the omnibus test is statistically significant at the p < 0.05 
level, then three pairwise time-point comparisons will be conducted. 
Safety Analysis: Adverse event rates will be summarized in all patients who 
receive at least 1 or more doses of AGS-003. These rates will be described as 
the proportion of patients with the event, by grade, and supported with exact 
95% confidence intervals. 
Stopping Rule: If during the trial 4 or more patients experience the 
undesirable event defined as unexpected bleeding or more difficult than 
usual perinephric dissection, accrual will be halted and the treatment will be 
deemed unsafe. 
Correlative Data Analysis: Peripheral blood immune cell populations will 
be analyzed using flow cytometry, ELISA, and ELISPOT assays. Tumor 
tissue will be processed and analyzed using flow cytometric and 
immunohistochemical methods. 

5RVZHOO3DUN&DQFHU,QVWLWXWH6WXG\1R,
35,9$7($1'&21),'(17,$/,1)250$7,212)526:(//3$5.&$1&(5,167,787(

3DJHRI
,19(67,*$725678'<(/,*,%,/,7<9(5,),&$7,21)250
3DWLHQW1DPHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
0HGLFDO5HFRUG1RBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
7LWOH,1HRDGMXYDQW$*6,PPXQRWKHUDS\LQ3DWLHQWVZLWK/RFDOL]HG.LGQH\
&DQFHUS7
,1&/86,21&5,7(5,$
<HV
1R
1$
$OODQVZHUVPXVWEH³<HV´RU³1$´IRUSDWLHQWHQUROOPHQW
'DWH


 $JH\HDUVRIDJH



 +DYHORFDOL]HGQRQPHWDVWDWLF5&&S7102DVSHUWKH$-&&WK
HGLWLRQFULWHULD3DWLHQWVZKRKDYHQRWKDGDELRSV\PXVWKDYHDVROLG
UHQDO PDVV VXJJHVWLYH RI 5&& ZLWK FRQILUPDWLRQ RI 5&& DW VFUHHQLQJ
ELRSV\



 0XVWEHVXUJLFDOFDQGLGDWHVDVGHHPHGILWE\VXUJHRQ



 3DWLHQWV RI FKLOGEHDULQJ SRWHQWLDO PXVW DJUHH WR XVH DGHTXDWH
FRQWUDFHSWLYHPHWKRGVHJKRUPRQDORUEDUULHUPHWKRGRIELUWKFRQWURO
DEVWLQHQFHSULRUWRVWXG\HQWU\DQGIRUWKHGXUDWLRQRIVWXG\SDUWLFLSDWLRQ
6KRXOGDZRPDQEHFRPHSUHJQDQWRUVXVSHFWVKHLVSUHJQDQWZKLOHVKHRU
KHUSDUWQHULVSDUWLFLSDWLQJLQWKLVVWXG\VKHVKRXOGLQIRUP WKHWUHDWLQJ
SK\VLFLDQLPPHGLDWHO\



 :LOOLQJQHVV WR XQGHUJR OHXNDSKHUHVLV DQG ELRSV\ SURFHGXUHV IRU WKH
DXWRORJRXVFRPSRQHQWVLHSHULSKHUDOEORRGPRQRQXFOHDUFHOOVSODVPD
DQG IUHVK WXPRU VSHFLPHQ UHTXLUHG IRU PDQXIDFWXUH RI $*6
LPPXQRWKHUDS\




3DWLHQWRUOHJDOUHSUHVHQWDWLYHPXVWXQGHUVWDQGWKHLQYHVWLJDWLRQDOQDWXUH
RI WKLV VWXG\ DQG VLJQ DQ ,QGHSHQGHQW (WKLFV &RPPLWWHH,QVWLWXWLRQDO
5HYLHZ%RDUGDSSURYHGZULWWHQLQIRUPHGFRQVHQWIRUPSULRUWRUHFHLYLQJ
DQ\VWXG\UHODWHGSURFHGXUH
,QYHVWLJDWRU6LJQDWXUHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB'DWHBBBBBBBBBBBBB


5RVZHOO3DUN&DQFHU,QVWLWXWH6WXG\1R,
35,9$7($1'&21),'(17,$/,1)250$7,212)526:(//3$5.&$1&(5,167,787(

3DJHRI
,19(67,*$725678'<(/,*,%,/,7<9(5,),&$7,21)250
3DWLHQW1DPHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
0HGLFDO5HFRUG1RBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
7LWOH,1HRDGMXYDQW$*6,PPXQRWKHUDS\LQ3DWLHQWVZLWK/RFDOL]HG.LGQH\
&DQFHUS7
(;&/86,21&5,7(5,$
<HV
1R
1$
$OODQVZHUVPXVWEH³1R´RU³1$´IRUSDWLHQWHQUROOPHQW
'DWH



 3DWLHQWV ZKR KDYH KDG FKHPRWKHUDS\ RU UDGLRWKHUDS\ ZLWKLQ ZHHNV
ZHHNVIRUQLWURVRXUHDVRUPLWRP\FLQ&SULRUWRHQWHULQJWKHVWXG\RU
WKRVH ZKR KDYH QRW UHFRYHUHG IURP DGYHUVH HYHQWV GXH WR DJHQWV
DGPLQLVWHUHGPRUHWKDQZHHNVHDUOLHU




 8QFRQWUROOHGLQWHUFXUUHQWLOOQHVVLQFOXGLQJEXWQRWOLPLWHGWRRQJRLQJRU
DFWLYHLQIHFWLRQV\PSWRPDWLFFRQJHVWLYHKHDUWIDLOXUHHJVKRUWQHVVRI
EUHDWK IDWLJXH RUWKRSQHD SDUR[\VPDO QRFWXUQDO G\VSQHD XQVWDEOH
DQJLQD SHFWRULV FDUGLDF DUUK\WKPLD RU SV\FKLDWULF LOOQHVVVRFLDO
VLWXDWLRQVWKDWZRXOGOLPLWFRPSOLDQFHZLWKVWXG\UHTXLUHPHQWV




 5DGLDWLRQWRSULPDU\WXPRUSULRUWRHQUROOPHQWLQWKLVVWXG\




 3UHJQDQWRUQXUVLQJIHPDOHSDWLHQWV




 8QZLOOLQJRUXQDEOHWRIROORZSURWRFROUHTXLUHPHQWV




 $FWLYH
DXWRLPPXQH
GLVHDVH
RU
FRQGLWLRQ
UHTXLULQJ
FKURQLF
LPPXQRVXSSUHVVLYH WKHUDS\ HJ UKHXPDWRLG DUWKULWLV V\VWHPLF OXSXV
HU\WKHPDWRXVPXOWLSOHVFOHURVLVRUJDQWUDQVSODQWUHFLSLHQWHWF
x
127($EQRUPDOODERUDWRU\YDOXHVIRUDXWRLPPXQLW\PDUNHUV
LQWKHDEVHQFHRIRWKHUVLJQVV\PSWRPVRIDXWRLPPXQHHGLVHDVH
DUHQRWH[FOXVLRQDU\




 .QRZQ
FOLQLFDOO\
VLJQLILFDQW
LQIHFWLRQV
LQFOXGLQJ
KXPDQ
LPPXQRGHILFLHQF\YLUXV+,9DQGDFWLYHKHSDWLWLV%RU&




 $Q\FRQGLWLRQZKLFKLQWKH,QYHVWLJDWRU¶VRSLQLRQGHHPVWKHSDWLHQWDQ
XQVXLWDEOH FDQGLGDWH WR UHFHLYH WUHDWPHQW LH DQ\ VLJQLILFDQW PHGLFDO
LOOQHVV RU DEQRUPDO ODERUDWRU\ ILQGLQJ WKDW ZRXOG LQ WKH LQYHVWLJDWRU¶V
MXGJPHQWLQFUHDVHWKHVXEMHFW¶VULVNE\SDUWLFLSDWLQJLQWKLVVWXG\




 &KURQLFXVHRIV\VWHPLFFRUWLFRVWHURLGVLHPJGD\SUHGQLVRQHRU
HTXLYDOHQW




 5HFHLYHGDQLQYHVWLJDWLRQDODJHQWZLWKLQGD\VSULRUWRHQUROOPHQW

3DWLHQWPHHWVDOOHQWU\FULWHULD

<HV
1R
,QYHVWLJDWRU6LJQDWXUHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
'DWHBBBBBBBBBB

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 7 of 46 
 
TABLE OF CONTENTS 
1 
BACKGROUND ........................................................................................................11 
1.1 
RENAL CELL CARCINOMA ...................................................................................11 
1.2 
AGS-003 PRODUCT SUMMARY ............................................................................11 
1.3 
PHARMACEUTICAL PROPERTIES OF AGS-003 ................................................12 
1.4 
CLINICAL STUDIES WITH AGS-003 ....................................................................13 
1.5 
CLINICAL IMMUNO-DYNAMICS OF AGS-003 MONOTHERAPY ...................13 
1.6 
AGS-003 SAFETY .....................................................................................................14 
2 
RATIONALE .............................................................................................................14 
3 
OBJECTIVES .............................................................................................................15 
3.1 
PRIMARY OBJECTIVE ............................................................................................15 
3.2 
SECONDARY OBJECTIVE......................................................................................15 
4 
METHODOLOGY .....................................................................................................15 
4.1 
STUDY DESIGN .......................................................................................................15 
4.2 
TARGET ACCRUAL AND STUDY DURATION...................................................15 
5 
PATIENT SELECTION .............................................................................................16 
5.1 
INCLUSION CRITERIA ...........................................................................................16 
5.2 
EXCLUSION CRITERIA ..........................................................................................16 
5.3 
INCLUSION OF WOMEN AND MINORITIES ......................................................17 
6 
TREATMENT PLAN .................................................................................................17 
6.1 
STUDY PROCEDURES FOR MANUFACTURE OF AGS-003 .............................17 
 
TUMOR SPECIMEN FOR AGS-003 ........................................................................17 
6.1.1
 
LEUKAPHERESIS ....................................................................................................18 
6.1.2
6.2 
DOSING AND ADMINISTRATION ........................................................................18 
 
INTRADERMAL INJECTION ..................................................................................18 
6.2.1
6.3 
DOSE MODIFICATIONS .........................................................................................19 
6.4 
GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE ..........19 
 
PERMITTED MEDICATIONS .................................................................................19 
6.4.1
 
PROHIBITED MEDICATIONS ................................................................................20 
6.4.2
 
DRUG INTERACTIONS ...........................................................................................20 
6.4.3

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 8 of 46 
 
6.5 
TREATMENT DISCONTINUATION ......................................................................20 
7 
INVESTIGATIONAL PRODUCT ............................................................................21 
7.1 
ACTIVE SUBSTANCE AND SOURCE ...................................................................21 
7.2 
RISKS/BENEFITS OF AGS-003 ...............................................................................21 
7.3 
PACKAGING AND LABELING ..............................................................................22 
7.4 
DRUG SHIPMENT ....................................................................................................22 
 
AGS-003 CRYOSHIPPER SYSTEM ........................................................................22 
7.4.1
 
STUDY DRUG SHIPMENTS FROM ARGOS .........................................................22 
7.4.2
7.5 
DOSE PREPARATION AND ADMINISTRATION ................................................23 
 
INJECTION SITE REACTIONS ...............................................................................24 
7.5.1
7.6 
HANDLING AND DISPOSAL .................................................................................24 
8 
STUDY PROCEDURES ............................................................................................24 
8.1 
PATIENT REGISTRATION......................................................................................24 
8.2 
SCREENING ..............................................................................................................24 
8.3 
LEUKAPHERESIS VISIT (MUST OCCUR WITHIN 3 WEEKS AFTER 
BIOPSY) .....................................................................................................................25 
8.4 
AGS-003 TREATMENT PHASE ..............................................................................26 
 
INJECTION WEEK #1 ..............................................................................................26 
8.4.1
 
INJECTION WEEK #2 ..............................................................................................26 
8.4.2
 
INJECTION WEEK #3 ..............................................................................................26 
8.4.3
 
NEPHRECTOMY VISIT ...........................................................................................26 
8.4.4
8.5 
END OF STUDY VISIT/ FOLLOW-UP ...................................................................27 
8.6 
SCHEDULE OF PROCEDURES AND OBSERVATIONS .....................................27 
9 
BIOLOGICAL SPECIMEN MANAGEMENT .........................................................30 
9.1 
BLOOD SAMPLE COLLECTION AND PROCESSING FOR 
IMMUNOLOGIC ANALYSIS ..................................................................................30 
 
SAMPLES FOR ARGOS IMMUNE MONITORING ...............................................30 
9.1.1
 
SAMPLES FOR CORRELATIVE STUDIES ...........................................................30 
9.1.2
9.2 
LEUKAPHERESIS ....................................................................................................31 
9.3 
NEPHRECTOMY ......................................................................................................31 
9.4 
PATHOLOGY ............................................................................................................32 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 9 of 46 
 
 
PRE-TREATMENT FORMALIN-FIXED PARAFFIN EMBEDDED 
9.4.1
(FPPE) BIOPSY SAMPLES ......................................................................................32 
 
POST-TREATMENT RESECTION FORMALIN-FIXED PARAFFIN 
9.4.2
EMBEDDED (FPPE) SAMPLES ..............................................................................32 
10 
SAFETY EVALUATION ..........................................................................................33 
10.1 
MEDICAL HISTORY ................................................................................................33 
10.2 
PHYSICAL EXAMINATION ...................................................................................33 
10.3 
AUTOIMMUNITY ASSESSMENTS ........................................................................33 
10.4 
INJECTION SITE REACTION AND POST-DOSE VITAL SIGNS 
EVALUATION ..........................................................................................................34 
10.5 
ADVERSE EVENTS..................................................................................................34 
 
DEFINITION ..............................................................................................................34 
10.5.1
 
DIAGNOSIS VERSUS SIGNS AND SYMPTOMS .................................................34 
10.5.2
 
ADVERSE EVENTS OCCURRING SECONDARY TO OTHER EVENTS...........35 
10.5.3
 
ABNORMAL LABORATORY VALUES ................................................................35 
10.5.4
 
PREEXISTING MEDICAL CONDITIONS (BASELINE CONDITIONS) .............35 
10.5.5
10.6 
GRADING AND RELATIONSHIP TO DRUG ........................................................35 
10.7 
REPORTING ADVERSE EVENTS ..........................................................................36 
10.8 
SERIOUS ADVERSE EVENTS ................................................................................37 
 
DEFINITION ..............................................................................................................37 
10.8.1
 
REPORTING SERIOUS ADVERSE EVENTS ........................................................37 
10.8.2
 
INVESTIGATOR REPORTING: NOTIFYING THE AGS-003 
10.8.3
MANUFACTURER ...................................................................................................37 
 
FOLLOW-UP FOR SERIOUS ADVERSE EVENTS ...............................................38 
10.8.4
10.9 
UNANTICIPATED PROBLEMS ..............................................................................38 
 
DEFINITION ..............................................................................................................38 
10.9.1
 
REPORTING UNANTICIPATED PROBLEMS .......................................................38 
10.9.2
10.10 
FDA REPORTING .....................................................................................................38 
10.11 
GENE THERAPY STUDY REPORTING OF SERIOUS ADVERSE 
EVENTS .....................................................................................................................39 
11 
DATA AND SAFETY MONITORING .....................................................................40 
12 
STATISTICAL METHODOLOGY ...........................................................................40 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 10 of 46 
 
12.1 
SAMPLE SIZE DETERMINATION .........................................................................41 
12.2 
EFFICACY ANALYSIS ............................................................................................41 
12.3 
SAFETY ANALYSIS ................................................................................................41 
12.4 
STOPPING RULE: .....................................................................................................41 
12.5 
INTERIM ANALYSIS AND CRITERIA FOR EARLY TERMINATION 
OF THE STUDY ........................................................................................................42 
13 
CORRELATIVE DATA ANALYSIS ........................................................................42 
14 
ETHICAL AND REGULATORY STANDARDS ....................................................42 
14.1 
ETHICAL PRINCIPLES ............................................................................................42 
14.2 
INFORMED CONSENT ............................................................................................43 
15 
STUDY RESPONSIBILITIES ...................................................................................43 
15.1 
DATA COLLECTION ...............................................................................................43 
15.2 
MAINTENANCE OF STUDY DOCUMENTS .........................................................44 
16 
ADMINISTRATIVE RULES ....................................................................................44 
16.1 
REVISIONS TO THE PROTOCOL ..........................................................................44 
16.2 
TERMINATION OF THE STUDY ...........................................................................44 
16.3 
CONFIDENTIALITY ................................................................................................44 
17 
APPENDICES ............................................................................................................45 
18 
REFERENCES ...........................................................................................................46 
 
IN-TEXT TABLES 
Table 1. 
Schedule of Procedures and Observations ..................................................................28 
Table 2. 
Guidelines for Routine Adverse Event Reporting for Pilot Studies 
(Regardless of Expectedness) .....................................................................................36 
 
APPENDICES 
Appendix A ECOG Performance Status Scores .........................................................................45 
 
 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 11 of 46 
 
1 
BACKGROUND 
1.1 
Renal Cell Carcinoma 
Renal Cell Carcinoma (RCC) is the most lethal urologic cancer. Up to 30% of patients will 
present with metastatic disease. RCC is one of the few solid malignancies with continuously 
rising incidence over the past decade(2). Up to 40% of patients who undergo partial or radical 
nephrectomy for clinically localized RCC will recur as metastatic disease. High-dose 
Interleukin-2 (HD IL-2) is the only FDA-approved treatment with curative and long lasting 
results (3, 4). However, toxicities are high because HD IL-2 based immunotherapy is a non-
specific immunostimulant leading to severe autoimmune reactions. There is a need for more 
tumor-specific immunotherapies to avoid these autoimmune toxicities in this highly immune-
reactive cancer. Immunotherapy research has focused on identifying a more targeted approach by 
identifying and utilizing tumor-specific antigens. 
1.2 
AGS-003 Product Summary 
Refer to Argos Therapeutics, Inc. AGS-003 Investigator’s Brochure for more information on 
AGS-003, including Pharmacology, Immunologic Activity, Potency, Toxicology, and Safety. 
Argos Therapeutics, Inc. (Argos) is an immunotherapy company with corporate headquarters in 
Durham, NC, and is the manufacturer of AGS-003. AGS-003 is an autologous active cellular 
immunotherapy designed to activate specific T cells that will assist in identifying and attacking 
unique antigens found on each subject’s own tumor cells. AGS-003 utilizes autologous dendritic 
cells (DCs) co-electroporated with ribonucleic acids (RNAs) encoding autologous RCC antigens 
(derived from the patient’s tumor biopsy specimen) and synthetically derived CD40L (CD40 is a 
glycoprotein expressed by DCs and DC maturation and T cell activation is significantly 
improved by CD40L stimulation.). The autologous precursor components for AGS-003 are 
biopsy-derived tumor specimen and leukocytes obtained via leukapheresis. 
Tumor specimens collected from the subject during the biopsy procedure are placed in a 
formaldehyde-free, RNA preservative solution and shipped for next day delivery to Argos. In an 
aseptic processing area at Argos, tumor RNA is isolated from the specimen. Total cellular RNA 
is amplified via reverse transcriptase (RT) polymerase chain reaction (PCR) and the resulting 
complimentary deoxyribonucleic acid (cDNA), highly enriched for copies of messenger RNA 
(mRNA) from the original tumor specimen, is purified. The cDNA is used to generate and 
further amplify RNA using an in vitro transcribed (IVT) system. Thus, RNA encoding 
potentially all of the patient’s tumor sample antigens is amplified for electroporation. 
Leukocytes are obtained from subjects by leukapheresis using standard institutional procedures 
in accordance to Argos collection parameters, and are express shipped to the Argos facility. At 
the Argos facility, DC precursors (monocytes) are isolated from the leukocytes in the aseptic 
processing area by elutriation and are cultured to achieve DC maturation. 
Post-maturation, DCs are electroporated with autologous amplified tumor and CD40L RNA. 
After RNA electroporation, the DCs are cultured to generate the final cellular preparation. This 
production method is known as the post-maturation electroporation (PME) -CD40L process. The 
resulting RNA-electroporated mature DCs are suspended in autologous plasma, 10% dextrose for 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 12 of 46 
 
injection, and 10% dimethyl sulfoxide (DMSO), for cryopreservation, to comprise the finished 
product and frozen for storage until use. 
All manufacturing and storage of the AGS-003 product is performed under current Good 
Manufacturing Practices (cGMP) by Argos. The final cGMP product is released for clinical use 
only if it passes all quality control testing, including tests for potency, sterility, and (absence of) 
endotoxin and mycoplasma. 
Dendritic cells are antigen presenting cells (APCs) that can stimulate cell-mediated immunity 
through effects on both CD4+ and CD8+ T cells. The current hypothesis for the AGS-003 product 
is that the autologous RNA-electroporated DCs present tumor antigens to both memory and 
naive or resting T cells resulting in an expanded antigen-specific immune response. 
It has been previously demonstrated that a typical adaptive immune response requires the 
integration of 3 signals: 1.) the major histocompatibility complex (MHC)/antigenic peptide 
interaction, 2.), the engagement of co-stimulatory molecules such as CD80 and CD86 and, 
3.) the intercellular activity of IL-12 (5). AGS-003 incorporates all 3 of these signals in a single 
cellular product, enabling an adaptive immune response in RCC subjects who are otherwise 
immunocompromised (6). 
In RCC, the normal immune surveillance function is thought to be compromised by the 
recruitment of regulatory T cells that suppress the anti-tumor response (7). When used as a 
single-agent, AGS-003 reversed tumor-induced immunosuppression in a majority of subjects 
tested (AGS-003-004). This was evident by the restoration of IFN-γ secretion by T cells isolated 
from subjects receiving AGS-003. 
1.3 
Pharmaceutical Properties of AGS-003 
AGS-003 is an autologous dendritic cell immunotherapy. It consists of DCs co-electroporated 
with amplified autologous tumor RNA and CD40L RNA. The autologous tumor RNA is used to 
direct the immune response to the subject’s tumor. The CD40L RNA is used to induce secretion 
of IL-12 leading to activation of effector memory cytotoxic T lymphocytes (CTLs). A strong 
correlation between IL-12 and the induction of effector memory CTLs has been demonstrated 
(8). Therefore, the potency of AGS-003 is in part determined by secretion of IL-12 from the 
cellular product (DCs after electroporation and culture). IL-12 plays a role in the induction of 
multi-functional effector memory CTLs and is considered a marker of immune cell 
differentiation. 
Dendritic cell-based immunotherapeutics must induce robust CTLs capable of killing tumor in 
vivo if they are to be clinically effective. Argos has shown that AGS-003 generates high-avidity 
CTLs in vitro that lyse cells that express naturally processed and presented tumor antigen (Ag). 
Unlike cytokine cocktail-matured DCs, which induce predominantly non-proliferative effector 
memory CD45RA+ CTLs, AGS-003 primes a novel subset of antigen-specific CTLs that can be 
expanded to large numbers upon sequential DC stimulation in vitro. Argos has defined these 
cells as REHA (rapidly expanding high avidity) CTLs based on: 1.) the maintenance of CD28 
expression, 2.) production of high levels of IFN-γ and IL-2 in response to Ag and, 3.) the 
demonstration of high-avidity T cell receptors (TCRs) that exhibit strong cytolytic activity 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 13 of 46 
 
toward limiting amounts of native Ag (9). These results suggest that AGS-003 DCs, consistent 
with their ability to express IL-12, are uniquely capable of delivering the complex array of 
signals needed to generate stable CD28+/CD45RA- REHA CTLs, which, if generated in vivo, 
could be clinically beneficial for treatment of metastatic RCC. In support of this hypothesis, 
clinical immune monitoring results from the AGS-003-004 study showed that AGS-003 induces 
polyclonal CTL response to tumor antigens and that a subset of responding T cells secrete the 
cytokines IFN-γ and IL-2, suggesting an effector memory or central memory phenotype. 
1.4 
Clinical Studies with AGS-003 
AGS-003 is the second-generation product based on the proprietary Arcelis™ technology for 
producing RNA-electroporated DCs for cancer immunotherapy. The first-generation product, 
MB-002, was virtually identical to AGS-003 in its autologous components, but did not include 
synthetically derived CD40L RNA nor did it utilize the sequential DC maturation process. The 
purpose of adding this CD40L RNA is to provide the CD40/CD40L ligation signal required by 
the DCs to induce IL-12 secretion (10). IL-12 has been demonstrated to be linked to the 
functionality of the DC (8), and assessment of IL-12 secreted from the DC product serves as a 
potency marker for the release of the AGS-003 product. 
To date, in over 6 years of clinical experience, a total of 63 newly diagnosed, unfavorable risk 
subjects with metastatic RCC received a total of over 500 doses of either AGS-003 or MB-002 in 
Phase I/II and Phase II studies, with dosing of multiple years’ duration for some subjects. The 
first 2 clinical trials, MB-002-003 and AGS-003-004, were open-label, single-arm studies of 
MB-002 and AGS-003, respectively, as first-line monotherapy in subjects with advanced RCC. 
The third trial, AGS-003-006, was a single-arm Phase II study that used a combination therapy 
of AGS-003 plus sunitinib in previously untreated subjects with advanced RCC. Both safety and 
efficacy results from these studies have been encouraging. 
A Phase III trial, AGS-003-007, is ongoing in patients with advanced RCC. This is a randomized 
trial that will compare the safety and efficacy of AGS-003 plus standard treatment versus 
standard treatment alone. For both study arms, standard treatment will begin with sunitinib 
(administered per current product labeling, and initiating with 50 mg/day for 4 weeks followed 
by a 2 week drug-free period each cycle, unless indicated otherwise by current labeling). 
1.5 
Clinical Immuno-dynamics of AGS-003 Monotherapy 
In all clinical studies of AGS-003 and the predecessor product MB-002, blood samples collected 
from subjects at defined points on study have been assessed for monitoring of immune function. 
In Study MB-002-003, 8 of 12 subjects that were evaluable for immune monitoring recovered 
some measure of immunocompetency after treatment and their T cells were able to mount an 
IL-2 immune response to more than one stimulus. However, immune response monitoring 
indicated this first generation product (MB-002) did not fully overcome the apparent immune 
deficiency in RCC subjects (notably, although the IL-2 response was rescued, no restoration of 
IFN-γ responses was observed). 
For study AGS-003-004, as a measure of general immune system health, the total response to 
DC re-stimulation was analyzed at 4 time points: two before treatment and two post-treatment. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 14 of 46 
 
The majority of study subjects exhibited increased immune responsiveness to a variety of 
immunogens after AGS-003 therapy, which may indicate general immune reconstitution since 
some test immunogens were not part of the AGS-003 RNA payload. Overall, 12 of 16 subjects 
(75%) had a response over post-treatment to at least one of the tumor antigens [refer to 
Investigator’s Brochure (IB)], suggesting that RCC subject T cells can mount a polyclonal 
response to multiple antigens associated with their own tumors when antigen is encoded as RNA 
that is electroporated into DCs matured with the PME-CD40L process. A subset of the T cell 
response was associated with T cells bearing both IFN-γ and IL-2. This profile is associated with 
T cells exhibiting “effector memory” and/or “central memory” activities (9).The hallmark of 
effective immune therapy is the induction of “immunological memory”. 
1.6 
AGS-003 Safety 
Previous clinical studies have demonstrated that single-agent AGS-003 and its predecessor 
product MB-002 are safe and well-tolerated. With more than 500 doses delivered across these 
studies, most drug-related adverse events (AEs) have been mild to moderate injection site 
reactions, with no reports of any drug-related AEs with Grade 3 or Grade 4 toxicity, and no drug-
related serious adverse events (SAEs). No subjects in any studies of AGS-003 or MB-002 have 
developed autoimmune disease, and periodic assessments of autoimmunity markers in these 
studies have yielded no clinically significant findings. Of note, in all RCC studies each subject 
received AGS-003 manufactured from the subject’s tumor (primary or metastatic RCC site), yet 
no subjects developed autoimmune reactions against their remaining (healthy) kidney. 
2 
RATIONALE 
Dendritic cells (DC) are the most potent cells in initiating antigen-specific T cell responses. In 
particular, they are key players in the initiation of so-called cross presentation. Cross 
presentation is crucial for the induction of both CD8 cytotoxic T cells and CD4 memory T cells 
to initiate a memory immune response. The clinical and immunologic potential of an autologous 
DC immunotherapy was demonstrated in a recent Phase II trial (11). Patients with metastatic 
kidney cancer received an autologous, tumor-lysate pulsed DC vaccine and showed a median 
progression free survival (PFS) of 8 months. The median OS has not been reached. Nine 
objective responses were noted (50%; 95% CI 22%-66%), which included complete responses in 
2 patients (19 and 24 months) and 7 partial responses (3-9 months). This trial demonstrated that 
an autologous DC vaccine can be prepared in a consistent, high-quality fashion (11). Autologous 
tumor lysate provides a large number of target antigens, but it requires a large volume of tumor 
tissue. Of particular importance, tumor specimen obtained from reduced quantity of starting 
tumor tissue, such as from a core needle biopsy procedure, should routinely provide sufficient 
total tumor RNA to initiate the RNA amplification process, making available ample source 
material for dendritic cell transfection. AGS-003 combines the most up-to-date DC vaccine 
technology with the option of targeting a plethora of autologous, tumor-specific target antigens. 
The data on the clinical efficacy of AGS-003 is becoming increasingly apparent, however, the 
direct anti-tumor mechanism of action is as of yet undefined. The proposed research study will 
analyze this mechanism of action. In addition, this neoadjuvant concept of preoperative AGS-
003 immunotherapy will lead to better understanding of the role of neoadjuvant immunotherapy 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 15 of 46 
 
as a means to potentially facilitate tumor resections and may even provide the option of 
“downsizing” a kidney tumor and change the surgical approach from radical to partial 
nephrectomy, thus providing significant preservation of precious renal function. If this proposed 
study demonstrates the expected systemic and intratumoral immune responses, it will lead to the 
design of a larger Phase II study. 
3 
OBJECTIVES 
3.1 
Primary Objective 
• To assess the immune-modulatory systemic and intratumoral effects of AGS-003 as 
neoadjuvant treatment in patients with localized renal cell carcinoma. 
3.2 
Secondary Objective 
• To assess the feasibility that total tumor RNA processing-related activities meet 
specifications for AGS-003 manufacturing utilizing a core needle biopsy procedure 
for tumor harvesting prior to nephrectomy (see Argos “Summary of Experience with 
RNA Amplification from Various Types of Primary Tumors”). 
4 
METHODOLOGY 
4.1 
Study Design 
This is a non-randomized, single center Pilot study treating patients with non-metastatic RCC 
with the autologous dendritic cell AGS-003 as a neoadjuvant treatment prior to extirpative 
radical or partial nephrectomy. 
Eligible patients will be administered the AGS-003 as a single, fixed dose of 1.2 x 107  DCs, 
delivered as an intradermal injection (0.6 mL per dose delivered as three separate 0.2 mL 
injections per full dose) once weekly for a total of 3 doses beginning at Injection Week #1, 
followed by a partial or radical nephrectomy at the Nephrectomy Visit. Blood will be taken for 
immunological analysis at the time of the first dose, after the 3rd dose, and at End of Study. 
All patients will sign an informed consent prior to study related tests. All patients will meet the 
inclusion and exclusion criteria. Patients will be treated on an outpatient basis. Kidney surgery 
will require inpatient admission postoperatively. 
4.2 
Target Accrual and Study Duration 
A maximum of 10 patients at RPCI will be enrolled. Study accrual is expected to take 4 years. 
Patients will participate in this study for approximately 6 months from the time of consent 
through the final study visit. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 16 of 46 
 
5 
PATIENT SELECTION 
5.1 
Inclusion Criteria 
To be included in this study, patients must meet the following criteria: 
1. Age ≥ 18 years of age. 
2. Have localized non-metastatic RCC (<pT2, NO, MO), as per the AJCC 7th edition 
criteria(1). Patients who have not had a biopsy must have a solid renal mass suggestive of 
RCC with confirmation of RCC at screening biopsy. 
3. Must be surgical candidates as deemed fit by surgeon. 
4. Patients of child-bearing potential must agree to use adequate contraceptive methods 
(e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 
the duration of study participation. Should a woman become pregnant or suspect she is 
pregnant while she or her partner is participating in this study, she should inform the 
treating physician immediately. 
5. Willingness to undergo leukapheresis and biopsy procedures for the autologous 
components (peripheral blood mononuclear cells, plasma and fresh tumor specimen) 
required for manufacture of AGS-003. 
6. Patient or legal representative must understand the investigational nature of this study and 
sign an Independent Ethics Committee/Institutional Review Board approved written 
informed consent form prior to receiving any study related procedure. 
5.2 
Exclusion Criteria 
Patients will be excluded from this study for the following: 
1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for 
nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered 
from adverse events due to agents administered more than 4 weeks earlier. 
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, 
symptomatic congestive heart failure (e.g., shortness of breath, fatigue, orthopnea, 
paroxysmal nocturnal dyspnea), unstable angina pectoris, cardiac arrhythmia, or 
psychiatric illness/social situations that would limit compliance with study requirements. 
3. Radiation to primary tumor prior to enrollment in this study. 
4. Pregnant or nursing female patients. 
5. Unwilling or unable to follow protocol requirements. 
6. Active autoimmune disease or condition requiring chronic immunosuppressive therapy 
(e.g., rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ 
transplant recipient, etc.). 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 17 of 46 
 
o NOTE: Abnormal laboratory values for autoimmunity markers in the absence of 
other signs/symptoms of autoimmune disease are not exclusionary. 
7. Known clinically significant infections, including human immunodeficiency virus (HIV) 
and active hepatitis B or C 
8. Any condition which in the Investigator’s opinion deems the patient an unsuitable 
candidate to receive treatment (i.e., any significant medical illness or abnormal laboratory 
finding that would, in the investigator’s judgment, increase the subject’s risk by 
participating in this study). 
9. Chronic use of systemic corticosteroids (i.e., ≥ 10 mg/day prednisone or equivalent). 
10. Received an investigational agent within 30 days prior to enrollment. 
5.3 
Inclusion of Women and Minorities 
Both men and women and members of all races and ethnic groups are eligible for this study. 
6 
TREATMENT PLAN 
6.1 
Study Procedures for Manufacture of AGS-003 
AGS-003 will be manufactured using autologous specimens obtained from the procedures 
described below. As described below, tumor specimens obtained by percutaneous biopsy will be 
collected for all study subjects at Screening. Also, as described below, peripheral blood 
mononuclear cells (PBMCs) and plasma will be collected by leukapheresis. 
The autologous starting materials for the AGS-003 product are peripheral blood mononuclear 
cells (PBMCs) obtained by leukapheresis, RCC tissue obtained from a core needle biopsy, and 
plasma obtained with the PBMCs during leukapheresis. These components are then shipped 
directly to Argos for manufacturing at a centralized facility under current Good Manufacturing 
Practices (cGMP). Monocytes are isolated from the PBMCs and are differentiated in vitro to 
generate dendritic cells (DCs), while the tumor biopsy specimen is used to isolate and amplify 
ribonucleic acid (RNA) that encodes autologous RCC antigens. AGS-003 is produced by 
electroporating the DCs with the tumor-derived amplified RNA, as well as with synthetically 
derived RNA that encodes the protein cluster of differentiated 40 ligand (CD40L). 
If there is a failure to isolate/amplify the RNA from the tumor biopsy specimen, the patient will 
be removed from the study and will proceed with standard of care treatment (i.e. partial or 
radical nephrectomy). 
Refer to the AGS-003 Dose Management Manual for detailed instructions. 
 Tumor Specimen for AGS-003  
6.1.1
Tumor specimens will be used for the manufacturing of AGS 003. Tumor tissue from a core 
needle biopsy will be obtained at the study site from each study participant at Screening, 
following standard institutional procedures. The tumor specimen containers will be shipped 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 18 of 46 
 
directly to Argos. Further instructions for tumor specimen collection, shipping, and handling are 
provided in the Argos Guideline for Core Biopsy Tumor Collection for RNA Preservation. 
Tumor specimens may be stored for up to 2 years after the last subject’s final study visit or per 
local regulatory requirements. 
 Leukapheresis 
6.1.2
The AGS-003 manufacturing process requires leukapheresis to collect autologous leukocytes. 
Study patients will be referred to the American Red Cross in Buffalo (3601 Union Rd, 
Cheektowaga, NY 14225). Even though leukapheresis occurs prior to administration of 
investigational product, RPCI will report to the FDA severe (Grade 3, CTCAE) or life-
threatening (Grade 4, CTCAE) events associated with the leukapheresis. 
The leukapheresis should not be performed less than 48 hours after the tumor biopsy procedure 
(Section 6.1.1). 
In most cases, only a single leukapheresis will be required to support product manufacture. 
However in some cases, cellular collection or manufacturing with the initial product is 
unsuccessful, and a second or third leukapheresis may be required. If additional leukapheresis 
(es) is required, standard treatment should still be initiated as clinically indicated. 
6.2 
Dosing and Administration 
AGS-003 will be manufactured and supplied in a single dose vial for each patient enrolled in the 
study, and will consist of autologous RNA-electroporated, mature DCs, 1.2 x 107 DCs per dose 
formulated in autologous plasma, 10% dimethyl sulfoxide (DMSO), and 10% Dextrose for 
Injection (50% w/v). 
AGS-003 study drug stocks are not stored long term at clinical sites. Instead, each individual 
dose will be shipped to RPCI 7 North Pharmacy according to a schedule mutually agreed upon 
by RPCI and Argos, under controlled conditions and in accordance will FDA approved 
guidelines for INDs. It will remain on 7-North unopened until administration. 
AGS-003 is for autologous use ONLY. Use is absolutely limited to the individual subject who is 
the autologous donor of the tumor, PBMCs and plasma used in the individual product lot 
identified by the SID (subject identification number). 
All injections will be administered by a protocol-trained health care provider. 
The target dose of AGS-003 (1.2 x 107 DCs) is delivered in three intradermal injections of 
0.2 mL each (0.6 mL total volume) at Injection Weeks #1, #2, and #3 (every 7 days, ± 2 days), 
followed by a partial or radical nephrectomy at the Nephrectomy Visit. Injections will be 
administered, with the location of injection sites documented by the Principal Investigator or 
protocol-trained medical personnel. 
 Intradermal Injection 
6.2.1
AGS-003 is administered via standard intradermal injection techniques: the entire dose 
(distributed in 3 syringes) is targeted to a single lymph node basin. The dose is delivered in three 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 19 of 46 
 
separate injection sites (approximately 5 cm from each other) in the axillary lymph node basin 
(or inguinal if needed), delivering 0.2 mL of study product at each site for 0.6 mL total, with 
subsequent doses alternating between the right and left sides. If axillary injections are not 
feasible (e.g., because of lymphedema or extensive Injection Site Reactions from preceding 
administrations), inguinal injections are allowed, alternating between the right and left groin. 
The treatment will be administered on an outpatient basis on 7-North of the RPCI main hospital. 
The Principal Investigator will demonstrate the injection technique to the nursing staff on 7-
North and, subsequent injections will be administered by the protocol-trained nursing staff. 
Following the injection, patients will remain on 7-North and will be monitored as outpatients for 
1 hour after AGS-003 injection. Monitoring will consist of vital sign measurements (temperature, 
heart rate, respiration rate, and BP) and local/systemic reactions to the injection. Patients will be 
monitored for side effects including inflammation and swelling in the draining lymph nodes. 
This monitoring will consist of clinical assessment of pain, tenderness, warmth and swelling. In 
the absence of adverse events, patients will be discharged 1 hour after injection from the 
outpatient clinic. 
6.3 
Dose Modifications 
Dose modification of AGS-003 is not permitted. AGS-003 should be administered per protocol 
regardless of changes in standard treatment. 
6.4 
General Concomitant Medication and Supportive Care 
 Permitted Medications 
6.4.1
Permitted medications include, but are not limited to, the following: 
• Standard vaccinations (e.g., influenza vaccine) 
• Intermittent use of antibiotics for sporadic infections as indicated 
• Bisphosphonates 
• Denosumab 
• Granulocyte colony-stimulating factor (G-CSF) 
• Erythropoietin stimulating agents 
• Transfusions of blood or blood products 
• Warfarin or low molecular weight heparin (LMWH) 
Corticosteroid use is permitted ONLY as defined below: 
• ≤ 10 mg/day prednisone or equivalent (e.g. ≤ 50 mg/day cortisone) and replacement 
steroids are permitted 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 20 of 46 
 
• Use of inhaled corticosteroids (e.g., for chronic obstructive pulmonary disease [COPD]) 
or ophthalmic steroids are permitted, but, if possible, should not be taken on the date of 
AGS-003 dosing 
• Intermittent topical use of corticosteroids (i.e., creams) to small areas of the skin, after 
consultation with the investigator (except that ISRs should not be treated with 
corticosteroids, as noted below) 
NOTE: Mild and moderate ISRs are expected and should resolve without sequelae. Injection site 
reactions should not be treated with any form of corticosteroids or antihistamines. If desired, 
non-steroidal anti-inflammatory topical ointments or drugs (NSAIDS) such as ibuprofen may be 
used to alleviate symptoms. 
 Prohibited Medications 
6.4.2
The following medications are prohibited: 
• Concomitant immunosuppressive or immunomodulatory agents 
• Use of cytokines (including products containing interferons or interleukins), or 
granulocyte macrophage colony stimulating factor (GM-CSF). NOTE: G-CSF is 
permitted (Section 6.4.1) 
• Chronic use of systemic corticosteroids, topical corticosteroids that are applied to large 
areas of the skin (exceeding the cumulative area of the palm of the subject’s hand), or any 
corticosteroids or antihistamines used on or near the injection sites, except as noted above 
under “Permitted Medications” 
 Drug Interactions 
6.4.3
There are no drugs that are known to directly interact with AGS-003. However, sorafenib, 
specified cytotoxic drugs, and chronic immunosuppressive therapies may negatively impact the 
mechanism of action of AGS-003, and are prohibited concomitant medications. 
6.5 
Treatment Discontinuation 
All patients who discontinue due to an AE must be followed until the event resolves or stabilizes. 
Appropriate medical care should be provided until signs and symptoms have abated, stabilized, 
or until abnormal laboratory findings have returned to acceptable or pre-study limits. The final 
status of the AE will be reported in the patient’s medical records and the appropriate eCRF. 
Reasons for treatment discontinuation should be classified as follows: 
• Death 
• Progressive disease 
• Treatment-related toxicity 
• Toxicity unrelated to treatment 
• Investigator judgment 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 21 of 46 
 
• The Investigator may withdraw a patient if, in his/her judgment, it is in the patient’s best 
interest to do so 
• Noncompliance 
• Patient voluntary withdrawal 
• A patient may withdraw from the study at any time, for any reason. If a patient 
discontinues treatment, an attempt should be made to obtain information regarding the 
reason for withdrawal. 
• Sponsor decision 
• Development of active autoimmune disease or other condition requiring chronic 
immunosuppressive therapy (such as rheumatoid arthritis, systemic lupus erythematous, 
multiple sclerosis, organ transplant recipient, etc.) 
• If, while on study, a patient shows any evidence of tumor progression independent of any 
SAE, study treatment will be discontinued, the patient’s RCC will be restaged, and the 
study investigator will discuss possible treatment options (including definitive therapy) 
with the patient. 
• If the study product is delayed > 2 weeks, the patient will discontinue the study and be 
allowed to proceed directly onto surgery and, the patient would be replaced in the study. 
7 
INVESTIGATIONAL PRODUCT 
7.1 
Active Substance and Source 
AGS-003 (IVT RNA-electroporated and cultured autologous mature DCs) is a personalized 
immunotherapeutic product whose autologous components are DCs (from a leukapheresis 
specimen) and RNA (from a tumor specimen). The tumor specimens and leukocytes are 
collected at the study site and shipped to Argos under controlled conditions in accordance with 
FDA-approved guidelines. AGS-003 is produced at Argos according to current Good 
Manufacturing Practice (cGMP). RNA that encodes autologous tumor antigens is isolated from 
the disease specimen and amplified. Monocytes are isolated from the leukapheresis collection 
and differentiated into DCs. The DCs are then co-electroporated with amplified tumor RNA as 
well as with RNA that encodes synthetically derived CD40L. 
Refer to the AGS-003 IB for additional manufacturing information. 
7.2 
Risks/Benefits of AGS-003 
Previous clinical studies have demonstrated that single-agent AGS-003 and its predecessor 
product MB-002 are safe and well-tolerated. Most drug-related AEs have been mild to moderate 
injection site reactions, with no reports of any drug-related AEs with Grade 3 or Grade 4 toxicity, 
and no drug-related serious adverse events (SAEs). No subjects in any studies of AGS-003 or 
MB-002 have developed autoimmune disease, and periodic assessments of autoimmunity 
markers in these studies have yielded no clinically significant findings. Of note, in all RCC 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 22 of 46 
 
studies each subject received AGS-003 manufactured from the subject’s renal tumor, yet no 
subjects developed autoimmune reactions against their remaining (healthy) kidney. 
According to the literature, serious reactions to DC products are rare. Theoretical risks include 
allergic reactions such as hives or rash, and development of a systemic autoimmune response. 
Other possible side effects include headache, nausea, and vomiting. Systemic AEs have included 
influenza-like symptoms (e.g., fever), diarrhea, and fatigue. 
Because AGS-003 is still in clinical development, it is unknown whether subjects who receive it 
will experience an improvement of their disease. 
7.3 
Packaging and Labeling 
AGS-003 is packaged and labeled at the Argos facility. Each lot is manufactured for a specific 
subject, therefore; the product labeling will include a unique, 8 digit subject-specific 
identification code (SID). Refer to AGS-003 Autologous Dendritic Cell Therapy Dose Manual 
for additional information. 
7.4 
Drug Shipment 
 AGS-003 CryoShipper System 
7.4.1
The AGS-003 dose will be transported in a liquid nitrogen CryoShipper system under controlled 
conditions at temperatures ≤ -150°C. The dry shipper system includes a "cryochamber" which is 
a small Dewar that has been charged with liquid nitrogen and that holds the dose in the vapor 
phase of this liquid nitrogen. The cryochamber in its shipping container must be stored 
UPRIGHT, in a secure location with access limited to study personnel only. 
Each CryoShipper will also have a label on the exterior with an expiration date for the 
CryoShipper. The CryoShipper label contains the following information: 
o Argos drug code (i.e. AGS-003) 
o Subject Identification (SID) (i.e. PST00000) 
Refer to AGS-003 Autologous Dendritic Cell Therapy Dose Manual for additional information. 
 Study Drug Shipments from Argos 
7.4.2
Individual doses of Study Drug for injection will be shipped separately (to RPCI 7 North 
Pharmacy) for each scheduled administration. The site coordinator and Argos will coordinate to 
schedule shipment of each dose. 
As soon as the CryoShipper is received, the designated staff must verify that the tamper-proof 
tape is intact and that the liquid nitrogen shipping container (CryoShipper) is not damaged. 
Remove the tamper proof tape, undo the latches and open the lid, then retrieve the shipping 
documents. 
Refer to AGS-003 Autologous Dendritic Cell Therapy Dose Manual for additional information. 
 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 23 of 46 
 
7.5 
Dose Preparation and Administration 
A detailed description and outline is provided in the AGS-003 Autologous Dendritic Cell 
Therapy Dose Manual. 
AGS-003 is a biological product which contains live cellular material. AGS-003 is prepared 
under aseptic conditions and is formulated for administration as supplied, using aseptic injection 
techniques. 
Each dose of AGS-003 will be provided as a single-dose vial for injection. The product is 
supplied frozen and must be thawed immediately prior to use. 
Each dose of AGS-003 (0.6 mL total volume) will be delivered in three intradermal (i.d.) 
injections of 0.2 mL each, using the intradermal syringes provided with the dose shipment. Dose 
modifications are not permitted. 
All injections should be administered within 30 minutes of vial removal from the cryogenic 
chamber (liquid nitrogen Dewar) to maximize cell viability. If more than 30 minutes has elapsed 
from the time the cryogenic chamber has been opened and single dose vial removed, administer 
the dose as soon as possible and notify Argos immediately. 
Axillary or inguinal sites must be used for injections, with the entire dose (distributed in 
3 syringes) targeted to a single lymph node basin. Axillary injection sites are preferred. Right 
and left axillary injections must be made in the lateral aspect of the chest wall as near to the 
shoulder as practical. 
If axillary injections are not feasible (e.g. because of lymphedema or extensive Injection Site 
Reactions from preceding administrations), inguinal injections are allowed, alternating between 
the right and left groin. Inguinal injections must be made to the anteromedial aspect of the limb 
as close to the inner groin as possible. 
All three injections comprising the single AGS-003 dose should be targeted to a single lymph 
node area. AGS-003 is administered to a lymph node basin to deliver dendritic cells as close to 
the lymph areas as possible. However, do not attempt to directly inject the actual lymph nodes. 
In final preparation for dose administration, TWO staff personnel must compare the subject 
identification (SID) on the syringe labels to the SID listed in the subject's medical chart, and 
verify that the correct medical chart is present for the subject. Document this final dose 
verification in the Investigational Product Accountability Log. 
Administer the product via standard intradermal injection techniques; the entire dose (distributed 
in 3 syringes) is targeted to a single lymph node basin. The dose is delivered in three separate 
injection sites in the axillary lymph node basin (or inguinal if needed), delivering 0.2 mL of 
study product at each site for 0.6 mL total. The 3 injection sites must be approximately 5 cm 
from each other, and subsequent doses will alternate between the right and left sides. Injections 
must be administered by a protocol-trained health care provider. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 24 of 46 
 
 Injection Site Reactions 
7.5.1
Mild and moderate injection site reactions are expected and should resolve without sequelae. 
Injection site reactions should not be treated with any form of corticosteroids or antihistamines. 
If desired, non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may be used to 
alleviate symptoms. Should a more serious or systemic immune reaction (e.g., upper extremity, 
facial flushing) occur, standard treatment with antihistamines and other medications would be 
permitted to manage the reaction. 
7.6 
Handling and Disposal 
AGS-003 is a biological product which contains live cellular material. AGS-003 is prepared 
under aseptic conditions and is ready for administration as supplied, using aseptic injection 
techniques. Since each dose of AGS-003 has been manufactured for use by a specific subject, 
verification procedures must be followed. The AGS-003 shipper must remain unopened at the 
clinical trial site until the subject is present and, both the subject and site staff are ready for dose 
administration. 
The Investigator or designee will be responsible for dispensing and accounting for all 
investigational drug provided by Argos, exercising accepted medical and pharmaceutical 
practices. Study drugs must be handled as infectious agents and appropriate precautions taken 
per the institution’s environmentally safe handling procedures. All investigational drugs will be 
dispensed in accordance with the Investigator’s prescription or written order. 
Additionally, for each study subject/dose, the site is instructed to record the time of vial removal 
from the shipper, the time of dose injection, the volume of dose administered, whether leak-back 
was observed from any injection sites, and a study drug disposition log that records the final 
disposition of each dose. 
After dosing, any unused product must be destroyed. The clean-up and disposal of spilled, 
wasted, or unused medication and of used syringes must be documented appropriately in 
accordance with applicable federal regulations, Good Clinical Practice (GCP) procedures, and 
the procedures for handling biohazardous substances. Discard the empty vial and used syringes 
as you would any biohazardous material per institutional policies. Partially used vials of the 
study drug will not be re-used for other patients. 
8 
STUDY PROCEDURES 
8.1 
Patient Registration 
Eligibility of each patient will be established prior to enrollment. 
Informed consent must be completed prior to receiving any study-related procedures. 
8.2 
Screening 
The following evaluations will be performed within 4 weeks prior to tumor biopsy: 
• Medical history (including all prior anti-tumoral therapy related to RCC) 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 25 of 46 
 
• Physical examination, including vital signs (i.e., temperature, heart rate, respiratory rate, 
blood pressure), body weight, and height 
• Hematology: 
o (i.e., complete blood count (CBC) with automated differentials): WBC, RBC, HGB, 
HCT, platelet, MCV, MCH, MCHC, %neutrophils, absolute neutrophils, 
,%monocytes, absolute monocytes, %eosinophils, absolute eosinophils, %basophils, 
absolute basophils, %lymphocyte total, absolute lymphocyte total, platelet 
confirmation (as clinically indicated), and differential confirmation (as clinically 
indicated). 
• Chemistry: 
o Complete Metabolic Panel (i.e., CMP: chloride, CO2, potassium, sodium, BUN, 
glucose, calcium, creatinine, total protein, albumin, bilirubin total, alkaline 
phosphatase, AST, ALT, osmol (calc), anion gap, B/C ratio, A/G ratio) along with 
gamma-glutamyl transferase (GGT), lactose dehydrogenase (LDH), phosphorus, 
magnesium, uric acid, thyroid stimulating hormone (TSH), c-reactive protein (CRP), 
and corrected calcium.  
• Autoimmunity Assessment: 
o Rheumatoid factor (RF) 
o Anti-thyroglobulin antibody (TG) 
o Anti-double stranded DNA antibody (dsDNA antibody) 
o Anti-nuclear antibody (ANA) 
• ECOG Performance Status (see Appendix A) 
• Tumor assessment, including CT scan of the chest, abdomen, and pelvis 
• Concomitant Medications List any ongoing medications with an onset within 1 week of 
tumor biopsy 
• Pregnancy test (urine) in females of childbearing potential 
Tumor biopsy for AGS-003 in accordance with Argos requirements will also be performed at 
Screening. 
8.3 
Leukapheresis Visit (must occur within 3 weeks after biopsy) 
Leukapheresis: Leukapheresis for AGS-003 manufacturing should be performed 3 weeks after 
tumor biopsy. Scheduling of leukaphapheresis will be determined by American Red Cross 
availability. Patient may need second leukapheresis based on success of first one. All efforts will 
be made to ensure that second leukapheresis will be within the 3 week timeframe but will not be 
considered a protocol deviation if it falls out of this window. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 26 of 46 
 
8.4 
AGS-003 Treatment Phase 
The manufacturing of the vaccine can take 6-12 weeks. Due to the unexpected nature of the 
timeline of manufacturing, once the vaccine has been successfully created and ready to be 
shipped to RPCI, the study coordinator will work with Argos and all site staff to ensure that 
scheduling for proper administration and safety testing is performed. Injections should be given 7 
days apart. Shipments are sent from Argos one dose at a time. Shipment delays and other 
unexpected events do occur therefore a dosing window of +/- 2 days will be allowed for each 
dose.  
 Injection Week #1 
8.4.1
• Vital Signs, weight 
• ECOG Performance Status 
• Concomitant medications 
• Adverse events 
• Hematology, Chemistry, Autoimmune and Immunologic assessment prior to dosing 
• Administer AGS-003, 1st dose 
 Injection Week #2 
8.4.2
• Vital Signs, weight 
• ECOG Performance Status 
• Concomitant medications 
• Adverse events 
• Administer AGS-003 2nd dose 
 Injection Week #3 
8.4.3
• Vital Signs, weight 
• ECOG Performance Status 
• Concomitant medications 
• Adverse events 
• Hematology, Chemistry, and Autoimmune assessment prior to dosing 
• Administer AGS-003 3rd dose 
 Nephrectomy Visit 
8.4.4
Partial or radical nephrectomy will be performed at this visit.  

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 27 of 46 
 
The following assessments are also performed at this time. If there is a pre-operative visit, the 
assessments may be performed as part of that visit instead. Otherwise, assessments are to be 
performed on day of scheduled nephrectomy, prior to surgery. 
• Concomitant medications 
• Adverse events 
• Blood draw for Immunologic assessment 
• Blood draw for Hematology, Chemistry and Autoimmunity assessment 
• Tissue sample from nephrectomy. 
8.5 
End of Study Visit/ Follow-Up 
The end of study visit is conducted approximately one month following nephrectomy, or any 
time the subject discontinues the study. The following assessments will be performed: 
• Physical examination including vital signs and weight 
• Hematology: Complete Blood Count with automated differential (CBC/DIFF) 
• Chemistry: Complete Metabolic Panel (P22 COMP) 
• Blood draw for Immunological analysis 
• Blood draw for Autoimmunity assessment 
• Pregnancy test (urine) in females of childbearing potential 
• ECOG Performance Status (see Appendix A) 
• Concomitant medication 
• Adverse events (surgical AEs only if clinically significant) 
8.6 
Schedule of Procedures and Observations 
The schedule of procedures and observations for this study is summarized in Table 1. 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 28 of 46 
 
Table 1. 
Schedule of Procedures and Observations 
 
Screening1 
Leukapheresis 
Visit 
Injection 
Week #1 
Injection 
Week #2 
Injection 
Week #3 
Nephrectomy 
Visit 
End of Study/ 
Follow -Up3 
Medical History 
X 
 
 
 
 
 
 
Physical Examination 
X 
 
 
 
 
 
X 
Vital Signs & ECOG13 
X 
 
X 
X 
X 
 
X 
Prior/Concomitant Medications  
X4 
 
X 
X 
X 
X 
X 
Adverse Events 
 
 
X 
X 
X 
X 
X 
Chemistry5 
X 
 
X 
 
X 
X 
X 
Hematology 6 
X 
 
X 
 
X 
X 
X 
Autoimmunity Assessment7 
X 
 
X 
 
X 
X 
X 
Pregnancy Test (urine)8 
X 
 
 
 
 
 
X 
Tumor Assessment 9 
X 
 
 
 
 
 
 
Tumor Biopsy for AGS-003 
X 
 
 
 
 
 
 
Leukapheresis for AGS-00310 
 
X 
 
 
 
 
 
AGS-003 Dose11 
 
 
1st 
2nd 
3rd 
 
 
Blood Sampling for 
Immunologic Assessment 12 
 
 
X 
 
 
X 
X 
Nephrectomy 
 
 
 
 
 
X 
 
Tissue  from Nephrectomy 
 
 
 
 
 
X 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 29 of 46 
 
Notes for Table 1 
1. 
Performed within 4 weeks prior to Leukapheresis Visit. 
2. 
If there is a pre-operative visit, Nephrectomy Visit assessments may be performed as part 
of that visit instead. Otherwise, assessments, including immunologic, are to be performed 
on day of nephrectomy prior to surgery. 
3. 
Performed at post op visit following nephrectomy, or if subject discontinues or is 
withdrawn from the study. 
4. 
Medications ongoing within 1 week prior to tumor biopsy. 
5. 
Chemistry: Complete Metabolic Panel (i.e., CMP: chloride, CO2, potassium, sodium, 
BUN, glucose, calcium, creatinine, total protein, albumin, bilirubin total, alkaline 
phosphatase, AST, ALT, osmol (calc), anion gap, B/C ratio, A/G ratio) along with 
gamma-glutamyl transferase (GGT), lactose dehydrogenase (LDH), phosphorus, 
magnesium, uric acid, thyroid stimulating hormone (TSH), c-reactive protein (CRP), and 
corrected calcium. NOTE: On Injection Weeks #1 and #3 assessments should be taken 
prior to dosing. At Nephrectomy Visit the assessments can be taken either at a pre-
operative visit or on the day of nephrectomy prior to surgery. 
6. 
Hematology:[(i.e., complete blood count (CBC) with automated differentials): WBC, 
RBC, HGB, HCT, platelet, MCV, MCH, MCHC, %neutrophils, absolute neutrophils, 
%monocytes, absolute monocytes, % eosinophils, absolute eosinophils, %basophils, 
absolute basophils,), %lymphocyte total, absolute lymphocyte total, platelet confirmation 
as clinically indicated. Grade 4 neutropenia should be monitored according to 
institutional guidelines. NOTE: On Injection Weeks #1 and #3 assessments should be 
taken prior to dosing. At Nephrectomy Visit the assessments can be taken either at a pre-
operative visit or on the day of nephrectomy prior to surgery. 
7. 
On Injection Weeks #1 and #3 assessment should be taken prior to dosing. At 
Nephrectomy Visit the assessment can be taken either at a pre-operative visit or on the 
day of nephrectomy prior to surgery: Rheumatoid Factor (RF), Anti-thyroglobulin (TG), 
Anti-double stranded DNA antibody (dsDNA antibody), Anti-nuclear antibody (ANA). 
8. 
Only applicable to females of child-bearing potential. 
9. 
To include CT scan of the chest, abdomen, and pelvis. 
10. American Red Cross (3601 Union Rd, Cheektowaga, NY 14225) in accordance with 
Argos requirements. Should not be performed less than 48 hours after tumor biopsy 
procedure. 
11. Perform any required Chemistry, Hematology, Autoimmune and Immunologic 
assessment blood draws before AGS-003 dosing. Observe possible Injection Site 
Reactions for 1 hour post injection. Assess Vital signs (temperature, heart rate, 
respiration rate, BP). The target dose of AGS-003 (1.2 x 107 DCs) is delivered in three 
intradermal injections of 0.2 mL each (0.6 mL total volume) at Injection Weeks #1, #2, 
and #3 (every 7 days, ± 2 days). 
12. For Argos Immune Monitoring: Six, 10 mL green-top heparinized collection tubes, (tubes 
provided in kit). Refer to Section 9.1.1. For Correlative Studies Samples: Four, 10 mL 
green-top heparinized collection tubes: Refer to 9.1.2. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 30 of 46 
 
13. Screening vital signs: temperature, heart rate, respiration rate, BP, height and weight. 
Dose days and End of Study: all but height. 
9 
BIOLOGICAL SPECIMEN MANAGEMENT 
9.1 
Blood Sample Collection and Processing for Immunologic Analysis 
 Samples for Argos Immune Monitoring 
9.1.1
Samples for immunologic analysis (six 10 mL green-top heparinized collection tubes) will be 
collected in the Phlebotomy Laboratory prior to the initial AGS-003 dose, after the 3rd dose, and 
at the final study visit. Samples will be sent to Laboratory Medicine for same day shipment to 
Argos Therapeutics, Inc. (Refer to Argos Immune Monitoring Sampling Kit Instructions and 
Immune Monitoring Sample Worksheet.) Immune monitoring samples are sent to the following 
address on the Day of Collection (Monday through Thursday): 
Argos Therapeutics, Inc. 
4233 Technology Drive 
Durham, NC 27704-2173 
immunomonitoring@argostherapeutics.com 
 Samples for Correlative Studies 
9.1.2
Samples for the study correlative analyses (four 10 mL green-top heparinized collection tubes) 
will be collected in the Phlebotomy Laboratory at the same times as those for Immune 
Monitoring described above (prior to the initial AGS-003 dose, after the 3rd dose, and at the final 
study visit) and sent to the Hematological Procurement Facility. 
Plasma and PBMC will be separated from the total blood within 30 minutes following the 
extraction. The screw cap polypropylene cryogenic tube will be labeled with the patient’s MR 
number, patient’s initials, patient’s study number, clinical study number, protocol time point, 
dose, and protocol day. The label for each patient’s sample will be supplied by RPCI. The 
samples will immediately be frozen at -70ºC or below until analyzed and the PBMCs will be 
stored in liquid nitrogen. The samples will be stored in the Hematologic Procurement Facility 
and batch-shipped to Dr. Schwaab’s Laboratory for analysis. 
Samples will be analyzed in Dr. Schwaab’s laboratory: 
Buffalo Life Sciences Complex (BLSC) 
Center for Genetics and Pharmacology (CGP) 
Laboratory location: L5-141 
Lab phone: 716-845-7180 
Lab contacts: 
Mohammad Habiby Kermany, MD PhD-Lab Manager 
Jason Muhitch, PhD, Assistant Professor, office number: 716-845-4930 
Dr. Muhitch’s cell phone number: 716-983-7134 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 31 of 46 
 
Dr. Schwaab’s office number: 716-845-5770 
Dr. Schwaab’s cell phone number: 716-544-0416 
Note: All investigator or analyzing research laboratories housing research samples need to 
maintain current Temperature Logs and study-specific Sample Tracking and Shipping Logs. 
The Principal Investigator/Laboratory Manager must ensure that the stated lab(s) have a process 
in place to document the receipt/processing/storage/shipping of study-related samples/specimens. 
This is required for both observational and interventional clinical studies collecting clinical 
samples. 
Refer to Section 13 for correlative data analysis. 
9.2 
Leukapheresis 
Leukapheresis for AGS-003 manufacturing will be performed at the American Red Cross 
according to the Argos Leukapheresis Manual and sent directly to Argos on the day of collection. 
9.3 
Nephrectomy 
Fresh tissue will be obtained from the surgical specimen to evaluate the effect of AGS-003 
treatment. Samples to be taken are primarily tumor tissue, but may also include normal kidney, 
adrenal gland, lymph nodes, and /or surrounding tissues as included in the resection. The 
minimum amount needed is 1g and optimum is 10 gramsbut additional amounts will be accepted 
if not required for other institutional research. 
The fresh tissue will be sent to Dr. Schwaab’s laboratory for processing: 
Buffalo Life Sciences Complex (BLSC) 
Center for Genetics and Pharmacology (CGP) 
Laboratory location: L5-141 
Lab phone: 716-845-7180 
Lab contacts: 
Mohammad Habiby Kermany, MD PhD-Lab Manager 
Jason Muhitch, PhD, Assistant Professor, office number: 716-845-4930 
Dr. Muhitch’s cell phone number: 716-983-7134 
Dr. Schwaab office number: 716-845-5770 
Dr. Schwaab cell phone number: 716-544-0416 
For historical comparison, the RCC TMA in existence will be used. 
Note: All investigator or analyzing research laboratories housing research samples need to 
maintain current Temperature Logs and study-specific Sample Tracking and Shipping Logs. 
The Principal Investigator/Laboratory Manager must ensure that the stated lab(s) have a process 
in place to document the receipt/processing/storage/shipping of study-related samples/specimens. 
This is required for both observational and interventional clinical studies collecting clinical 
samples. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 32 of 46 
 
Nephrectomy tissue will also be sent to Argos. Kit for tissue will be provided for each patient by 
Argos. Sample will be sent to CRS Lab Path Team for processing and shipping. Please see Argos 
Tumor Worksheet 
 
Tumor Specimen Collection Guidelines for Argos  
 
1 The tumor specimen biopsied must represent viable, non-necrotic tissue that is at least 70% 
tumor  
 
2 Prepare tumor specimen by completing four (4) biopsy passes for each vial of RNA 
preservative using 16 gauge or 18 gauge biopsy needles.  
NOTE: DO NOT place the specimen in formalin or any other fixative.  
NOTE: DO NOT use absorbent material while preparing the tumor specimen.  
 
3 Place the tumor specimen into the RNA preservative vial(s), cap, and gently swirl to separate 
specimen pieces and adequately immerse specimen pieces in preservative.  
NOTE: Only use RNA preservative vials provided with this kit.  
 
4 The tumor specimen should be shipped at room temperature the same day as collection. If the 
shipment cannot go out the same day as collection, the sealed kit with the tumor specimen in it 
must be stored in a 2-8° C refrigerator until ready for shipment. 
9.4 
Pathology 
 Pre-Treatment Formalin-Fixed Paraffin Embedded (FPPE) Biopsy Samples 
9.4.1
The following sections of tissue from the most recent (Screening) renal cell tissue biopsy 
(neoplastic) that exists in the Paraffin Archive in the Department of Pathology will be collected: 
• Ten (10) unstained sections cut at 5 microns on plus glass slides. 
The study coordinator or designee will be responsible for entering the order into the EMR using 
the standard format for all clinical trial pathology requirements. 
 Post-Treatment Resection Formalin-Fixed Paraffin Embedded (FPPE) Samples 
9.4.2
The following sections of tissue from the end of treatment nephrectomy (primarily tumor tissue, 
but may also include normal kidney, adrenal gland, lymph nodes, and /or surrounding tissues) 
that exists in the Paraffin Archive in the Department of Pathology will be collected: 
• Ten (10) unstained sections cut at 5 microns on plus glass slides. 
The study coordinator or designee will be responsible for entering the order into the EMR using 
the standard format for all clinical trial pathology requirements. 
Once the samples have been processed by the Pathology Department at RPCI, they will be sent 
to Dr. Schwaab’s laboratory: 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 33 of 46 
 
Buffalo Life Science Complex (BLSC) 
Center for Genetics and Pharmacology (CGP) 
Laboratory location: L5-141 
Lab phone: 716.845.7180 
Lab Contacts: 
Mohammed Habiby Kermany 
Jason Muhitch, PhD, Assistant Professor, office number: 716-845-4930 
Dr. Muhitch’s cell phone number: 716-983-7134 
Dr. Schwaab office number: 716.845.5770 
Dr. Schwaab cell phone number: 716.544.0416 
Slides will be shipped by the investigator to Adaptive Biotechnologies, Seattle Washington, for 
analysis.  
Note: All investigator or analyzing research laboratories housing research samples need to 
maintain current Temperature Logs and study-specific Sample Tracking and Shipping Logs. 
The Principal Investigator/Laboratory Manager must ensure that the stated lab(s) have a process 
in place to document the receipt/processing/storage/shipping of study-related samples/specimens. 
This is required for both observational and interventional clinical studies collecting clinical 
samples. 
10 SAFETY EVALUATION 
Safety will be assessed through physical examinations, medical history, clinical laboratory tests, 
vital sign assessments, and evaluation of adverse events (AEs). Assessments will include grading 
of the frequency and severity of AEs associated with the treatment, including but not limited to 
clinical laboratory values, autoimmunity evaluations, and evaluations of injection site reactions 
(ISRs). 
10.1 Medical History 
During study Pre-treatment, a complete medical history will be obtained that includes medical 
and oncologic history, demographics (date of birth, sex, race, ethnicity), history of other disease 
process (active or resolved), medication history, and concomitant illness. The medical history 
must be documented in the subject’s chart. 
10.2 Physical Examination 
A physical exam that includes a complete review of major body systems and vital signs will be 
performed by the investigator or designee during Pre-treatment and at the End of 
Study/Follow-up visit. Vital sign measurements to be obtained include systolic and diastolic 
blood pressure, heart rate, weight, height (at Pre-treatment only), body temperature, and 
respiratory rate. 
10.3 Autoimmunity Assessments 
Autoimmune laboratory parameters (i.e. RF, TG, dsDNA antibody, ANA) will be followed for 
shifts from Screening assessment on Injection Week #1 (prior to dosing), Injection Week #3 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 34 of 46 
 
(prior to dosing), Nephrectomy Visit (either at pre-operative visit or on day of nephrectomy prior 
to surgery), and at End of Study/ Follow-Up visit. Autoimmunity results from the laboratory will 
be assessed by the investigator for clinical significance. Abnormal laboratory parameters, even as 
assessed as clinically non-significant, will require closer examination for other indications of 
clinically manifested autoimmune disease. Abnormal laboratory parameters will be followed by 
clinical evaluations and repeated laboratory assessments as indicated by the investigator. 
Clinically confirmed occurrences of autoimmunity will be reported expeditiously to Argos 
Therapeutics. Any subject who develops autoimmune disease will be withdrawn from the study 
(refer to Section 6.5). 
10.4 Injection Site Reaction and Post-Dose Vital Signs Evaluation 
Injection sites will be examined for reactions and vital signs assessed 1 hour following AGS-003 
administration, while the subject remains in the clinic. Subjects will also be instructed to conduct 
self-examinations of the injection sites and to contact study staff if a reaction occurs or worsens 
after a study visit. Mild and moderate ISRs are expected and should resolve without sequelae. 
Injection site reactions should not be treated with any form of corticosteroids or antihistamines. 
If desired, non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen may be used to 
alleviate symptoms. 
10.5 Adverse Events 
 Definition 
10.5.1
An adverse event or adverse experience (AE) is any untoward medical occurrence associated 
with the use of a drug in humans, whether or not considered drug related. Therefore, an AE can 
be ANY unfavorable and unintended sign (including an abnormal laboratory finding, if clinically 
significant), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not considered related to the medicinal (investigational) 
product (attribution of ‘unrelated’, ‘unlikely’, ‘probable’, or ‘definite’). 
An AE is considered “unexpected” if it is not listed in the investigator brochure or is not listed at 
the specificity or severity that has been observed; or if an investigator brochure is not required or 
available, is not consistent with the risk information described in the general investigational plan 
in other study-related documents. 
 Diagnosis Versus Signs and Symptoms 
10.5.2
If known, a diagnosis should be recorded on the CRF rather than individual signs and symptoms 
(e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases). However, if a constellation of signs and/or symptoms cannot be clinically 
characterized as a single diagnosis or syndrome at the time of reporting, each individual event 
should be recorded as an AE or SAE on the CRF. If a diagnosis is subsequently established, it 
should be reported as follow-up information. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 35 of 46 
 
 Adverse Events Occurring Secondary to Other Events 
10.5.3
In general, AEs occurring secondary to other events (e.g., cascade events or clinical sequelae) 
should be identified by their primary cause. For example, if severe diarrhea is known to have 
resulted in dehydration, it is sufficient to record only diarrhea as an AE or SAE on the CRF. 
However, clinically significant AEs occurring secondary to an initiating event that are separated 
in time should be recorded as independent events on the CRF. For example, if a severe 
gastrointestinal hemorrhage leads to renal failure, both events should be recorded separately on 
the CRF. 
 Abnormal Laboratory Values 
10.5.4
Only clinically significant laboratory abnormalities that require active management will be 
recorded as AEs or SAEs on the CRF (e.g., discontinuation of study treatment, more frequent 
follow-up assessments, further diagnostic investigation, etc.). 
If the clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 x the upper limit of normal associated with 
cholecystitis), only the diagnosis (e.g., cholecystitis) needs to be recorded on the Adverse Event 
CRF. 
If the clinically significant laboratory abnormality is not a sign of a disease or syndrome, the 
abnormality itself should be recorded as an AE or SAE on the CRF. If the laboratory abnormality 
can be characterized by a precise clinical term, the clinical term should be recorded as the AE or 
SAE. For example, an elevated serum potassium level of 7 mEq/L should be recorded as 
“hyperkalemia”. 
Observations of the same clinically significant laboratory abnormality from visit to visit should 
not be repeatedly recorded as AEs or SAEs on the CRF, unless their severity, seriousness, or 
etiology changes. 
 Preexisting Medical Conditions (Baseline Conditions) 
10.5.5
A preexisting medical condition should be recorded as an AE or SAE only if the frequency, 
severity, or character of the condition worsens during the study. When recording such events on 
an Adverse Event CRF, it is important to convey the concept that the preexisting condition has 
changed by including applicable descriptors (e.g., “more frequent headaches”). 
10.6 Grading and Relationship to Drug 
The descriptions and grading scales found in the CTEP Version 4 of the NCI Common 
Terminology Criteria for Adverse Events (CTCAE) will be utilized for AE reporting. The 
location of the CTCAE CTEP V.4 is: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
AEs not covered by specific terminology listed should be reported with common medical 
terminology and documented according to the grading scales provided in the CTCAE Version 4. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 36 of 46 
 
The relationship of event to study drug will be documented by the Investigator as follows: 
• Unrelated: The event is clearly related to other factors such as the patient’s clinical state, 
other therapeutic interventions or concomitant drugs administered to the patient. 
• Unlikely: The event is doubtfully related to the investigational agent. The event was most 
likely related to other factors such as the patient’s clinical state, other therapeutic 
interventions, or concomitant drugs. 
• Possible: The event follows a reasonable temporal sequence from the time of drug 
administration, but could have been produced by other factors such as the patient’s 
clinical state, other therapeutic interventions or concomitant drugs. 
• Probable: The event follows a reasonable temporal sequence from the time of drug 
administration, and follows a known response pattern to the study drug. The event cannot 
be reasonably explained by other factors such as the patient’s clinical state, therapeutic 
interventions or concomitant drugs. 
• Definite: The event follows a reasonable temporal sequence from the time of drug 
administration, follows a known response pattern to the study drug, cannot be reasonably 
explained by other factors such as the patient’s condition, therapeutic interventions or 
concomitant drugs; AND occurs immediately following study drug administration, 
improves upon stopping the drug, or reappears on re-exposure. 
10.7 Reporting Adverse Events 
Table 2. 
Guidelines for Routine Adverse Event Reporting for Pilot Studies 
(Regardless of Expectedness) 
Attribution 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Unrelated 
 
 
X 
X 
Unlikely 
 
 
X 
X 
Possible 
X 
X 
X 
X 
Probable 
X 
X 
X 
X 
Definite 
X 
X 
X 
X 
All routine AEs occurring between the start of intervention until 30 days after the last 
intervention or until the event has resolved, the study patient is lost to follow-up, the start of a 
new treatment, or until the study investigator assesses the event(s) as stable or reversible, will be 
reported. New information will be reported when it is received. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 37 of 46 
 
10.8 Serious Adverse Events 
 Definition 
10.8.1
A serious adverse event (SAE) is any adverse event (experience) that in the opinion of either the 
investigator or sponsor results in ANY of the following: 
• Death 
• A life-threatening adverse event (experience). Any AE that places a patient or patient, in 
the view of the Investigator or sponsor, at immediate risk of death from the reaction as it 
occurred. It does NOT include an AE that, had it occurred in a more severe form, might 
have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization (for > 24 hours). 
Admission for scheduled nephrectomy will not be considered an SAE. 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly or birth defect 
• Important Medical Event (IME) that, based upon medical judgment, may jeopardize the 
patient and may require medical or surgical intervention to prevent one of the outcomes 
listed above 
 Reporting Serious Adverse Events 
10.8.2
All new SAEs occurring from the date the patient signs the study consent until 30 days after the 
last intervention or a new treatment is started, whichever comes first, will be reported. The RPCI 
SAE Source Form is to be completed with all available information, including a brief narrative 
describing the SAE and any other relevant information.   
SAE’s occurring after the 30 day follow-up period that the investigator determines to be 
possibly, probably or definitely related to the study intervention, should be reported. 
SAE’s identified as an Unanticipated Problem by the Investigator must be reported. Please refer 
to Section 10.9.2 for details on reporting Unanticipated Problems. 
 Investigator Reporting: Notifying the AGS-003 manufacturer 
10.8.3
SAEs that meet requirements for expedited reporting (probably or definitely related to AGS-003) 
and are inconsistent with the safety profile in the current AGS-003 IB must be rapidly reported to 
Argos. 
Argos Therapeutics, Inc. 
4233 Technology Drive 
Durham, NC 27704-2173 
Ph. 919-287-6300 
Fax 919-287-6301 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 38 of 46 
 
 Follow-Up for Serious Adverse Events 
10.8.4
All related SAEs should be followed to their resolution, the study patient is lost to follow-up, the 
start of a new treatment, or until the study investigator assesses the event(s) as stable or 
irreversible. New information will be reported when it is received. 
10.9 Unanticipated Problems 
 Definition 
10.9.1
An Unanticipated Problem (UP) is any incident, experience, or outcome that meets all of the 
following criteria: 
• Unexpected (in terms of nature, severity, or frequency) given: 
o The research procedures that are described in the study-related documents, including 
study deviations, as well as issues related to compromise of patient privacy or 
confidentiality of data. 
o The characteristics of the patient population being studied. 
• Related or possibly related to participation in the research (possibly related means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research). 
• Suggests that the research places patients or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized and if in relation to an AE is also deemed serious per Section 10.8. 
 Reporting Unanticipated Problems 
10.9.2
Unanticipated problem reporting will begin at the time of participant consent. The Unanticipated 
Problem Form will be submitted to CRS Compliance Office within 1 business day of becoming 
aware of the Unanticipated Problem. After review, CRS Compliance will submit the UP to the 
IRB. 
When becoming aware of new information about the Unanticipated Problem, submit this updated 
information to CRS Compliance with an updated Unanticipated Problem Form. The site 
Investigator or designated research personnel will report all unanticipated problems, whether 
related or unrelated to the investigational agent(s) to the IRB in accordance with their local 
institutional guidelines. 
10.10 FDA Reporting 
When RPCI is the IND holder the following describes the FDA reporting requirements by 
timeline for AEs and new safety findings that meet the criteria outlined below: 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 39 of 46 
 
Within 7 Calendar Days 
Any adverse event that meets ALL the following criteria: 
• Related or possibly related to the use of the study drug; 
• Unexpected; and 
• Fatal or life-threatening. 
Within 15 Calendar Days 
Any adverse event that meets ALL the following criteria: 
• Related or possibly related to the use of the study drug; 
• Unexpected; and 
• Serious but not fatal or life-threatening. 
Or, meets ANY of the following criteria: 
• A previous adverse event that is not initially deemed reportable but is later found to fit 
the criteria for reporting (report within 15 days from when event was deemed reportable). 
• Any findings from other studies, including epidemiological studies, pooled analysis of 
multiple studies, or other clinical studies conducted with the study drug that suggest a 
significant risk in humans exposed to the drug. 
• Any findings from animal or in vitro testing that suggest a significant risk for human 
patients including reports of mutagenicity, teratogenicity, or carcinogenicity or reports of 
significant organ toxicity at or near the expected human exposure. 
• Any clinically important increase in the rate of occurrence of a serious, related or 
possibly related adverse event over that listed in the protocol or investigator brochure. 
Sponsors are also required to identify in IND safety reports, all previous reports concerning 
similar adverse events and to analyze the significance of the current event in the light of the 
previous reports. 
Reporting Process 
The principal investigator or designee will complete and submit a FDA Form 3500A MedWatch 
for any event that meets the above criteria. Forms will be submitted to the CRS Compliance 
Office via email to CRSCompliance@RoswellPark.org. 
10.11 Gene Therapy Study Reporting of Serious Adverse Events 
Studies that involve Gene Therapy will report SAEs as described above and will be reported to 
the Office of Biotechnology Activities (OBA) / NIH. 
Any SAE that is fatal or life-threatening, that is unexpected, and associated with the use of the 
gene transfer product must be reported to the FDA and NIH OBA as soon as possible, but not 
later than 7 calendar days after the Sponsor’s initial receipt of the information. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 40 of 46 
 
SAEs that are unexpected and associated with the use of the gene transfer product, but are not 
fatal or life-threatening, must be reported to the FDA and NIH OBA as soon as possible, but not 
later than 15 calendar days after the sponsor’s initial receipt of the information. 
If, after further evaluation, an adverse event initially considered not to be associated with the use 
of the gene transfer product is subsequently determined to be associated, then the event must be 
reported to the NIH OBA within 15 days of the determination. 
Any follow-up information relevant to a SAE must be reported within 15 calendar days of the 
Sponsor’s receipt of the information. If a SAE occurs after the end of a clinical trial and is 
determined to be associated with the use of the gene transfer product, that event shall be reported 
to the NIH OBA within 15 calendar days of the determination. 
The Principal Investigator or delegated research staff will submit a report to the CRS 
Compliance Office via email: CRS Compliance for all gene therapy SAEs. The Compliance 
office will forward the information to ORSP. 
Completed reports may be sent via U.S. mail, courier service, e-mail, or facsimile to: 
NIH Office of Biotechnology Activities 
6705 Rockledge Drive, Suite 750 
Bethesda, Maryland 20892-7985 
(For all non-USPS deliveries use Zip Code 20817) 
Telephone: 301-496-9838 
Fax: 301-496-9839 
E-mail address for Reporting Adverse Events: GeMCRIS@od.nih.gov 
General E-mail: oba@od.nih.gov 
Website: http://oba.od.nih.gov/oba/index.html 
Additional information for reporting adverse events, including a report template, can be found at: 
http://oba.od.nih.gov/rdna/adverse_event_oba.html. 
11 DATA AND SAFETY MONITORING 
The RPCI Data and Safety Monitoring Board will assess the progress of the study, the safety 
data, and critical efficacy endpoints. The DSMB will review the study annually and will make 
recommendations that include but not limited to; (a) continuation of the study, (b) modifications 
to the design (c) or termination of the study. 
12 STATISTICAL METHODOLOGY 
The primary objective of this study is to assess immune-modulatory systemic and intratumoral 
effects of AGS-003 as neoadjuvant treatment in patients with localized renal cell carcinoma. 
The time component will be modeled as a three-level classification factor. The full model for the 
effects of time will be fit using Linear Mixed Model methods. The model will include a random 
patient effect and 5 fixed effects for time and the interactions. The presence of any time effect 
will be assessed with full-reduced model Type 3 test. If the omnibus test is statistically 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 41 of 46 
 
significant at the p < 0.05 level, then three pairwise time-point comparisons will be conducted. 
Expression measurements may be transformed to satisfy modeling assumptions. This 
methodology accommodates patients with incomplete follow-up information. 
Patient, disease and treatment characteristics will be summarized using common descriptive 
statistics and graphical aids. P values less than 0.05 will be deemed statistically significant. No 
adjustments will be made to control the overall Type I error rate. 
12.1 Sample Size Determination 
A maximum of 10 patients will be enrolled in this study. In previous experiments, immune 
marker expression measurements varied widely, with means between 8.0 and 1,200; the 
coefficient of variation has been between 0.5 and 1.0 depending on the marker, method of 
measurement and disease setting. For power calculations, the possible effect of immunotherapy 
delivery model of expression has been ignored, and the (original scale) expressions are assumed 
to have mean (standard deviation) of 100 (75), and within-patient correlation = 0.50. If the 
measurements are log-normally distributed, the log-transformed outcome would have mean 
(standard deviation) of about 4.38 (0.68). 
Comparing measurements at two time points, the within-patient effect of immunotherapy on an 
immune marker can be assessed using a permutation paired t-test. A paired t-test with a 
two-sided significance threshold of 0.05 has 80% power to detect a mean of at least 5.08 in the 
post-measurements, if the pre-measurements are as described above: a 20% increase in the mean 
on the original scale. 
12.2 Efficacy Analysis 
The efficacy analysis discussed above will be conducted using all patients with at least two time 
point measurements.  
12.3 Safety Analysis 
Adverse event rates will be summarized in all patients who received AGS-003. These rates will 
be described as the proportion of patients with the event, by grade, and supported with exact 95% 
confidence intervals. 
12.4 Stopping Rule: 
If during the trial 4 or more patients experience the undesirable event defined as unexpected 
bleeding or more difficult than usual perinephric dissection, accrual will be halted and the 
treatment will be deemed unsafe. Otherwise the accrual will continue for a total of 10 patients. 
The probability of excising the stopping rule within this study is a function of the true unknown 
probability of the event corresponding to the study population. The table below contains the 
probability of observing at least 4 undesirable events in the 10 patients for a variety of values of 
the true probability within the population. 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 42 of 46 
 
True probability of 
undesirable event 
0.2 
0.3 
0.4 
0.5 
Probability 
of 
exercising 
the 
stopping rule 
0.12 
0.35 
0.62 
0.83 
The calculations above are based on the assumption that our study sample may be treated as a 
random sample from the population of interest. 
12.5 Interim Analysis and Criteria for Early Termination of the Study 
No explicit interim analyses are planned for this study, given the low stage and slow growth rate 
of this type of cancer. 
13 CORRELATIVE DATA ANALYSIS 
Immune parameters will be assessed to demonstrate the effect of AGS-003 on the immune 
system. Immune effector cell populations will be assessed in a very detailed fashion and will 
focus on those populations that were found to be of interest in previous studies with AGS-003. 
Therefore, this study will analyze CD8+CD28+ T cells (REHA), In addition, this study will 
analyze T-regulatory cells (CD4+CD25+FoxP3+) and myeloid derived suppressor cells (MDSC) 
using multicolor flow cytometry. These cell populations will be assessed in peripheral blood 
specimens as well as in tumor lysates. The serum cytokine microenvironment will be assessed 
using multiplex Th1/Th2 cytokine ELISA (this will include IL-12 and IFN-γ). If perinephric 
lymph nodes are removed as standard of care during the kidney surgery, these will be procured 
and analyzed in a similar fashion. Autologous T cells will be incubated with irradiated 
autologous tumor cells and T cell proliferation will be measured in IFN-γ ELISPOT assays. 
After appropriate tumor tissue has been procured to assure pathologic diagnosis, tumors will be 
processed into tumor lysates. These lysates will be analyzed using flow cytometry as described 
above. The tumor infiltrating immune cell populations and tumor cytokine microenvironment 
will be assessed using standard double-staining immunohistochemistry. These results will be 
compared to a historical control tissue microarray (TMA) that contains 264 RCC specimens. 
14 ETHICAL AND REGULATORY STANDARDS 
14.1 Ethical Principles 
This study will not be initiated until the protocol and informed consent document(s) have been 
reviewed and approved by a properly constituted Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC). Each patient (or legal guardian) shall read, understand, 
and sign an instrument of informed consent prior to performance of any study-specific 
procedure. It is the responsibility of the investigator to ensure that the patient is made aware of 
the investigational nature of the treatment and that informed consent is given. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 43 of 46 
 
The Investigator is responsible for the retention of the patient log and patient records; although 
personal information may be reviewed by authorized persons, that information will be treated as 
strictly confidential and will not be made publicly available. The investigator is also responsible 
for obtaining patient authorization to access medical records and other applicable study specific 
information according to Health Insurance Portability and Accountability Act regulations (where 
applicable). 
This study will be conducted in compliance with all applicable laws and regulations of the state 
and/or country and institution where the patient is treated. The clinical trial should be conducted 
in accordance with the ethical principles embodied in the Belmont Report: Ethical Principles and 
Guidelines for the Protection of Human Subjects of Research, consistent with good clinical 
practice and the applicable regulatory requirements and according to the guidelines in this 
protocol, including attached appendices 
14.2 Informed Consent 
The Investigator is responsible for obtaining written consent from each patient or the patient's 
legally authorized representative in accordance with GCP guidelines using the approved 
informed consent form, before any study specific procedures (including screening procedures) 
are performed. The informed consent form acknowledges all information that must be given to 
the patient according to applicable GCP guidelines, including the purpose and nature of the 
study, the expected efficacy and possible side effects of the treatment(s), and specifying that 
refusal to participate will not influence further options for therapy. Any additional information 
that is applicable to the study must also be included. Additional national or institutionally 
mandated requirements for informed consent must also be adhered to. The patient should also be 
made aware that by signing the consent form, processing of sensitive clinical trial data and 
transfer to other countries for further processing is allowed. 
The Investigator shall provide a copy of the signed consent form to the patient and the signed 
original shall be maintained in the Investigator File. A copy of the signed consent form must be 
filed in the patient file. At any stage, the patient may withdraw from the study and such a 
decision will not affect any further treatment options. 
15 STUDY RESPONSIBILITIES 
15.1 Data Collection 
Data entry into the database is to be completed in a timely fashion within 30 days after the 
patient’s clinic visit. If an AE is considered serious it is captured on both the Adverse Event page 
and the Serious Adverse Event Source Form, which is handled in an expedited fashion. 
Data management activities will be performed using eClinical. eClinical is a suite of software 
tools that enables the collection, cleaning and viewing of clinical trial data. CRS data 
management will design the study-specific database and facilitate its development by the 
eClinical Information Technology team. Once the database design is approved by the 
Investigator, Statistician, and Clinical Research Coordinator, the database will be put into 
production and data entry can begin. Data can be entered and changed only by those with the 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 44 of 46 
 
rights to do so into electronic case report forms (eCRFs). eClinical is compliant with all technical 
aspects of relevant GCP guidelines. 
• The system can generate accurate copies of stored data and audit trail information in 
human readable form. 
• System access is limited to authorized individuals through the controlled assignment 
of unique ID and password combinations. 
• The system is designed to periodically force users to change their passwords and 
verifies that user ID and password combinations remain unique. 
• The system automatically generates a permanent time-stamped audit trail of all user 
interactions. 
When data entry is complete, data management will review the data and will query any missing, 
incomplete, or invalid data points for resolution by the Clinical Research Coordinator and 
Investigator. Once all queries have been resolved, the data can be released to the statistician for 
analysis. 
15.2 Maintenance of Study Documents 
Essential documents should be retained per RPCI’s policy for 6 years from the study termination 
date. These documents could be retained for a longer period, however, if required by the 
applicable local regulatory requirements or by an agreement with RPCI.  
16 ADMINISTRATIVE RULES 
16.1 Revisions to the Protocol 
RPCI may make such changes to the protocol as it deems necessary for safety reasons or as may 
be required by the U.S. FDA or other regulatory agencies. Revisions will be submitted to the 
IRB/ERC for written approval before implementation. 
16.2 Termination of the Study 
It is agreed that, for reasonable cause, either the RPCI Investigator or the AGS-003 manufacturer 
(Argos), may terminate this study, provided a written notice is submitted within the time period 
provided for in the Clinical Trial Agreement. In addition, RPCI may terminate the study at any 
time upon immediate notice if it believes termination is necessary for the safety of patients 
enrolled in the study. 
16.3 Confidentiality 
Any data, specimens, forms, reports, video recordings, and other records that leave the site will 
be identified only by a participant identification number (Participant ID, PID) to maintain 
confidentiality. All records will be kept in a limited access environment. All computer entry and 
networking programs will be done using PIDs only. Information will not be released without 
written authorization of the participant. 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 45 of 46 
 
 
17 APPENDICES 
Appendix A ECOG Performance Status Scores 
Description 
Status 
Fully active, able to carry on all pre-disease performance without restriction. 
0 
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. 
1 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
2 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
3 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
4 
Dead 
5 
 
 

Roswell Park Cancer Institute Study Number: I 250113 
 
PRIVATE AND CONFIDENTIAL INFORMATION OF ROSWELL PARK CANCER INSTITUTE 
 03/13/2017 
Page 46 of 46 
 
18 REFERENCES 
1. 
2010. AJCC Cancer Staging Manual. 7th ed. New York: Springer 
2. 
American Cancer Society.  
3. 
Schwaab T, Ernstoff MS. 2011. Therapeutic vaccines in renal cell carcinoma. Therapy 4: 
369-77 
4. 
Schwaab T, Atzpodien J. 2000. Renal Cell Carcinoma. In Strategies in Immunoadjuvant 
Therapies, ed. J Kirkwood: Dunitz 
5. 
Coates PT, Colvin BL, Hackstein H, Thomson AW. 2002. Manipulation of dendritic cells 
as an approach to improved outcomes in transplantation. Expert Rev Mol Med 4: 1-21 
6. 
Cesana GC, DeRaffele G, Cohen S, Moroziewicz D, Mitcham J, Stoutenburg J, Cheung 
K, Hesdorffer C, Kim-Schulze S, Kaufman HL. 2006. Characterization of CD4+CD25+ 
regulatory T cells in patients treated with high-dose interleukin-2 for metastatic 
melanoma or renal cell carcinoma. J Clin Oncol 24: 1169-77 
7. 
DeBenedette MA. 2010. Potency of dendritic cell based immunotherapies is correlated 
with IL-12 production by tracking the induction of multi-functional CD8+/CD28+ 
cytotoxic T cell immunity. ed. MA DeBenedette: CDTINCHD 
8. 
DeBenedette MA, Calderhead DM, Tcherepanova IY, Nicolette CA, Healey DG. 2011. 
Potency of mature CD40L RNA electroporated dendritic cells correlates with IL-12 
secretion by tracking multifunctional CD8(+)/CD28(+) cytotoxic T-cell responses in 
vitro. J Immunother 34: 45-57 
9. 
DeBenedette MA, Calderhead DM, Ketteringham H, Gamble AH, Horvatinovich JM, 
Tcherepanova IY, Nicolette CA, Healey DG. 2008. Priming of a novel subset of CD28+ 
rapidly expanding high-avidity effector memory CTL by post maturation electroporation-
CD40L dendritic cells is IL-12 dependent. J Immunol 181: 5296-305 
10. 
Tcherepanova IY, Adams MD, Feng X, Hinohara A, Horvatinovich J, Calderhead D, 
Healey D, Nicolette CA. 2008. Ectopic expression of a truncated CD40L protein from 
synthetic post-transcriptionally capped RNA in dendritic cells induces high levels of IL-
12 secretion. BMC Mol Biol 9: 90 
11. 
Schwaab T, Schwarzer A, Wolf B, Crocenzi TS, Seigne JD, Crosby NA, Cole BF, Fisher 
JL, Uhlenhake JC, Mellinger D, Foster C, Szczepiorkowski ZM, Webber SM, Schned 
AR, Harris RD, Barth RJ, Jr., Heaney JA, Noelle RJ, Ernstoff MS. 2009. Clinical and 
immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with 
Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma 
patients. Clin Cancer Res 15: 4986-92