A Phase 1/2, Open-Label, Multiple Ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion to Second Line Cervical Cancer
Phase: PHASE1
Conditions: Advanced Cancer, Cervical Cancer
Sponsor: Agenus Inc.

Agenus, Inc. C-700-01 
Phase 1/2 Trial of AGEN2034 in Advanced Tumors 
Amendment 5, 27 September 2019 
Confidential 
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Clinical Trial Protocol 
Clinical Trial Protocol Number 
C-700-01
Title 
A Phase 1/2, Open-Label, Multiple Ascending Dose Trial to 
Investigate the Safety, Tolerability, Pharmacokinetics, 
Biological, and Clinical Activity of AGEN2034 in Subjects 
with Metastatic or Locally Advanced Solid Tumors, with 
Expansion to Second Line Cervical Cancer 
Short Trial Name 
Phase 1/2 Study of AGEN2034 in Advanced Tumors 
Trial Phase 
Phase 1/2 
Medical Monitor 
 
Sponsor 
Agenus Inc. 
Original Protocol: 
26 October 2016  
Amendment 1: 
07 December 2016  
Amendment 2: 
11 January 2017 
Amendment 3: 
26 September 2017 
Amendment 4: 
24 January 2019 
Amendment 5: 
27 September 2019 
— Confidential —  
This document is the property of Agenus Inc. It is intended for restricted use only and may not be passed on, 
reproduced, published, or used in full or in part without the permission of Agenus. 
NCT #: NCT03104699

Agenus, Inc. C-700-01 
Phase 1/2 Trial of AGEN2034 in Advanced Tumors 
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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................8 
LIST OF FIGURES .........................................................................................................................8 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................9 
SYNOPSIS ....................................................................................................................................12 
1. 
INTRODUCTION AND RATIONALE .....................................................................21 
1.1. 
PD-1 Checkpoint Blockade ........................................................................................21 
1.1.1. 
PD-1 Pathway Blockade .............................................................................................21 
1.1.2. 
AGEN2034 .................................................................................................................22 
1.1.2.1. 
Summary of Preclinical Data ......................................................................................22 
1.1.2.2. 
Summary of Clinical Data ..........................................................................................24 
1.1.3. 
Safety of Nivolumab ...................................................................................................24 
1.1.3.1. 
Common Adverse Reactions of Nivolumab ...............................................................24 
1.1.3.2. 
Notable Immune-Mediated Adverse Reactions of Nivolumab ..................................25 
1.2. 
Rationale for Dose Selection ......................................................................................25 
1.2.1. 
Starting Dose in Phase 1 .............................................................................................25 
1.2.2. 
Dose in Phase 2 ...........................................................................................................27 
1.3. 
Rationale for Expansion Cohort .................................................................................28 
1.4. 
Rationale for Biomarker Assessment .........................................................................29 
1.4.1. 
Biomarkers in Phase 1 ................................................................................................29 
1.4.2. 
Biomarkers in Phase 2 ................................................................................................29 
1.4.3. 
Assessment of PD-L1 Expression in Tumors .............................................................29 
2. 
OBJECTIVES, ENDPOINTS, AND BENEFIT/RISK ..............................................30 
2.1. 
Objectives and Endpoints ...........................................................................................30 
2.1.1. 
Phase 1 ........................................................................................................................30 
2.1.2. 
Phase 2 ........................................................................................................................31 
2.2. 
Overall Risk/Benefit Assessment ...............................................................................32 
3. 
INVESTIGATIONAL PLAN .....................................................................................33 
3.1. 
Phase 1 (Part A): Dose Escalation ..............................................................................33 
3.1.1. 
Dose-Limiting Toxicity ..............................................................................................35 
3.1.2. 
Stopping Rules for Toxicity........................................................................................36 

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3.1.3. 
Backfill Expansion Enrollment for Each Dose Level Cohort in the Phase 1 .............36 
3.2. 
Phase 2: Dose Expansion Phase .................................................................................37 
3.3. 
Planned Number of Subjects ......................................................................................38 
3.3.1. 
Enrollment Targets .....................................................................................................38 
3.3.2. 
Subject Replacement Strategy ....................................................................................38 
3.4. 
Planned Trial Duration ...............................................................................................38 
3.5. 
Definition of End of Trial ...........................................................................................38 
3.6. 
Medical Care of Subjects After End of Trial ..............................................................38 
4. 
SELECTION OF TRIAL POPULATION..................................................................39 
4.1. 
Target Population ........................................................................................................39 
4.2. 
Inclusion Criteria ........................................................................................................39 
4.3. 
Exclusion Criteria .......................................................................................................41 
4.4. 
Criteria for Subject Withdrawal ..................................................................................43 
4.4.1. 
Withdrawal from Treatment .......................................................................................43 
4.4.2. 
Withdrawal from the Trial ..........................................................................................45 
4.4.3. 
Premature Discontinuation of the Trial ......................................................................46 
5. 
STUDY DRUGS AND TREATMENT......................................................................46 
5.1. 
Investigational Medicinal Product ..............................................................................46 
5.2. 
Packaging and Labeling ..............................................................................................47 
5.3. 
Storage and Dispensing ..............................................................................................47 
5.4. 
Dosage and Administration ........................................................................................48 
5.4.1. 
AGEN2034 .................................................................................................................48 
5.4.1.1. 
Treatment Regimen ....................................................................................................48 
5.4.2. 
Premedication .............................................................................................................48 
5.4.3. 
Treatment of Infusion Related Reactions ...................................................................48 
5.4.4. 
Dose Modifications and Treatment Delay ..................................................................52 
5.4.4.1. 
Dose Reductions .........................................................................................................52 
5.4.4.2. 
Treatment Delay .........................................................................................................52 
5.4.5. 
Treatment Beyond Disease Progression .....................................................................53 
5.5. 
Concomitant Treatments .............................................................................................54 
5.5.1. 
Acceptable Concomitant Medications ........................................................................54 
5.5.1.1. 
Rescue Medications and Supportive Care ..................................................................54 
5.5.2. 
Prohibited and/or Restricted Treatments ....................................................................55 

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5.5.3. 
Other Restrictions and Precautions .............................................................................56 
5.6. 
Management of Immune-related Adverse Events ......................................................56 
5.6.1. 
Dermatological Immune-related Adverse Events .......................................................57 
5.6.2. 
Gastrointestinal Immune-related Adverse Events ......................................................58 
5.6.3. 
Pulmonary Immune-related Adverse Events ..............................................................59 
5.6.4. 
Hepatic Immune-related Adverse Events ...................................................................60 
5.6.5. 
Endocrine Immune-related Adverse Events ...............................................................61 
5.6.6. 
Renal Immune-related Adverse Events ......................................................................62 
5.6.7. 
Neurological Immune-related Adverse Events ...........................................................63 
6. 
TRIAL ASSESSMENTS AND PROCEDURES .......................................................64 
6.1. 
Phase 1 Schedules of Assessments and Procedures ...................................................64 
6.2. 
Phase 2 Schedule of Assessments and Procedures .....................................................70 
6.3. 
Visit Requirements .....................................................................................................75 
6.3.1. 
Screening ....................................................................................................................75 
6.3.2. 
Treatment Phase ..........................................................................................................75 
6.3.3. 
End-of-Treatment Visits .............................................................................................75 
6.3.3.1. 
Discontinuation Visit ..................................................................................................75 
6.3.3.2. 
Safety Follow-up Visit ................................................................................................75 
6.3.4. 
Follow-up Phase .........................................................................................................75 
6.3.4.1. 
Follow-up Visits .........................................................................................................76 
6.3.4.2. 
Survival Follow-up (Phase 2 only) .............................................................................76 
6.4. 
Trial Procedures ..........................................................................................................76 
6.4.1. 
Administrative Procedures ..........................................................................................76 
6.4.1.1. 
Informed Consent .......................................................................................................76 
6.4.1.2. 
General Informed Consent ..........................................................................................76 
6.4.1.3. 
Consent for Pharmacogenomics Assessment (optional) .............................................77 
6.4.1.4. 
Review of Inclusion and Exclusion Criteria ...............................................................77 
6.4.1.5. 
Emergency Medical Support and Subject Card ..........................................................77 
6.4.1.6. 
Medical History ..........................................................................................................78 
6.4.1.7. 
Review of Baseline Symptoms ...................................................................................78 
6.4.1.8. 
Review of Prior and Concomitant Medications ..........................................................78 
6.4.1.9. 
Cancer Disease Details and Prior Treatment ..............................................................78 
6.4.1.10. 
Assignment of Subject Trial Number .........................................................................79 

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6.4.1.11. 
Trial Compliance ........................................................................................................79 
6.4.2. 
Tissue Collection and Tumor Biomarker Assessment ................................................80 
6.4.2.1. 
Tissue Collection ........................................................................................................80 
6.4.2.2. 
PD-L1 Expression Assessment ...................................................................................81 
6.4.2.3. 
HPV Assessment ........................................................................................................81 
6.4.3. 
Clinical Assessments and Procedures .........................................................................81 
6.4.3.1. 
Review of Adverse Events..........................................................................................81 
6.4.3.2. 
Physical Examination .................................................................................................82 
6.4.3.3. 
Vital Signs, Height and Weight ..................................................................................82 
6.4.3.4. 
12-lead Electrocardiogram ..........................................................................................82 
6.4.3.5. 
Expanded Electrocardiogram Evaluation (in selected sites only) ..............................82 
6.4.3.6. 
Eastern Cooperative Oncology Group Performance ..................................................83 
6.4.4. 
Imaging Assessments ..................................................................................................83 
6.4.4.1. 
Tumor Imaging ...........................................................................................................83 
6.4.4.2. 
Brain Imaging .............................................................................................................83 
6.4.4.3. 
Response Assessment .................................................................................................84 
6.4.5. 
Pharmacokinetic, Pharmacodynamic, Genetic, and Other Assessments ....................85 
6.4.5.1. 
Pharmacokinetic Assessments ....................................................................................85 
6.4.5.2. 
Immunogenicity Assessment ......................................................................................85 
6.4.5.3. 
Blood Biomarker Assessments ...................................................................................85 
6.4.5.4. 
Pharmacogenomics Assessments (Optional) ..............................................................87 
6.4.6. 
Local Laboratory Tests ...............................................................................................87 
7. 
ADVERSE EVENTS..................................................................................................89 
7.1. 
Adverse Event Definitions ..........................................................................................89 
7.1.1. 
Adverse Event .............................................................................................................89 
7.1.2. 
Abnormal Laboratory Findings and Other Abnormal Investigational 
Findings ......................................................................................................................90 
7.1.3. 
Adverse Drug Reaction ...............................................................................................90 
7.1.4. 
Serious Adverse Event ................................................................................................90 
7.1.5. 
Events That Do Not Meet the Definition of an SAE ..................................................90 
7.1.6. 
Events not to be Considered as AEs/SAEs .................................................................91 
7.1.7. 
AE/SAEs Observed in Association with Disease Progression ...................................91 
7.1.8. 
Predefined Potential AEs of Special Interest for Safety Monitoring ..........................91 

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7.2. 
Methods of Recording and Assessing Adverse Events ..............................................92 
7.2.1. 
Definition of the Adverse Event Reporting Period .....................................................92 
7.2.2. 
Procedure for Reporting SAEs / AESIs ......................................................................92 
7.2.2.1. 
Serious Adverse Events ..............................................................................................92 
7.2.2.2. 
Adverse Events of Special Interest .............................................................................93 
7.2.2.3. 
Safety Reporting to Health Authorities, Independent Ethics Committees/ 
Institutional Review Boards, and Investigators ..........................................................93 
7.3. 
Monitoring of Subjects with Adverse Events .............................................................94 
7.4. 
Pregnancy and In Utero Drug Exposure .....................................................................94 
7.5. 
AGEN2034 Overdose .................................................................................................95 
8. 
STATISTICAL CONSIDERATIONS .......................................................................95 
8.1. 
Sample Size ................................................................................................................95 
8.1.1. 
Phase 1 ........................................................................................................................95 
8.1.2. 
Phase 2 ........................................................................................................................95 
8.2. 
Analysis Sets ...............................................................................................................96 
8.3. 
Description of Statistical Analyses .............................................................................96 
8.3.1. 
General Considerations ...............................................................................................96 
8.3.2. 
Analysis of Primary Endpoints ...................................................................................97 
8.3.2.1. 
In Phase 1: Dose-limiting Toxicity .............................................................................97 
8.3.2.2. 
In Phase 2: Objective Response Rate .........................................................................97 
8.3.3. 
Analysis of Secondary Endpoints ...............................................................................97 
8.3.3.1. 
Efficacy Parameters ....................................................................................................97 
8.3.3.2. 
Pharmacokinetic Parameters .......................................................................................98 
8.3.3.3. 
Immunogenicity ..........................................................................................................98 
8.3.3.4. 
Exploratory Biomarkers ..............................................................................................98 
8.3.4. 
Safety Analyses ..........................................................................................................98 
8.3.4.1. 
Adverse Events ...........................................................................................................99 
8.3.4.2. 
Laboratory Variables ..................................................................................................99 
8.3.4.3. 
Physical Examination, Vital Signs, and Electrocardiogram .......................................99 
8.3.5. 
Interim and Final Analysis..........................................................................................99 
9. 
TRIAL GOVERNANCE AND OVERSIGHT .........................................................100 
9.1. 
Safety Monitoring Committee ..................................................................................100 
9.2. 
Independent Endpoint Review Committee ...............................................................100 

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9.3. 
Independent Data Monitoring Committee (IDMC) ..................................................101 
10. 
ETHICAL AND REGULATORY ASPECTS .........................................................101 
10.1. 
Ethics Review ...........................................................................................................101 
10.2. 
Responsibilities of the Investigator ..........................................................................102 
10.3. 
Subject Information and Informed Consent .............................................................102 
10.4. 
Subject Identification and Privacy ............................................................................102 
10.5. 
Emergency Medical Support and Subject Card ........................................................103 
10.6. 
Clinical Trial Insurance and Compensation to Subjects ...........................................104 
10.7. 
Health Authorities .....................................................................................................104 
11. 
TRIAL MANAGEMENT .........................................................................................104 
11.1. 
Sponsor and Trial Administrative Structure .............................................................104 
11.2. 
Investigational Sites ..................................................................................................104 
11.3. 
Trial Coordination/Monitoring .................................................................................104 
11.4. 
Data Collection .........................................................................................................105 
11.5. 
Investigator Site File and Archiving .........................................................................105 
11.6. 
Monitoring, Quality Assurance and Inspection by Health Authorities ....................105 
11.7. 
Publication Policy .....................................................................................................106 
11.7.1. 
Clinical Trial Report .................................................................................................106 
11.7.2. 
Publications ...............................................................................................................106 
12. 
REFERENCES .........................................................................................................107 
APPENDIX 1. .................. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
SCALE ......................................................................................................................110 
APPENDIX 2. ........................ SIGNATURE PAGES AND RESPONSIBLE PERSONS FOR THE 
TRIAL .......................................................................................................................111 
 

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LIST OF TABLES 
Table 1: AGEN2034 Starting Dose Calculations ..........................................................................26 
Table 2: Phase 1 Dosing Regimens ...............................................................................................48 
Table 3: AGEN2034 Infusion Related Reaction Management Guidelines ...................................51 
Table 4: Dermatological Immune-related Adverse Event Management Algorithm ......................57 
Table 5: Gastrointestinal Immune-related Adverse Event Management Algorithm .....................58 
Table 6: Pulmonary Immune-related Adverse Event Management Algorithm .............................59 
Table 7: Hepatic Immune-related Adverse Event Management Algorithm ..................................60 
Table 8: Endocrine Immune-related Adverse Event Management Algorithm ..............................61 
Table 9: Renal Immune-related Adverse Event Management Algorithm .....................................62 
Table 10: Neurological Immune-related Adverse Event Management Algorithm ........................63 
Table 11: Phase 1 Part A1 — Schedule of Assessments and Procedures ...................................64 
Table 12: Phase 1 Part A2 — Schedule of Assessments and Procedures ...................................67 
Table 13: Phase 2 — Schedule of Assessments and Procedures ................................................71 
Table 14: Phase 2 — Blood Sampling for Pharmacokinetic, Pharmacodynamic, 
Genetic, and Other Assessments .................................................................................74 
Table 15: Required Local Laboratory Panel Tests ........................................................................88 
 
LIST OF FIGURES 
Figure 1: In vitro Comparability of AGEN2034 and Nivolumab ..................................................23 
Figure 2: Phase 1 Dose Escalation Schematic ...............................................................................35 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviation or Specialist Term 
Explanation 
ACTH 
adrenocorticotropic hormone 
ADA 
anti-drug antibody; in this trial, antibody against AGEN2034 
ADL 
activities of daily living 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
AJCC-8 
American Joint Committee on Cancer Staging Manual, 8th edition 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the drug concentration-time curve 
AUC0-∞  
area under the drug concentration-time curve from time of dosing (0 h) 
extrapolated to infinity 
AUC0-t  
area under the drug concentration-time curve from time of dosing (0 h) to 
time t (typically time of last observation) 
AUC(t1-t2)-ss 
area under the drug concentration-time curve within the time span t1 to time 
t2 at steady-state 
BOR 
best overall response 
BUN 
blood urea nitrogen 
C 
Celsius 
CI 
confidence interval 
Cmax  
maximum drug concentration observed postdose 
CNS 
central nervous system 
CR 
complete response 
CRO 
contract research organization 
CRP 
C-reactive protein 
CT  
computed tomography  
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T lymphocyte antigen-4 
dL 
deciliter 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
FDA 
United States Food and Drug Administration 
FFPE 
formalin-fixed paraffin embedded 
FSH 
follicle-stimulating hormone 
g 
gram 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
h 
hour(s) 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 

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Abbreviation or Specialist Term 
Explanation 
ICH 
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use) 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IERC 
Independent Endpoint Review Committee 
IgG4 
immunoglobulin G4 
IgG4κ 
immunoglobulin G4 antibodies with immunoglobulin kappa light chains 
IL 
interleukin 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
irAE 
immune-related adverse event 
IRB 
Institutional Review Board 
IULN 
institutional upper limit of normal 
IV 
intravenous 
kg 
kilogram 
L 
liter 
lb 
pound 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
λz  
terminal elimination rate constant 
m 
month 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
µg 
microgram 
mg 
milligram 
min 
minute 
mL 
milliliter 
mm 
millimeter 
mM 
millimolar 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute  
nM 
nanomolar 
NSAID 
nonsteroidal anti-inflammatory drug 
NSCLC 
non–small-cell lung cancer  
ORR 
objective response rate 
OS 
overall survival  
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamic, or progressive disease 
PD-1 
programmed cell death protein 1 
PD-L1/-L2 
ligand 1 or 2 of programmed cell death protein 1  
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PO 
oral, or by mouth 
PR 
partial response 
q 
each, every 
Q 
calendar quarter 
RBC 
red blood cell 
RCC 
renal cell carcinoma 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RNA 
ribonucleic acid 

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Abbreviation or Specialist Term 
Explanation 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
SEA 
Staphylococcus enterotoxin A 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SHP-1/-2 
Src homology region 2 domain–containing phosphatase 1 or 2 
SMC 
Safety Monitoring Committee 
t½  
half-life 
T4 
free thyroxine 
TCR 
T cell receptor 
TEAE 
treatment-emergent adverse event 
tmax  
time to reach maximum concentration 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
V 
visit 
wk 
week(s) 
WBC 
white blood cell 
 
 

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SYNOPSIS 
Trial Title 
A Phase 1 / 2, Open-Label, Multiple Ascending Dose Trial to Investigate the Safety, 
Tolerability, Pharmacokinetics, Biological, and Clinical Activity of AGEN2034 in 
Subjects with Metastatic or Locally Advanced Solid Tumors, with Expansion to Second 
Line Cervical Cancer 
Trial Number 
C-700-01 
Names of Trial Drug 
AGEN2034 
Sponsor 
Agenus Inc., 3 Forbes Road, Lexington, MA 02421, USA 
Phase 
1 / 2 
Trial Centers/ 
Countries 
Phase 1: approximately 10-15 enrolling centers globally 
Phase 2: approximately 60 enrolling centers globally 
Estimated Trial Period 
First subject in: 2Q 2017  
Last subject out: 2Q 2022 
Objectives 
Phase 1: 
Primary Objective 
 • 
To assess the safety and tolerability of AGEN2034 in subjects with metastatic 
and/or locally advanced solid tumors 
Secondary Objectives 
• 
To characterize the AGEN2034 pharmacokinetic (PK) profile 
• 
To correlate AGEN2034 exposure with target occupancy 
• 
To evaluate the immunogenicity of AGEN2034 and correlate it to exposure 
Exploratory Objectives 
• 
• 
To explore the association of programmed cell death protein 1 – ligand 1 (PD-L1) 
expression with clinical responses 
Phase 2: 
Primary Objective 
 • 
To assess objective response rate (ORR) according to RECIST 1.1 as determined 
by an Independent Endpoint Review Committee (IERC) 
Secondary Objectives 
• 
To assess the safety and tolerability of AGEN2034 in subjects with metastatic 
and/or locally advanced solid tumors 
• 
To characterize the AGEN2034 PK profile 
• 
To evaluate the immunogenicity of AGEN2034 and correlate it to exposure 
• 
To assess ORR according to RECIST 1.1 as determined by investigator 
• 
To assess duration of response (DOR), disease control rate (DCR), duration of 
stable disease (SD), time to response, and progression-free survival (PFS) time per 
RECIST 1.1 
• 
To assess overall survival (OS) rate 
• 
To assess OS time 
Exploratory Objectives 
• 
• 
To explore the association of programmed cell death protein 1 – ligand 1 (PD-L1) 
expression with clinical outcomes 

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Endpoints 
Phase 1: 
Primary Endpoints 
• 
Occurrence of dose-limiting toxicities (DLTs) in subjects in dose escalation during 
the first 21 days of treatment 
• 
Frequency, severity, and duration of treatment-emergent AEs (TEAEs) and 
laboratory abnormalities using the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) v4.03. 
Secondary Endpoints 
• 
AGEN2034 PK parameters which may include (but are not limited to) maximum 
drug concentration observed postdose at steady-state (Cmax-ss), minimum observed 
concentration at steady-state (Cmin-ss), area under the drug concentration-time curve 
within time span t1 to t2 at steady-state (AUC(t1-t2)-ss), area under the drug 
concentration-time curve from time zero to time t (AUC(0-t)), area under the drug 
concentration-time curve from time zero to infinity (AUC(0-∞)), time to maximum 
observed concentration (tmax), terminal disposition rate constant (λz), terminal 
elimination half-life (t1/2), systemic clearance (CL), and volume of distribution (Vd) 
• 
Receptor occupancy on circulating T cells measured 4 hours after the 1st dose and 
immediately prior to the 2nd dose 
• 
Receptor occupancy saturation levels correlated with AGEN2034 PK exposure 
metrics 
• 
Antidrug antibody (ADA) concentrations and correlation with AGEN2034 PK 
exposure metrics 
Exploratory Endpoints 
• 
• 
• 
• 
Baseline expression of PD-L1 
Phase 2: 
Primary Endpoint 
 • 
Confirmed ORR per RECIST 1.1, as determined by an IERC, in the analysis 
population 
Secondary Endpoints 
• 
Frequency, severity, and duration of TEAEs and laboratory abnormalities, using 
NCI CTCAE v4.03 
 • 
AGEN2034 PK parameters which may include (but are not limited to) maximum 
drug concentration observed postdose at steady-state (Cmax-ss), minimum observed 
concentration at steady-state (Cmin-ss), area under the drug concentration-time curve 
within time span t1 to t2 at steady-state (AUC(τ1-τ2)-ss), area under the drug 
concentration-time curve from time zero to time t (AUC(0-t)), area under the drug 
concentration-time curve from time zero to infinity (AUC(0-∞)), time to maximum 
observed concentration (tmax), terminal disposition rate constant (λz), terminal 
elimination half-life (t1/2), systemic clearance (CL), and volume of distribution (Vd) 
• 
ADA concentrations and correlation with AGEN2034 PK exposure metrics 
• 
Confirmed ORR per RECIST 1.1, as determined by an investigator 
• 
DOR per RECIST 1.1, as determined by an IERC and investigator, defined as time 
from first observation of response to first observation of documented disease 
progression (or death within 12 weeks after last tumor assessment). Subjects 

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without an event at analysis cutoff date will be censored on date of last tumor 
assessment. 
• 
DCR, defined as proportion of subjects with complete response (CR), partial 
response (PR), or stable disease (SD) for at least 12 weeks 
• 
Duration of SD, measured from the start of treatment until the criteria for 
progression are met, taking as reference the smallest measurements recorded since 
the treatment started, including baseline measurements 
• 
Time to response, defined as the time from the first dose date to first observation of 
confirmed response 
• 
PFS time, defined as time from first treatment administration to first observation of 
documented disease progression (or death within 12 wk after last tumor 
assessment), per RECIST 1.1, as determined by an IERC and investigator. Subjects 
without an event at analysis cutoff date will be censored on date of last tumor 
assessment. 
• 
Median OS and OS rate 
• 
OS time, defined as time from start of treatment to death. For subjects who are still 
alive at time of data cutoff for trial analysis or who are lost to follow-up, survival 
will be censored at the last recorded date that the subject is known to be alive as of 
the cutoff date for analysis 
Exploratory Endpoints 
• 
• 
• 
Baseline expression of PD-L1 association with clinical outcomes 
Trial Design and Plan 
This is a 2-part trial: a Phase 1, open-label, dose-escalation trial in subjects with 
metastatic or locally advanced solid tumors, with a consecutive Phase 2 expansion to 
evaluate efficacy in subjects with recurrent, unresectable, or metastatic (advanced) 
cervical cancer that has progressed after a platinum-based treatment regimen. 
Phase 1: Dose Escalation 
Phase 1 will consist of a standard 3+3 dose escalation with the following escalating dose 
levels and schedules: 
 
Part A1: 1, 3, and 10 mg/kg administered every 2 weeks 
 
Part A2: 6 and 10 mg/kg administered every 3 weeks 
Each subject will stay on the dose level and schedule assigned at trial entry. Subjects 
will receive AGEN2034 for a maximum of 24 months or until progression, 
unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from 
the trial occurs. 
A Safety Monitoring Committee (SMC) will assess safety; decide on dose-escalation 
and opening of backfill enrollment; define the recommended Phase 2 dose (RP2D); and 
determine opening of the Phase 2 cohorts. 
In Part A1, the first subject of each cohort will be observed for 16 days (i.e., ≥ 48 hours 
after second dose) for occurrence of DLT before the second subject is administered trial 
medication. Thereafter, within each cohort, consecutively enrolled subjects may initiate 
treatment ≥ 48 hours after the prior enrolled subject initiated treatment. Dose escalation 
will continue until the maximum tolerated dose (MTD) is reached or the maximum 
planned dose level (10.0 mg/kg) is shown to be safe. The MTD is defined as the dose 
below which ≥ 2 DLTs are observed. 
Once Part A1 is completed, enrollment to Part A2 will begin. If < 2 DLTs are observed 
in Part A1 at the maximum planned dose of 10 mg/kg every 2 weeks, open enrollment 
to Part A2 will begin with enrollment of 10 subjects at 6 mg/kg every 3 weeks, followed 

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by open enrollment of 10 subjects at 10 mg/kg every 3 weeks. If ≥ 2 DLTs are observed 
in Part A1, at the maximum planned dose in Part A1, the standard 3+3 dose escalation 
will continue with Part A2 where consecutively enrolled subjects in dose escalation may 
initiate treatment ≥ 48 hours after the prior enrolled subject initiated treatment. 
For cohorts in dose escalation, concurrent with the 3+3 dose escalation schema, 
additional subjects will be backfilled to lower dose levels to ensure that each cohort 
enrolls at least 10 subjects. Subjects enrolled to backfill cohorts may be enrolled 
simultaneously, without sequential dosing (i.e., not required to wait 48 hours between 
2 subjects). These additional subjects at each dose level will have the purpose of 
generating additional safety, PK, and receptor occupancy data, and will not undergo 
formal DLT observation. 
Phase 2: Dose Expansion 
To further characterize safety and efficacy, subjects with recurrent, unresectable, or 
metastatic cervical cancer will be enrolled in Phase 2 and receive the RP2D of 
AGEN2034 (3 mg/kg every 2 weeks) for a maximum of 24 months or until progression, 
unacceptable toxicity, or any criterion for stopping the study drug or withdrawal from 
the trial occurs. 
An SMC will assess safety, and an Independent Data Monitoring Committee (IDMC) 
will evaluate safety and efficacy. 
Number of Subjects 
(Planned) 
Phase 1 (Parts A1 and A2): Approximately 50 subjects; final sample size may vary 
depending on the total number of dose levels to be tested, and subject replacement for 
DLT evaluation, if applicable 
Phase 2: Approximately 150 subjects with recurrent, unresectable, or metastatic 
cervical cancer.  
Trial Eligibility 
Inclusion Criteria: 
1. Voluntarily agree to participate by giving written informed consent. Participation in 
pharmacogenomics testing is optional. 
2. Be ≥ 18 years of age. 
3. Diagnosis and prior systemic treatment: 
a. 
Phase 1: Have a histologically or cytologically confirmed diagnosis of a 
metastatic or locally advanced solid tumor for which no standard therapy is 
available or standard therapy has failed. 
b. Phase 2:  
I.  Have (1) a histologically or cytologically confirmed diagnosis of 
squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma 
of the cervix, and (2) metastatic, locally advanced, and/or unresectable 
disease at the time of enrollment. Histologic confirmation of the original 
primary tumor is required via pathology report. 
 
Note: The following cervical tumors are not eligible: minimal 
deviation/adenoma malignum, gastric type adenocarcinoma, clear cell 
carcinoma, and mesonephric carcinoma.  
II.  Has cervical cancer and has relapsed after a platinum-based treatment (first 
line) regimen for advanced (recurrent, unresectable, or metastatic) disease;  
 
Note: Subject receiving chemotherapy concurrently with primary radiation 
(e.g., weekly cisplatin) or subject receiving adjuvant chemotherapy 
following completion of radiation therapy (e.g., paclitaxel and carboplatin 
for ≤ 4 cycles) and progressed within 6 months after treatment completion 
will be eligible as this systemic therapy will be considered as first-line 
treatment.  
4. Measurable disease – based on investigator assessment 

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a. 
Phase 1: Have objective evidence of disease; the presence of measurable 
disease is not required. 
b. Phase 2: Have measurable disease on imaging based on RECIST version 1.1. 
 
Note: Subjects must have at least one "target lesion" to be used to assess 
response, as defined by RECIST version 1.1. Tumors within a previously 
irradiated field will be designated as "non-target" lesions unless progression is 
documented or a biopsy is obtained to confirm persistence at least 90 days 
following completion of radiation therapy. 
       Note: Measurable disease by RECIST 1.1 must be confirmed by independent 
central radiologic review prior to first dose. Subjects without centrally 
confirmed measurable disease at baseline will not be eligible for this trial. 
5. Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology 
Group (ECOG) performance status of 0 or 1. 
6. Have adequate organ function as indicated by the following laboratory values: 
a. 
Adequate hematological function defined by absolute neutrophil count (ANC) 
≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and stable hemoglobin ≥ 8 g/dL 
(without transfusions within 1 week before first dose). 
b. Adequate hepatic function based by a total bilirubin level ≤ 1.5 x the 
institutional upper limit of normal (IULN), aspartate aminotransferase (AST) 
level ≤ 2.5 x IULN, alanine aminotransferase (ALT) level ≤ 2.5 x IULN, and 
alkaline phosphatase ≤ 2.5 x IULN. 
c. 
Adequate renal function defined as creatinine ≤ 1.5 x IULN OR calculated 
creatinine clearance ≥ 50 mL/min for subjects with creatinine levels > 1.5 x 
IULN (if no local guideline is available, creatinine clearance should be 
calculated using the Cockcroft-Gault Method). 
d. Adequate coagulation defined by international normalized ratio (INR) or 
prothrombin time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant 
therapy); and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN 
(unless the subject is receiving anticoagulant therapy) 
7. Other than the cancer for which the subject is enrolled, have no history of prior 
malignancy, with the exception of basal cell carcinoma of the skin, superficial 
bladder cancer, squamous-cell carcinoma of the skin, or has undergone potentially 
curative therapy with no evidence of that disease recurrence for 5 years since 
initiation of that therapy. 
8. In Phase 2, subjects must provide a sufficient and adequate formalin-fixed paraffin 
embedded (FFPE) tumor tissue sample preferably from the most recent biopsy of a 
tumor lesion, collected either at the time of or after the diagnosis of advanced or 
metastatic disease has been made AND from a site not previously irradiated. If no 
tumor tissue is available, a fresh biopsy will be required.  
 
Note: Tissue from needle or excisional biopsy or from resection is required. 
9. Female subjects must have a negative serum pregnancy test at screening (within 
72 hours before first dose of study drug) if of childbearing potential or be of non-
child bearing potential. Non-childbearing potential is defined as (by other than 
medical reasons): 
a. 
≥ 45 years of age and has not menstruated for greater than 1 year, 
b. Amenorrheic for < 2 years without a hysterectomy and oophorectomy and a 
follicle-stimulating hormone (FSH) value in the postmenopausal range upon 
pretrial (screening) evaluation, 
c. 
Whose status is post hysterectomy, oophorectomy or tubal ligation. 
10. If of childbearing potential, female subjects must be willing to use 2 highly 
effective methods (defined in the informed consent form [ICF]) throughout the 

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study, starting with the screening visit through 120 days after the last dose of study 
drug. 
 
Note: Abstinence is acceptable if this is the established and preferred contraception 
for the subject. 
11. Male subjects with a female partner(s) of child-bearing potential must agree to use 
2 highly effective methods (defined in the ICF) throughout the trial starting with the 
screening visit through 120 days after the last dose of study drug is received. Males 
with pregnant partners must agree to use a condom; no additional method of 
contraception is required for the pregnant partner. 
 
Note: Abstinence is acceptable if this is the established and preferred contraception 
for the subject. 
12. Is willing and able to comply with the requirements of the protocol. 
Exclusion Criteria: 
1. Is currently participating and receiving study therapy or has participated in a study 
of an investigational agent and received study therapy or used an investigation 
device within 4 weeks before the first dose of treatment. 
2. Has an inadequate washout period prior to first dose of study drug defined as:  
a. 
Received systemic cytotoxic chemotherapy or biological therapy within 
3 weeks before first dose, 
b. Received radiation therapy within 3 weeks before first dose, or 
c. 
Had major surgery within 4 weeks before first dose. 
3. Has received prior therapy with: 
a. 
Any antibody/drug targeting T-cell co-regulatory proteins (immune 
checkpoints) such as anti–PD-1, anti–PD-L1, or anti–cytotoxic T-lymphocyte 
antigen 4 (CTLA-4) antibodies 
b. For Phase 2: > 1 systemic treatment regimen for the advanced (recurrent, 
unresectable, or metastatic) cervical cancer for which the subject is considered 
for the study 
 
Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for 
subjects with metastatic melanoma. 
4. Has persisting toxicity related to prior therapy of NCI CTCAE Grade > 1 severity. 
 
Note: Sensory neuropathy or alopecia of Grade ≤ 2 is acceptable. 
5. Is expected to require any other form of systemic or localized antineoplastic therapy 
while on trial (including maintenance therapy with another agent, radiation therapy, 
and/or surgical resection). 
6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies 
(NCI CTCAE version 4.03 Grade ≥ 3), any history of anaphylaxis, or uncontrolled 
asthma. 
7. Is receiving systemic corticosteroid ≤ 7 days prior to the first dose of trial treatment 
or receiving any other form of systemic immunosuppressive medication 
(corticosteroid use on study for management of immune-related adverse events, 
and/or a premedication for IV contrast allergies/reactions is allowed). Subjects who 
are receiving daily corticosteroid replacement therapy are an exception to this rule. 
Examples of permitted therapy are daily prednisone at doses of 5 to 7.5 mg or 
equivalent hydrocortisone dose, and steroid therapy administered by topical, 
intraocular, intranasal, and/or inhalation routes. 
8. Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous 
meningitis identified either on the baseline brain imaging obtained during the 
screening period OR identified prior to consent. 

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Note: Subjects with history of brain metastases that have been treated may 
participate provided they show evidence of stable supra-tentorial lesions at 
screening (based on 2 sets of brain images, performed ≥ 4 weeks apart, and 
obtained after the brain metastases treatment). In addition, any neurologic 
symptoms that developed either as a result of the brain metastases or their treatment 
must have resolved or be minimal and be expected as sequelae from treated lesions. 
For individuals who received steroids as part of brain metastases treatment, steroids 
must be discontinued ≥ 7 days prior to first dose of study drug. 
9. Has active or history of autoimmune disease that has required systemic treatment 
within 2 years of the start of trial treatment (i.e., with use of disease modifying 
agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., 
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or 
pituitary insufficiency, etc.) is not considered a form of systemic treatment. 
 
Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid 
disease not requiring immunosuppressive treatment are eligible. 
10. Has had an allogeneic tissue/solid organ transplant. 
11. Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that 
has required oral or IV corticosteroids. 
12. Has an active infection requiring intravenous systemic therapy. 
13. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 
14. Has known active Hepatitis B, Hepatitis C or tuberculosis. Active Hepatitis B is 
defined as a known positive HBsAg result. Active Hepatitis C is defined by a 
known positive Hep C Ab result and known quantitative HCV RNA results greater 
than the lower limits of detection of the assay. 
15. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular 
accident/stroke or myocardial infarction within 6 months before enrollment, 
unstable angina, congestive heart failure (New York Heart Association class ≥ II), 
or serious uncontrolled cardiac arrhythmia requiring medication. 
16. Has a history or current evidence of any condition, therapy, or laboratory 
abnormality that might confound the results of the trial, interfere with the subject’s 
participation for the full duration of the trial, or is not in the best interest of the 
subject to participate, in the opinion of the treating Investigator. 
17. Has known psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the trial. 
18. Is, at the time of signing informed consent, a regular user (including “recreational 
use”) of any illicit drugs or had a recent history (within the last year) of substance 
abuse (including alcohol). 
19. Is legally incapacitated or has limited legal capacity. 
20. Is pregnant or breastfeeding or expecting to conceive or father children within the 
projected duration of the trial, starting with the screening visit through 120 days 
after the last dose of study drug. 
Dosage and 
Administration  
AGEN2034 is an IgG4 antibody designed to block PD-1. 
Dose Levels 
 
Phase 1: Part A1: 1, 3, and 10 mg/kg IV every 2 weeks 
 
 
 
 
 Part A2: 6 and 10 mg/kg IV every 3 weeks 
 
Phase 2: 3 mg/kg IV every 2 weeks 
Administration 
 
AGEN2034 will be administered IV over 60 minutes (-10/+20 min) 

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Planned Trial Duration  The maximum trial duration for a subject is estimated to be up to approximately 
49 months. This includes a screening period, a planned treatment period of up to 
approximately 24 months, and a follow-up period of up to 24 months after the last dose 
of study treatment. 
The overall trial duration is expected to be approximately 63 months. 
Schedule of Visits and 
Assessments  
Screening Period (Phase 1 and Phase 2) 
Screening assessments will be conducted within 42 days prior to first treatment dose, 
with associated evaluations and procedures. 
Treatment Phase (Phase 1 and Phase 2) 
The treatment phase is divided into 2-week (Phases 1 and 2) or 3-week (Phase 1) cycles 
with associated evaluations and procedures that must be performed at specific time 
points. Each cycle begins with the administration of AGEN2034. Subjects will be 
treated for up to 24 months or until disease progression, unacceptable toxicity, or any 
criterion for stopping the study drug or withdrawal from the trial occurs. Tumor 
assessments will be conducted every 6 weeks from first dose until disease progression 
or a new line of therapy is initiated. 
End-of-Treatment (Phase 1 and Phase 2) 
Discontinuation Visit and Safety Follow-up Visit: 
All subjects who discontinue the trial treatment prematurely for an AE should have a 
full safety evaluation at the time of discontinuation (Discontinuation Visit).  
A mandatory Safety Follow-up Visit should be scheduled 4 weeks after the last dose of 
study drug or before the initiation of a new antineoplastic treatment, whichever comes 
first. Subjects with an AE of Grade > 1 will be further followed until the resolution of 
the AE to Grade 0-1 or until beginning of a new antineoplastic therapy, whichever 
occurs first. Subjects with an adverse drug reaction (ADR) ongoing at the Safety 
Follow-up Visit must be followed up until the ADR resolves, becomes stable, or is 
considered not clinically significant by the Investigator. 
Follow-up Phase (Phase 1 and Phase 2) 
Subjects who discontinue treatment will be followed for up to 12 months (Phase 1) or 
24 months (Phase 2) after the last dose of study drug or until death, withdrawal of 
consent, or becoming lost to follow-up.  
Follow-up Visits 
Visits with associated evaluations and procedures will occur every 3 months for up to 
12 months following the last dose of study drug or until disease progression and/or start 
of a new line of therapy. Tumor assessments will continue every 6 weeks from first dose 
until discontinuation of study drug. 
Survival Follow-up (Phase 2 only) 
Subjects in Phase 2 who present with progressive disease and/or start a new line of 
therapy will be contacted by phone every 2 months to assess for survival for up to 
12 months after the last dose of study drug. 
Statistical 
Considerations: 
The total sample size is expected to be approximately 200 subjects: 50 in Phase 1 and 
150 in Phase 2.  
All data recorded will be presented in individual listings and, where appropriate, 
summarized in a descriptive manner. Continuous variables may be summarized using 
mean, standard deviation, median, and range; categorical variables will be summarized 
using counts and percentages. 
Phase 1: 
The sample size of approximately 50 subjects was determined by clinical 
considerations. 

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Phase 2: 
The primary endpoint of Phase 2, ORR, will be estimated as the binomial proportion of 
patients with confirmed partial or complete best overall response per RECIST 1.1, as 
determined by an IERC, and will be reported with two-sided, 95% Wilson score 
confidence interval (CI).  
With 150 patients in the final analysis, the power to exclude an ORR of 5% by the lower 
limit of the 95% two-sided Wilson score CI is 92.2% and 96.2%, assuming a true ORR 
of 12% and 13%, respectively. The sample size will provide ≥ 77% probability to observe 
an AE with and underlying rate of ≥ 1%. 
Interim analyses will be performed to assess the safety and efficacy (using the ORR and 
selected secondary efficacy endpoints) when (1) data are available for approximately 30 
subjects treated for at least 3 months and (2) approximately 3 months after approximately 
100 patients are dosed. No early stopping for efficacy will be performed, as a more 
complete safety assessment and evaluation of durability of responses are necessary for 
determination of risks and benefits. Consequently, the interim analyses will not affect the 
overall type I error. A non-binding futility analysis may be performed using methods 
described in the statistical analysis plan. Additional interim analyses for safety and 
efficacy assessment may performed. 
Statistics for continuous variables may include means, medians, ranges, and appropriate 
measures of variability. Statistics for the binary endpoint will be summarized with 
counts and frequencies, and statistics for time-to-event data will be summarized with 
median, 95% CI, etc., as appropriate.  
 
 

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1. 
INTRODUCTION AND RATIONALE 
In the past 2 decades, researchers have demonstrated the importance of the immune system in 
controlling cancer. Advances in our understanding of immuno-oncology have highlighted the 
dynamic interplay between host and tumor, and have shown that a tumor’s ability to evade the 
immune system can determine outcome. This has led to the development of therapies that are 
changing the landscape of modern oncology. Researchers have dissected numerous regulatory 
pathways that are exploited by cancer to evade immune response.  
The programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 
(CTLA-4) proteins are the most extensively studied negative regulatory receptors, and whose 
pathways are the target of multiple therapies (Buchbinder & Desai 2016; 
Sharma & Allison 2015; Topalian et al 2015). Inhibition of the PD-1 and CTLA-4 pathways by 
blockade of receptor-ligand interactions has been demonstrated in numerous clinical trials to 
result in objective clinical response and increased survival in several solid tumor indications. 
These studies have led to a number of regulatory approvals across the globe for single agents and 
combinations in various indications including melanoma, non-small cell lung cancer (NSCLC), 
renal cell carcinoma, head and neck cancers, Hodgkin lymphoma, and micro-satellite 
instability-high (MSIHI) cancers. This protocol will study the PD-1 antibody, AGEN2034. 
The first subject enrolled in this trial in early 2017. At the time this amendment was finalized, 
while enrollment for Phase 1 was completed, some subjects were still participating in Parts A1 
and A2. This amendment focuses primarily on changes to Phase 2 of this trial.  
1.1. 
PD-1 Checkpoint Blockade 
1.1.1. 
PD-1 Pathway Blockade 
The importance of immune surveillance in controlling outgrowth of neoplastic transformation is 
well described and consistent with a correlation between prevalence of tumor-infiltrating 
lymphocytes in cancer tissues and favorable prognosis in various malignancies (Disis 2010). 
Tumors can nevertheless evade recognition and destruction by the immune system by expressing 
soluble and cell-expressed molecules that naturally mediate immune suppression 
(Topalian et al 2015). In this context, the PD-1 checkpoint inhibitor pathway has emerged as a 
significant mode by which tumors suppress immune control (Postow et al 2015). 
PD-1, or CD279, is a member of the immunoglobulin superfamily (IgSF) that negatively 
regulates T-cell responses to maintain peripheral tolerance and immune homeostasis 
(Zha et al 2004). A range of T-cell subsets, including activated T effector cells, memory T cells, 
regulatory T cells, and T follicular helper cells, express PD-1. PD-1 is rapidly upregulated on T 
cells activated via their T-cell receptor (TCR). Under conditions of persistent antigenic exposure, 
such as in chronic pathogenic infections or within the tumor microenvironment, PD-1 expression 
can be sustained on antigen-specific T cells, leading to a state of dysfunction commonly referred 
to as T-cell exhaustion (Barber et al 2006). 
PD-1 signaling is mediated by 2 ligands: PD-1 ligand 1 (PD-L1 or CD274) and PD-1 ligand 2 
(PD- L2 or CD273) (Latchman et al 2001). PD-L1 is expressed on the cell surface of a range of 
immune and non-immune cell types, including antigen-presenting cells (APCs) and tumor cells. 
Upon binding to PD-L1 or PD-L2, PD-1 signaling in T cells can potently attenuate TCR 

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signaling, resulting in diminished cytokine and proliferative responses, reduced T effector cell 
cytolytic activity, and impaired central memory T-cell differentiation (Allie et al 2011). Proximal 
to ligand binding, PD-1 recruits Src homology region 2 domain–containing phosphatase (SHP)–1 
and SHP-2 proteins to an immunoreceptor tyrosine-based inhibitory motif and an 
immunoreceptor tyrosine-based switch motif within its intracellular domain (Chemnitz et al 
2004). This impairs phosphorylation of several key kinase proteins, including zeta chain–
associated protein kinase 70, phosphatidylinositol 3-kinase, protein kinase B, casein kinase 2, 
and protein kinase C theta, thereby attenuating signaling through these gene regulatory pathways 
(Yokosuka et al 2012). 
Inhibition of the PD-1 pathway by blockade of receptor-ligand interactions has been 
demonstrated to improve clinical outcome in a range of malignancies. The therapeutic benefit of 
such a blockade in the treatment of subjects with cervical cancer is under investigation. 
1.1.2. 
AGEN2034 
AGEN2034 is a novel, fully human monoclonal immunoglobulin G4 (IgG4) antibody, designed 
to block PD-1 from interacting with its ligand PD-L1 and PD-L2 in a manner comparable to 
nivolumab. 
1.1.2.1. 
Summary of Preclinical Data 
The utility of PD-1 as a therapeutic antibody target in human cancer has been well characterized. 
A human immunoglobulin G4 antibody with immunoglobulin kappa light chains (IgG4κ) 
monoclonal antibody directed against PD-1 (nivolumab, Opdivo®) has been evaluated in 
thousands of patients covering a range of IV doses, from 0.1 mg/kg to 20 mg/kg 
(Topalian et al, 2015). AGEN2034 is physicochemically comparable to nivolumab (anti-PD-1 
specific IgG4 antibodies with Igκ light chains) and a side-by-side in vitro pharmacological 
characterization of AGEN2034 and nivolumab demonstrated that these two antibodies were 
functionally comparable. More specifically both antibodies: 1) bind human PD-1 with 
subnanomolar affinities (KD 0.14 nM for AGEN2034 and 0.12 nM for nivolumab) and have 
comparable relative cellular binding affinities to human T cells expressing PD-1 (EC50 
0.025 µg/mL for AGEN2034 and 0.03 µg/mL for nivolumab) (Figure 1A); 2) potently block the 
binding of PD-L1 to PD-1 (IC50 0.03 µg/mL for both antibodies) (Figure 1B); and 3) augment 
the activation of recombinant PD-1 expressing and primary human T cells (Figure 1C-D). 
AGEN2034 toxicity was assessed in a 4-week good laboratory practices (GLP) repeat dose study 
in cynomolgus monkeys and in a human tissue cross reactivity study. Details of these studies can 
be found in the Investigator’s Brochure. Briefly, in the 4-week GLP repeat dose study, 
AGEN2034 was dosed by IV bolus administration of 0 (vehicle), 40 and 300 mg/kg on Study 
Days 1, 8, 15, 22 and 29, to 3 male and 3 female animals in the control and low dose groups and 
5 male and 5 female animals in the high dose group. The dosing period was followed by a 
4-week non-dosing period for 2 males and 2 females each in the vehicle and 300 mg/kg dose 
groups. Standard study endpoints, plus electrocardiogram (ECG), ophthalmic, and cardiovascular 
assessments, were included. 

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Figure 1: In vitro Comparability of AGEN2034 and Nivolumab 
 
Head-to-head evaluation of AGEN2034 (black), commercial nivolumab (gray), or IgG4 isotype antibody (white) 
for: (A) - antibody binding to PD-1+ CD4+ T cells in cultures of Staphylococcus enterotoxin A (SEA)-stimulated 
human peripheral blood mononuclear cells (PBMCs); (B) - antibody-mediated blockade for PD-1 binding to PD-L1; 
(C) - inhibition of PD-1:PD-L1 signaling in a T-cell reporter assay; and (D) - T cell–induced IL-2 release in SEA-
stimulated PBMC cultures. On the x-axis, log converted antibody concentration (log µg/mL) are shown. Data shown 
are representative of 2 independent experiments. 
 
In this study, AGEN2034 demonstrated biphasic distribution after IV bolus dose administration 
and serum AGEN2034 concentrations increased in a manner commensurate with the increase in 
dose. There were no apparent differences in the exposure or disposition of AGEN2034 between 
male and female monkeys. The estimated mean half-life was 12.4 days in the recovery phase, 
and it is anticipated that steady-state conditions might be achieved in about 5 to 9 weeks. Anti-
drug antibodies as a measure of immunogenicity of AGEN2034 in monkeys were assessed and 
revealed positive results at an incidence of 30 percent. Full toxicokinetic details are included in 
the AGEN2034 Investigator’s Brochure. 
The no-observed- adverse-effect level (NOAEL) of AGEN2034 from the 4-week cynomolgus 
monkey toxicity study is 40 mg/kg. Histopathology findings at 300 mg/kg included 
vascular/perivascular inflammation in a variety of tissues. The collective histology, IHC, PK and 
anti-drug antibody (ADA) data are consistent with an immune-mediated vasculitis caused by 
ADA formation in a proportion of monkeys given 300 mg/kg AGEN2034. ADA is a recognized 
phenomenon in non-human primate studies as it relates to the antigenicity of an administered 
humanized antibody and these types of events are typically not correlated with the formation of 
ADA in human patients (Frazier et al 2015; Ponce et al 2009; Rojko et al 2014). Other treatment-
related findings in the 4-week study were consistent with pharmacodynamic effects including 
changes in lymphoid cellularity in the spleen (increased at ≥ 40 mg/kg) and thymus (decreased at 
300 mg/kg) and an increase in mononuclear cell infiltration in the brain (≥ 40 mg/kg). These 
findings related to some changes in organ weights that showed a trend towards recovery 
following the 4-week non-dosing phase. Cytokine measurements from the 4-week toxicity study 

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in cynomolgus monkeys and from an in vitro cytokine release assay in human whole blood 
revealed no findings that are considered related to cytokine release syndrome. 
A human tissue cross-reactivity GLP study was completed using cryosections from a full panel 
of normal human adult tissues at two concentrations (15 and 30 µg/mL AGEN2034). 
AGEN2034- specific membrane and/or cytoplasmic staining was observed in cells of splenic 
white pulp and tonsillar germinal centers. This is consistent with the expected membrane staining 
pattern of PD-1 on a subset of T lymphocytes. 
For detailed information on preclinical characterization, manufacturing and administration of 
AGEN2034, please refer to the AGEN2034 Investigator’s Brochure. 
1.1.2.2. 
Summary of Clinical Data 
There are no existing safety data for AGEN2034, as this study will support its first human 
administration. 
The best indication of the safety profile of AGEN2034 is expected to be the safety profile of 
nivolumab (Opdivo®), as specified in its prescribing information (Opdivo® 2017). 
Per Amendment 4, this study would further support safety and efficacy data utilizing the 
expansion cohort of subjects with cervical cancer. 
1.1.3. 
Safety of Nivolumab 
The following safety information is based on data from 7 clinical trials in which 2,166 subjects 
received nivolumab as a single agent for treatment of unresectable or metastatic melanoma, 
metastatic NSCLC, advanced renal cell carcinoma (RCC), and classical Hodgkin’s lymphoma 
(cHL). Across all trials, nivolumab treatment was discontinued in 4% to 16% of subjects and 
delayed in 23% to 44% of subjects because of toxicities. Serious adverse reactions occurred in 
21% to 47% of subjects. Fatal adverse reactions were also observed. 
1.1.3.1. 
Common Adverse Reactions of Nivolumab 
Adverse reactions observed in more than 20% of subjects treated with nivolumab in clinical trials 
included (Opdivo® 2015): 
• In melanoma: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, and nausea. 
• In metastatic NSCLC: Fatigue, musculoskeletal pain, decreased appetite, cough, and 
constipation. 
• In advanced RCC: Asthenic conditions (decreased activity, fatigue, and malaise), 
cough, nausea, rash, dyspnea, diarrhea, constipation, decreased appetite, back pain, 
and arthralgia. 
• In cHL: Fatigue, upper respiratory tract infection, pyrexia, diarrhea, and cough. 
The most frequent severe or serious reactions, occurring in more than 2% of patients, included: 
• In melanoma: 
− Pretreated (n = 268): 2%–5% abdominal pain, hyponatremia, increased aspartate 
aminotransferase, and increased lipase. 

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− Untreated (n = 206): 2%–4% gamma-glutamyl transferase (GGT) increase, 
diarrhea, musculoskeletal pain, increased alanine aminotransferase (ALT), 
increased aspartate aminotransferase (AST), increased alkaline phosphatase, and 
increased bilirubin. 
− Nivolumab-only arm of combination study (n = 313): 2%–5% diarrhea, increased 
ALT, increased AST, hyponatremia, increased alkaline phosphatase, anemia, and 
lymphopenia (4.3%); and increased lipase (9%). 
• In NSCLC (n = 287): >2% serious pneumonia, pulmonary embolism, dyspnea, 
pleural effusion, and respiratory failure. 
• In RCC (n = 287): >2% serious acute kidney injury, pleural effusion, pneumonia, 
diarrhea, and hypercalcemia. 
• In cHL (n = 263): >1% serious infusion-related reaction, pneumonia, pleural effusion, 
pyrexia, rash, and pneumonitis. 
1.1.3.2. 
Notable Immune-Mediated Adverse Reactions of Nivolumab 
Immune-mediated conditions are defined as adverse reactions requiring the use of 
corticosteroids, with no clear alternate etiology. The most common immune-mediated reactions 
associated with nivolumab include pneumonitis (including interstitial lung disease), colitis, 
hepatitis, encephalitis, nephritis and/or renal dysfunction, rash, and endocrinopathies such as 
hypophysitis, adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus. The majority 
of events were moderate or mild; however, severe events were observed, including fatal cases of 
pneumonitis, fatal limbic encephalitis, and toxic epidermal necrolysis. The onset time of these 
events is highly variable, ranging from within 1 to 2 days of first dose to more than 2 years after 
initiation of therapy. In many cases, the events resolved with corticosteroid treatment, and 
occasional event recurrence was observed after re-initiation of nivolumab therapy. 
In fewer than 1% of patients, the following clinically significant immune-mediated adverse 
reactions occurred: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, 
polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, 
systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, motor dysfunction, 
vasculitis, and myasthenic syndrome. 
1.2. 
Rationale for Dose Selection 
1.2.1. 
Starting Dose in Phase 1 
The NOAEL of AGEN2034 from the 4-week cynomolgus monkey toxicity study was 40 mg/kg 
(see Section 1.1.2.1). This dose and serum AGEN2034 concentrations were used in the 
calculations below for the safe starting dose. 
For the clinical trial, the starting dose of 1 mg/kg was selected based on the results of 
2 complementary approaches: 
• Nonclinical safety: human equivalent dose (HED) projections based on the NOAEL 
of 40 mg/kg from the 4-week GLP toxicity study in cynomolgus monkey 

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• Biological effects and efficacy: AGEN2034 is biologically active in several in vitro 
assays, including: 1) inhibition of PD-1 binding to PD-L1/PD-L2; 2) promotion of 
TCR signaling in a T cell–based reporter gene assay; 3) increase of T-cell IL-2 
production; and 4) increase in T-cell proliferation under conditions of immune 
suppression. 
Two regulatory guidelines can be used for determination of the human starting dose of 
AGEN2034, starting from the NOAEL: 
• International Council for Harmonisation (ICH) S9 “Nonclinical Evaluation for 
Anticancer Pharmaceuticals” (Food and Drug Administration 2010) provides 
2 methods to determine a safe starting dose: 
− HED based on average serum AGEN2034 concentrations from the cynomolgus 
monkey study and a 10x safety factor are derived per the guidance in Section IIIA 
of ICH S9. 
− The highest non-severely toxic dose (HNSTD) in mg/kg from non-rodent studies 
and a 6x safety factor are derived from Section V, Note 2 of ICH S9. 
• In addition, the maximum recommended starting dose (MRSD), the HED based on 
the NOAEL dose and a 10x safety factor, is derived from the United States Food and 
Drug Administration (FDA) Guidance for Industry “Estimating the Maximum Safe 
Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers” 
(Food and Drug Administration Center for Drug Evaluation and Research 2005). 
• An additional 2-fold safety factor is included in each calculation to conservatively 
compensate for the observed < 2-fold difference of cellular binding affinity to human 
PD-1 as compared to cynomolgus monkey PD-1. 
 
Table 1: AGEN2034 Starting Dose Calculations 
AGEN2034 Dose From 4-Week 
Cynomolgus Monkey Study(1) 
HED 
(ICH S9 IIIA)(2) 
HNSTD  
(ICH S9 V Note 2)(3) 
MRSD 
(FDA VC3)(4) 
40 mg/kg (NOAEL) 
0.9 mg/kg 
3.3 mg/kg 
2.0 mg/kg 
300 mg/kg 
8 mg/kg 
25 mg/kg 
15 mg/kg 
Abbreviations: FDA: Food and Drug Administration; HED: human equivalent dose; HNSTD: highest non-severely 
toxic dose; ICH: International Council for Harmonisation; MRSD: maximum recommended starting dose; NOAEL: 
no-observed-adverse-effect level. 
1 All calculations include an additional 2-fold safety factor to conservatively compensate for binding affinity 
difference. 
2 Based on cynomolgus monkey AGEN2034 Cavg: 40 mg/kg Cavg = 488 μg/mL; HED calculation using a 2,500 mL 
human blood volume and 70 kg human body weight. 
3 Based on an HNSTD value calculated as 1/6 of the mg/kg dose. 
4 Food and Drug Administration, Center for Drug Evaluation and Research, 2005. 
 
Collectively, these guidance documents indicate a safe clinical starting dose within the 1 to 
3 mg/kg range based on the NOAEL of 40 mg/kg. If the 300 mg/kg dose is considered 

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appropriate for human safe dose calculations, this would provide an even greater level of safety 
cover, between 8 to 25 mg/kg, for a clinical starting dose. 
There is no cross-species reactivity to rodent PD-1 to warrant conducting rodent in vivo studies, 
although in vitro human data have demonstrated that AGEN2034 exhibits a pharmacological 
profile consistent with antagonism of the PD-1/PD-L1 interaction. These results indicate the 
estimated minimum anticipated biological effect level (MABEL) at EC10 is approximately 
7.3 x 10-4 mg/kg; at EC50 is 6.6 x 10-3 mg/kg; and at EC90 is 0.17 mg/kg. It is anticipated that 
administration of 1 mg/kg AGEN2034 every 2 weeks will result in blood AGEN2034 
concentrations that will exceed the EC90 throughout the duration of the administration cycle, 
which allows administration of an efficacious dose to subjects who are seriously ill. 
Furthermore, AGEN2034 and a marketed PD-1 inhibitor, nivolumab, have comparable efficacy 
profiles in a number of in vitro assays. Nivolumab, as well as another marketed PD-1 inhibitor, 
pembrolizumab, have shown clinical activity of this class and an overall acceptable safety 
profile, leading to regulatory approval for these drugs as a treatment of several malignancies. 
In conclusion, the proposed safe starting dose of AGEN2034 is 1 mg/kg administered every 
2 weeks to subjects with advanced malignancies who have progressed after standard treatment 
and for which no established therapy is available. 
1.2.2. 
Dose in Phase 2 
The choice of the Phase 2 dose was based on clinical data from the Phase 1 portion of this trial, 
evaluating AGEN2034 as monotherapy. Supportive clinical responses are also available from 
publications of similar-mechanism competitor nivolumab (anti PD-1; Opdivo®) as monotherapy 
since AGEN2034 has been shown to be functionally comparable to nivolumab. 
Dosing for Phase 1 was guided by preclinical pharmacokinetics (PK), preclinical pharmacology, 
and comparisons to published results of nivolumab as monotherapy. 
In Phase 1, a partial response was reported (Drescher et al 2018) in the 3 mg/kg every 2 weeks 
(q2wk) cohort that later was designated a complete response. Preliminary PK analysis of Phase 1 
data suggests an AGEN2034 terminal half-life of approximately 10 days. Therefore, dosing 
AGEN2034 q2wk results in only a 25% increase in accumulation ratio compared to every 
3 weeks. AGEN2034 dosed at 3 and 10 mg/kg q2wk resulted in average plasma AGEN2034 
concentrations (Cavg) of 20 and 67 µg/mL, respectively (corresponding to 1.30 and 1.80 µg/mL 
when log-transformed). When these log-transformed values are compared with receptor 
occupancy and IL-2 AGEN2034 concentration-response profiles, the AGEN2034 Cavg values are 
clearly on the flat saturated part of the dose-response curves for these key pharmacodynamic 
parameters. Therefore, no additional benefit is expected for AGEN2034 doses greater than 
3 mg/kg q2wk. 
Since limited clinical efficacy information is available from the ongoing evaluations, the primary 
decisions for the recommended Phase 2 dose (RP2D) of AGEN2034 were based on (1) the 
complete response experienced with the 3 mg/kg q2wk dose in Phase 1, and (2) favorable 
comparison of attained clinical Cavg to key preclinical pharmacodynamic evaluations. Therefore, 
3 mg/kg q2wk was the dose and regimen selected as RP2D for evaluation in Phase 2 of this trial. 

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1.3. 
Rationale for Expansion Cohort 
Subjects with unresectable or metastatic cervical cancer with disease progression after a 
platinum-based treatment regimen will be enrolled in an expansion cohort. This population has a 
high unmet need for effective therapy, and there is a strong rationale for the use of a PD-1 
therapeutic antibody. 
It is estimated that 12,800 new cases of cervical cancer will be diagnosed in the US in 2017, with 
4,200 deaths attributable to this malignancy (Siegel et al 2017). More widely, cervical cancer is 
the 4th most common cause of cancer death for women worldwide (Torre et al 2015). Human 
papilloma virus (HPV) vaccination is expected to reduce the incidence of cervical cancer over 
time, however vaccination rates in female adolescents remain below 50% in many parts of the 
US (Reagan-Steiner et al 2016) and unresectable or metastatic disease is likely to remain an 
important health concern. The current standard of care for the first-line treatment of recurrent or 
metastatic cervical cancer is platinum doublet chemotherapy with or without bevacizumab 
(National Comprehensive Cancer Network 2016; Tewari et al 2014). While a number of agents 
may be utilized in clinical practice for the second-line treatment of cervical cancer currently, 
none can be regarded as definitive with proven survival benefit; therefore, clinical trials are often 
recommended for such individuals (Borcoman & Le Tourneau 2017). 
The use of checkpoint protein blockade in the treatment of cervical cancer is supported by 
observations of high PD-L1 expression in cancers with viral etiology, including cervical cancer 
(Schumacher & Schreiber 2015; Mezache et al 2015). The upregulation of PD-1 and PD-L1 was 
also shown to correlate with impaired immunity in high-risk HPV-related cervical cancer 
(Yang et al 2013). Furthermore, initial trials of PD-1 therapeutic antibodies have demonstrated 
activity in this disease. In the KEYNOTE-028 study 24 subjects with unresectable or metastatic 
PD-L1 positive cervical cancer, who had failed first-line therapy, received pembrolizumab at a 
dose of 10 mg/kg IV every 2 weeks. Four subjects (17%) had a Response Evaluation Criteria in 
Solid Tumors version 1.1 (RECIST 1.1) partial response with a median duration of response of 
26 weeks (Frenel et al 2016). The safety profile of pembrolizumab was consistent with that 
observed in trials in other tumor types. In the KEYNOTE-158 study, a similar group of subjects 
with cervical cancer received pembrolizumab at a dose of 200 mg once every 3 weeks until 
disease progression or 2 years. In this second study, 98 subjects have been treated regardless of 
PD-L1 biomarker status. The ORR in the PD-L1 positive cohort (81 subjects) was 16% including 
3 subjects with complete response. None of the 17 subjects with PD-L1 negative cancers 
responded. Again many of the responses were shown to be durable (Chung et al 2018). 
Pembrolizumab was approved by the US FDA in June 2018 for patients with recurrent or 
metastatic cervical cancer with disease progression on or after chemotherapy whose tumors 
express PD-L1 (CPS ≥ 1) as determined by an FDA-approved test (Food and Drug 
Administration 2018). Finally, nivolumab has been studied in a trial of subjects with virus-
associated cancers including 19 subjects with cervical cancer. Nivolumab was given at a dose of 
240 mg every 2 weeks. Subjects were required to have had 2 or fewer prior treatment regimens 
for advanced disease and were unselected for PD- L1 expression. One subject had a complete 
response and 4 subjects had partial response for an overall response rate of 26%. In the study 
population as a whole the response rate was higher in HPV positive cancers (28.6%) than in 
cancers with unknown HPV status (10.0%) (Hollebecque et al 2017). These findings of clinical 

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activity with durable responses support the study of AGEN2034 in subjects with unresectable or 
metastatic cervical cancer with disease progression after standard first-line therapy. 
1.4. 
Rationale for Biomarker Assessment  
1.4.1. 
Biomarkers in Phase 1 
When the study started, due to limited understanding of the biological activities induced by 
AGEN2034 in cancer subjects, there was no certainty that the doses examined will be associated 
with relevant antitumor immune activities. As a consequence, the study will serve to: evaluate 
receptor occupancy at different dose levels; investigate the mechanism of action of the drug by 
monitoring immune cell subset activation status; and evaluate potential predictive/prognostic 
biomarker candidates related to the drug and/or cancer (e.g., level of PD-L1 tumor expression, 
HPV status). 
1.4.2. 
Biomarkers in Phase 2 
Phase 2 of the study will continue to investigate the mechanism of action of the drug by 
monitoring immune cell subset activation status; will monitor 
 
as a non-invasive reflection of the tumor burden; will evaluate potential predictive/prognostic 
biomarker candidates related to the drug and/or cancer (e.g., level of PD-L1 tumor expression, 
HPV status). 
1.4.3. 
Assessment of PD-L1 Expression in Tumors 
PD-L1 expression has been associated with response to PD-1. In treatment naive NSCLC, a 
PD-L1 expression level of ≥ 50% tumor proportion score (TPS) as a companion diagnostic for 
treatment with pembrolizumab was evaluated and is now approved. 
There is limited data available on PD-L1 expression in cervical cancer, particularly in subjects 
with metastatic disease who have relapsed after initial therapy. In a recent publication by Reddy 
et al (2017), 34% of subjects with cervical cancer were PD-L1 positive. On June 12, 2018, the 
US Food and Drug Administration approved pembrolizumab for patients with recurrent or 
metastatic cervical cancer with disease progression on or after chemotherapy whose tumors 
express PD-L1 (CPS ≥ 1) as determined by an FDA-approved test (Food and Drug 
Administration 2018). In KEYNOTE-158, 98 subjects have been treated regardless of PD-L1 
biomarker status. The response rate in the 81 PD-L1 positive cancers was 16% including 
3 subjects with complete response (Chung et al 2018). 
In this study, the hypothesis is that subjects with positive PD-L1 expression may have improved 
anti-tumor response, therefore tumor tissue is required for subjects in trial Phase 2. This is an 
exploratory biomarker that, in the future, may help to determine the patients who will best 
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2. 
OBJECTIVES, ENDPOINTS, AND BENEFIT/RISK 
2.1. 
Objectives and Endpoints  
The objectives and associated endpoints for Phase 1 and Phase 2 are shown in Section 2.1.1 and 
Section 2.1.2, respectively.  
2.1.1. 
Phase 1 
 
Objective 
Endpoint 
Primary 
• 
To assess the safety and tolerability 
of AGEN2034 in subjects with 
metastatic and/or locally advanced 
solid tumors 
• 
Occurrence of DLTs in subjects in dose 
escalation during the first 21 days of treatment 
• 
Frequency, severity, and duration of treatment-
emergent adverse events (TEAEs) and 
laboratory abnormalities using the National 
Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI CTCAE) v4.03. 
Secondary 
• 
To characterize the AGEN2034 
pharmacokinetic (PK) profile  
• 
AGEN2034 PK parameters which may include 
(but are not limited to) maximum drug 
concentration observed postdose at steady-state 
(Cmax-ss), minimum observed concentration at 
steady-state (Cmin-ss), area under the drug 
concentration-time curve within time span t1 to 
t2 at steady-state (AUC(t1-t2)-ss), area under the 
drug concentration-time curve from time zero to 
time t (AUC(0-t)), area under the drug 
concentration-time curve from time zero to 
infinity (AUC(0-∞)), time to maximum observed 
concentration (tmax), terminal disposition rate 
constant (λz), terminal elimination half-life (t1/2), 
systemic clearance (CL), and volume of 
distribution (Vd) 
 
• 
To correlate AGEN2034 exposure 
with target occupancy 
• 
Receptor occupancy on circulating T cells 
measured 4 hours after the 1st dose and 
immediately prior to the 2nd dose 
• 
Receptor occupancy saturation levels correlated 
with AGEN2034 PK exposure metrics 
 
• 
To evaluate the immunogenicity of 
AGEN2034 and correlate it to 
exposure 
• 
Antidrug antibody (ADA) concentrations and 
correlation with AGEN2034 PK exposure 
metrics 
Exploratory 
 
• 
To explore the association of 
programmed cell death protein 1 – 
ligand 1 (PD-L1) expression with 
clinical responses 
• 
Baseline expression of PD-L1  
 
 
 

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2.1.2. 
Phase 2 
 
Objective 
Endpoint 
Primary 
• To assess objective response rate 
(ORR) according to RECIST 1.1 as 
determined by an Independent Endpoint 
Review Committee (IERC) 
• Confirmed ORR per RECIST 1.1, as determined 
by an IERC, in the analysis population 
Secondary 
• To assess the safety and tolerability of 
AGEN2034 in subjects with metastatic 
and/or locally advanced solid tumors 
• Frequency, severity, and duration of TEAEs and 
laboratory abnormalities, using NCI CTCAE 
v4.03. 
 
• To characterize the AGEN2034 PK 
profile 
• AGEN2034 PK parameters which may include 
(but are not limited to) maximum drug 
concentration observed postdose at steady-state 
(Cmax-ss), minimum observed concentration at 
steady-state (Cmin-ss), area under the drug 
concentration-time curve within time span t1 to 
t2 at steady-state (AUC(τ1-τ2)-ss), area under the 
drug concentration-time curve from time zero to 
time t (AUC(0-t)), area under the drug 
concentration-time curve from time zero to 
infinity (AUC(0-∞)), time to maximum observed 
concentration (tmax), terminal disposition rate 
constant (λz), terminal elimination half-life (t1/2), 
systemic clearance (CL), and volume of 
distribution (Vd) 
 
• To evaluate the immunogenicity of 
AGEN2034 and correlate it to exposure 
• ADA concentrations and correlation with 
AGEN2034 PK exposure metrics 
 
• To assess objective response rate 
(ORR) according to RECIST 1.1 as 
determined by investigator 
• Confirmed ORR per RECIST 1.1, as determined 
by an investigator 
 
• To assess duration of response (DOR), 
disease control rate (DCR), duration of 
stable disease (SD), time to response, 
and progression-free survival (PFS) 
time per RECIST 1.1 
• DOR per RECIST 1.1, as determined by an IERC 
and investigator, defined as time from first 
observation of response to first observation of 
documented disease progression (or death within 
12 weeks after last tumor assessment). Subjects 
without an event at analysis cutoff date will be 
censored on date of last tumor assessment. 
• DCR, defined as proportion of subjects with 
complete response (CR), partial response (PR), or 
stable disease (SD) for at least 12 weeks 
• Duration of SD, measured from the start of 
treatment until the criteria for progression are 
met, taking as reference the smallest 
measurements recorded since the treatment 
started, including baseline measurements. 
• Time to response, defined as the time from the 
first dose date to first observation of confirmed 
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Objective 
Endpoint 
Secondary 
(continued) 
 
• PFS time, defined as time from first treatment 
administration to first observation of documented 
disease progression (or death within 12 weeks 
after last tumor assessment), per RECIST 1.1, as 
determined by an IERC and investigator. 
Subjects without an event at analysis cutoff date 
will be censored on date of last tumor 
assessment. 
 
• To assess overall survival (OS) rate  
• Median OS and OS rate 
 
• To assess OS time 
• OS time, defined as time from start of treatment 
to death. For subjects who are still alive at time 
of data cutoff for trial analysis or who are lost to 
follow-up, survival will be censored at the last 
recorded date that the subject is known to be 
alive as of the cutoff date for analysis 
Exploratory 
 
• To explore the association of 
programmed cell death protein 1 – 
ligand 1 (PD-L1) expression with 
clinical outcomes 
• Baseline expression of PD-L1 association with 
clinical outcomes 
 
2.2. 
Overall Risk/Benefit Assessment 
The risk-benefit relationship has been carefully considered in the planning of this trial. Based on 
preclinical and clinical data available to date, the conduct of the trial is considered safe and 
reasonable using the dose and schedule of AGEN2034 as specified for Phase 1, Cohort 1 in this 
clinical trial protocol.  
A Safety Monitoring Committee (SMC) in Phase 1 and an Independent Data Monitoring 
Committee (IDMC) in Phase 2 are planned for ongoing assessment of the risk-benefit ratio. The 
trial shall be discontinued in the event of any new findings that indicate a relevant deterioration 
of the risk-benefit relationship and would render continuation of the trial unjustifiable. The risks 
of exposure to AGEN2034 include: 
• Infusion-related reactions. 
• Increase in immune-related adverse events (irAEs), which constitute a unique 
spectrum of AEs that occur via activation of the subject’s immune system and that 
can sometimes lead to serious and even fatal events (Boutros et al 2016; 
Kumar et al 2017; Weber et al 2012). 
Infusion-related reactions are a risk inherent to administration of any recombinant protein to 
humans. The incidence of immunogenicity and the character or severity of immunogenicity- 
induced side effects cannot be predicted by animal models because humanized or fully human 
proteins usually provoke a much stronger immune-response in rodents or non-human primates 

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than in humans. However, for AGEN2034, clinical signs of hypersensitivity were not observed 
in pilot 4-week IV repeat-dose toxicity studies conducted in cynomolgus monkeys (a primate 
species closer to human). There were also no findings in an in vitro cytokine release assay in 
human whole blood. 
Immune-related AEs are events that are drug-related and can be explained by an immune 
phenomenon after other etiologies have been ruled out. Relevant clinical safety experience has 
been generated with several PD-1 pathway–blocking monoclonal antibodies and with the 
combination with CTLA-4 agents (Ott et al 2017; Boutros et al 2016; Kumar et al 2017). 
For the reasons noted previously, it is anticipated that the safety profile of nivolumab will 
provide a good estimate for the safety and tolerability of AGEN2034. Overall, the safety profile 
for nivolumab, which blocks the PD-1/PD-L1 axis at the same level as does AGEN2034, is 
acceptable in the context of treatment of subjects with advanced malignancies. Nevertheless, 
occurrence of AEs, especially irAEs, will be carefully monitored. 
A direct benefit is usually considered unlikely for participants in a Phase 1 trial, and that holds 
true for the current trial. However, even at the lowest dose, it is expected that the drug will be 
pharmacologically active, leading to blockade of PD-1 for at least part of the 14 days between 
each administration. 
The Phase 2 portion of the study will explore the activity of the selected AGEN2034 dose in the 
treatment of subjects with metastatic or locally advanced, unresectable cervical cancer who have 
relapsed after a platinum-based treatment regimen. There is no regimen with proven clinical 
benefit currently available to these subjects and the treatment with PD-1 blockade provides an 
opportunity to improve on the response rates observed with chemotherapy. 
Overall, the risk-benefit ratio of the proposed treatment with AGEN2034 is considered positive, 
and to further manage the potential for added risk, in this trial there will be pro-active monitoring 
for immunogenicity and pro-active management of immune related AEs. 
3. 
INVESTIGATIONAL PLAN 
This is a 2-part trial: a Phase 1, open-label, dose-escalation trial in subjects with metastatic or 
locally advanced solid tumors, with a consecutive Phase 2 expansion to evaluate efficacy in 
subjects with recurrent, unresectable, or metastatic (advanced) cervical cancer that has 
progressed after a platinum-based treatment regimen. 
3.1. 
Phase 1 (Part A): Dose Escalation 
Phase 1 (Part A) of the study will consist of a standard 3+3 dose escalation with the following 
escalating dose levels and schedules: 
• Part A1: 1, 3, and 10 mg/kg administered every 2 weeks 
• Part A2: 6 and 10 mg/kg administered every 3 weeks 
In Part A1, the first subject of each cohort will be observed for 16 days (i.e., ≥ 48 hours after 
second dose) for occurrence of dose-limiting toxicity (DLT) before the second subject is 
administered trial medication. Thereafter, within each cohort in the dose escalation phase of 
Part A1, consecutively enrolled subjects may initiate treatment ≥ 48 hours after the prior enrolled 

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subject initiated treatment. Dose escalation will continue until the MTD is reached or the 
maximum planned dose level (10.0 mg/kg) is shown to be safe. The MTD is defined as the dose 
below which ≥ 2 DLTs are observed. 
Once Part A1 is completed, enrollment for Part A2 will begin: 
• If < 2 DLTs are observed in dose escalation at the 10 mg/kg every 2 weeks dose level 
in Part A1, open enrollment will begin for Part A2 at the 6 mg/kg every 3 weeks dose 
level; enrollment of these subjects does not to have to be sequential (that is, a wait of 
48 hours between 2 subjects is not required). Once 10 subjects at the 6 mg/kg dose 
level have completed, open enrollment will begin for Part A2 at the 10 mg/kg every 
3 weeks dose level; enrollment of these subjects does not to have to be sequential 
(that is, a wait of 48 hours between 2 subjects is not required). 
• If ≥ 2 DLTs are observed in dose escalation at the 10 mg/kg every 2 weeks dose level 
in Part A1, standard 3 + 3 dose escalation will continue with Part A2. Within each 
dose level cohort, consecutively enrolled subjects may initiate treatment ≥ 48 hours 
after the prior enrolled subject initiated treatment. Dose escalation will continue until 
the MTD is reached or the maximum planned dose level for Part A2 (10.0 mg/kg 
every 3 weeks) is shown to be safe. 
Each subject will stay on the dose level and schedule assigned at trial entry. Subjects will receive 
AGEN2034 for a maximum of 24 months or until disease progression, unacceptable toxicity, or 
any criterion for stopping the study drug or withdrawal from the trial occurs. 
The DLT observation period for the dose escalation portion of Phase 1 (Parts A1 and A2) is the 
first 21 days following administration of AGEN2034. Subjects who do not complete the DLT 
evaluation period for reasons other than a DLT will be replaced. The decision to escalate to the 
next cohort will be made by the SMC, based on safety assessments after all subjects of a cohort 
have reached the end of the DLT evaluation period. See Section 9.1 for a description of the 
SMC. 
The dose escalation criteria are as follows: 
• For each dose level, DLTs are assessed during the first 21 days. The criteria for 
moving from one dose level to another do not allow escalation to the next cohort in 
cases in which ≥ 1 of 3 or ≥ 2 of 6 subjects in a dose-level cohort experience DLT. 
• If 1 of 3 subjects in a cohort experiences a DLT, this cohort will be expanded to 
6 subjects. 
• The MTD is defined as the highest dose at which < 2 of 6 subjects experience a DLT. 
Thus, the MTD cohort should accrue a total of ≥ 6 subjects. 
A schematic of dose escalation is presented in Figure 2. 
 
 

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Figure 2: Phase 1 Dose Escalation Schematic 
 
 
 
 
 
DLT: dose limiting toxicity; MTD: maximum tolerated dose 
 
It is conceptually acceptable to de-escalate to an intermediate, not pre-defined and not 
previously- studied dose level, if evaluation of toxicity at such a dose is desired. If this approach 
is taken, 3 new subjects should be enrolled at the new intermediate dose, and the aforementioned 
rules should be used to determine further enrollment at this dose level. 
The decision to expand a cohort to 6 subjects, to de-escalate and/or to open enrollment to the 
Dose Expansion Phase will be made by the SMC based on safety assessments after subjects of a 
cohort in dose escalation have reached the end of the DLT evaluation period. 
3.1.1. 
Dose-Limiting Toxicity 
In this trial, a DLT is defined as any treatment-related toxicity that is NCI CTCAE Grade ≥ 3, 
confirmed by the SMC to be relevant for the study drug treatment, and that occurs during the 
first 3 weeks of AGEN2034 treatment in the dose escalation portion of the trial (DLT evaluation 
period) for all dose cohorts and for all subjects with data used for implementing the dose-
escalation algorithm for determination of MTD. Additional subjects enrolled in the dose 
escalation phase will have AEs collected but will not have a specific DLT observation period. 
The SMC recognizes that in the absence of prior human experience with AGEN2034, a 
conservative approach will need to be adopted in ascribing the relevance of treatment-related 
toxicity to drug. Treatment-related serious adverse events (SAEs) will be ascribed as related to 
Starting Dose 
Treat 3 subjects,
Assess DLT after 3 weeks 
Escalate to next dose
level 
Determine
MTD 
MTD/maximum dose
to be confirmed on
total of 6 subjects 
Determine
MTD 
0 of 3 
Number 
of DLTs 
≥ 2 of 3 
No 
1 of 3 
Max 
dose per
protocol 
? 
Treat additional 3 subjects, 
Assess DLT after 3 weeks 
1 of 3 
Yes 
≤ 1 of 6 
Number 
of DLTs 
≥ 2 of 6 

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drug except where a clear relationship to the underlying disease or recognized co-morbidities is 
evident. 
Exceptions to this DLT definition include: 
• Grade 3 infusion-related reactions resolving within 6 hours and controlled with 
medical management. 
• Transient (≤ 6 hours) Grade 3 flu-like symptoms or fever, which are controlled with 
medical management. 
• Transient (≤ 24 hours) Grade 3 fatigue, local reactions, headache, nausea, or emesis 
that resolves to grade ≤ 1. 
• Grade 3 diarrhea, skin toxicity, or liver function test (ALT, AST, or GGT) increase 
that resolves to grade ≤ 1 in < 7 days after medical management (e.g., 
immunosuppressant treatment) has been initiated. 
• Single laboratory values out of normal range that are unlikely related to trial 
treatment according to the investigator, do not have any clinical correlate, and resolve 
to grade ≤ 1 within 7 days with adequate medical management. 
• Tumor flare phenomenon, defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor. 
Any DLT will immediately lead to permanent withdrawal of AGEN2034. 
3.1.2. 
Stopping Rules for Toxicity 
The SMC will meet to review any cohort under evaluation as well as the safety of all cohorts. 
Should > 33% subjects on any dose level experience toxicities that meet DLT criteria but occur 
after the DLT observation period or in subjects not included in the DLT analysis set, enrollment 
will be held and the occurrences will be thoroughly evaluated by the committee. The SMC will 
then make recommendations to re-open enrollment or to initiate other changes in study conduct 
(such as protocol amendments). 
If there is a subject death within 30 days after AGEN2034 administration for reasons not related 
to the subject’s disease progression, the trial will be put on hold to accrual and treatment held for 
subjects on study. The SMC will evaluate the cause of the event and recommend the appropriate 
change in study conduct. If the event is determined to be related to AGEN2034, then a study 
amendment and/or other corrective action plan will be established. If the event is determined not 
to be related to the AGEN2034, then the study will re-open to accrual and subjects on study will 
resume treatment. 
3.1.3. 
Backfill Expansion Enrollment for Each Dose Level Cohort in the Phase 1 
Concurrent with the 3+3 dose escalation schema, additional subjects will be backfilled to ensure 
that each combined dose level cohort enrolls at least 10 subjects: 
• Part A1: 
− Once the safety of the 1 mg/kg dose is established, enrollment for the 3 mg/kg 
dose cohort will begin. When accrual of first 3 subjects in the 3mg/kg cohort is 

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paused for the 21-day safety assessment and DLT observation, enrollment of 
≤ 7 subjects to backfill the 1 mg/kg cohort may begin. 
− When the safety of the 3 mg/kg dose has been established, enrollment for the 
10 mg/kg dose cohort will begin. When accrual for the 10 mg/kg dose cohort is 
paused for safety assessment and DLT observation, enrollment of ≤ 7 subjects to 
backfill the 3 mg/kg dose level can begin. 
Note: Enrollment of 10 subjects to the 1 mg/kg dose level must be completed 
before additional subjects can be enrolled to backfill the 3 mg/kg dose level. 
− When the safety of the 10 mg/kg dose has been established, ≤ 4 subjects may be 
enrolled at the same dose level, for a total of 10 subjects at 10 mg/kg. 
Note: Enrollment of 10 subjects to the 1 and 3 mg/kg dose levels must be 
completed before additional subjects can be enrolled to backfill the 10 mg/kg dose 
level. 
• Part A2: 
− Backfill for Part A2 will be considered if ≥ 2 DLTs are observed in dose 
escalation at the 10 mg/kg every 2-weeks dose level in Part A1 and dose 
escalation continues with Part A2. Backfill of Part A2 will proceed as follows: 
▪ 
When the safety of the 6 mg/kg dose has been established, enrollment for the 
10 mg/kg dose cohort will begin. When accrual for the 10 mg/kg dose cohort is 
paused for safety assessment and DLT observation, enrollment of ≤ 7 subjects to 
backfill the 6 mg/kg dose level can begin. 
▪ 
When the safety of the 10 mg/kg dose has been established, ≤ 4 subjects may be 
enrolled at the same dose level, for a total of 10 subjects at 10 mg/kg. 
Note: Enrollment of 10 subjects to the 6 mg/kg dose level must be completed 
before additional subjects can be enrolled to backfill the 10 mg/kg dose level. 
Backfill expansion enrollment of subjects for each cohort does not to have to be sequential (that 
is, a wait of 48 hours between 2 subjects is not required). Subjects enrolled to backfill each dose 
level cohort will have the purpose of generating additional safety, PK, and receptor occupancy 
data, and will not undergo formal DLT observation. 
3.2. 
Phase 2: Dose Expansion Phase 
There is no approved standard of care for second line treatment of advanced or metastatic 
cervical cancer. As such, these subjects would be eligible for the Phase 1 portion of the study; 
therefore, the SMC may decide to open enrollment to the expansion cohorts of this trial at a dose 
level that has been found to be safe and is expected to be active. 
The following expansion cohort will be enrolled: recurrent, unresectable, or metastatic cervical 
cancer.  
Enrollment of subjects for expansion cohort does not to have to be sequential (i.e., a wait of 
48 hours between 2 subjects is not required). Subjects will receive AGEN2034 for a maximum of 

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24 months or until disease progression, unacceptable toxicity, or any criterion for stopping the 
study drug or withdrawal from the trial occurs. 
The SMC will continue to evaluate safety on an ongoing basis for the Phase 2. Additionally, for 
the Phase 2 portion of the study, an IDMC will be established to evaluate safety and efficacy. 
3.3. 
Planned Number of Subjects 
3.3.1. 
Enrollment Targets 
The planned number of subjects for this trial is: 
• Phase 1 (Parts A1 and A2): approximately 50 subjects. 
• Phase 2: approximately 150 subjects with recurrent, unresectable and/or metastatic 
cervical cancer. 
The final sample size may vary depending on the total number of dose levels tested, and subject 
replacement for DLT evaluations. 
3.3.2. 
Subject Replacement Strategy 
In Phase 1, subjects who do not complete the DLT observation period defined in Section 3.1 for 
reasons other than a DLT may be replaced.  
In Phase 2, no subject will be replaced. 
3.4. 
Planned Trial Duration 
The maximum trial duration for a subject is estimated to be up to approximately 49 months. This 
includes a screening period, a planned treatment period of up to approximately 24 months, and a 
follow-up period of up to 24 months after the last dose of study drug. 
The overall trial duration is expected to be approximately 63 months:  
• First subject in: Q2 2017 
• Last subject out (after follow-up): Q2 2022 
3.5. 
Definition of End of Trial 
If the trial is not terminated for a reason provided in Section 4.4.3, the end of the trial is defined 
as 24 months after the last subject has received the last planned dose of study drug. 
3.6. 
Medical Care of Subjects After End of Trial 
At the end of the protocol-specified periods of active study therapy, the Sponsor will not 
continue to supply study drug to subjects/investigators unless the Sponsor chooses to extend the 
study. The investigator should ensure that the subject receives appropriate standard of care to 
treat the condition under study. 
Upon withdrawal from trial treatment, subjects may receive the care upon which they and their 
physicians agree. Subjects will be followed for survival and AEs as specified in Section 6. 

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4. 
SELECTION OF TRIAL POPULATION 
4.1. 
Target Population  
Phase 1 (Parts A1 and A2): 
Male and female subjects over the age of 18 years with metastatic or locally advanced solid 
tumors for which no standard therapy is available or standard therapy has failed. 
Phase 2:  
Female subjects over the age of 18 years with recurrent and/or metastatic cervical cancer who 
have relapsed after a platinum-based treatment regimen for advanced (recurrent, unresectable, or 
metastatic) disease. 
After the interim analyses, subsequent enrollment of subjects may be based on biomarker 
enrichment (including but not limited to PD-L1 expression). In such cases, tumor tissue must be 
positive for the selected entry biomarker prior to subject enrollment. 
4.2. 
Inclusion Criteria 
For inclusion in the trial, all of the following inclusion criteria must be fulfilled as no waivers 
will be permitted: 
1. Voluntarily agree to participate by giving written informed consent. Participation in 
pharmacogenomics testing is optional. 
2. Be ≥ 18 years of age. 
3. Diagnosis and prior systemic treatment: 
a. Phase 1: Have a histologically or cytologically confirmed diagnosis of a metastatic or 
locally advanced solid tumor for which no standard therapy is available or standard 
therapy has failed. 
b. Phase 2:  
I.  Have (1) a histologically or cytologically confirmed diagnosis of squamous-cell 
carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, and 
(2) metastatic, locally advanced, and/or unresectable disease at the time of 
enrollment. Histologic confirmation of the original primary tumor is required via 
pathology report. 
Note: The following cervical tumors are not eligible: minimal deviation/adenoma 
malignum, gastric type adenocarcinoma, clear cell carcinoma, and mesonephric 
carcinoma.  
II.  Has cervical cancer and has relapsed after a platinum-based treatment (first line) 
regimen for advanced (recurrent, unresectable, or metastatic) disease;  
 
Note: Subject receiving chemotherapy concurrently with primary radiation (e.g., 
weekly cisplatin) or subject receiving adjuvant chemotherapy following 
completion of radiation therapy (e.g., paclitaxel and carboplatin for ≤ 4 cycles) 
and progressed within 6 months after treatment completion will be eligible as this 
systemic therapy will be considered as first line treatment. 

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4. Measurable disease – based on investigator assessment 
a. Phase 1: Have objective evidence of disease; the presence of measurable disease is 
not required. 
b. Phase 2: Have measurable disease on imaging based on RECIST version 1.1. 
Note: Subjects must have at least one "target lesion" to be used to assess response, as 
defined by RECIST version 1.1. Tumors within a previously irradiated field will be 
designated as "non-target" lesions unless progression is documented or a biopsy is 
obtained to confirm persistence at least 90 days following completion of radiation 
therapy. 
Note: Measurable disease by RECIST 1.1 must be confirmed by independent central 
radiologic review prior to first dose. Subjects without centrally confirmed measurable 
disease at baseline will not be eligible for this trial. 
5. Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group 
(ECOG) performance status of 0 or 1. 
6. Have adequate organ function as indicated by the following laboratory values: 
a. Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.5 x 
109/L, platelet count ≥ 100 x 109/L, and stable hemoglobin ≥ 8 g/dL (without 
transfusions within 1 week before first dose). 
b. Adequate hepatic function based by a total bilirubin level ≤ 1.5 x the institutional 
upper limit of normal (IULN), aspartate aminotransferase (AST) level ≤ 2.5 x IULN, 
alanine aminotransferase (ALT) level ≤ 2.5 x IULN, and alkaline phosphatase ≤ 2.5 x 
IULN. 
c. Adequate renal function defined as creatinine ≤ 1.5 x IULN OR calculated creatinine 
clearance ≥ 50 mL/min for subjects with creatinine levels > 1.5 x IULN (if no local 
guideline is available, creatinine clearance should be calculated using the Cockcroft-
Gault Method). 
d. Adequate coagulation defined by international normalized ratio (INR) or prothrombin 
time ≤ 1.5 x IULN (unless the subject is receiving anticoagulant therapy); and 
activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless the subject is 
receiving anticoagulant therapy) 
7. Other than the cancer for which the subject is enrolled, have no history of prior 
malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder 
cancer, squamous-cell carcinoma of the skin, or has undergone potentially curative 
therapy with no evidence of that disease recurrence for 5 years since initiation of that 
therapy. 
8. In Phase 2, subjects must provide a sufficient and adequate formalin-fixed paraffin 
embedded (FFPE) tumor tissue sample preferably from the most recent biopsy of a tumor 
lesion, collected either at the time of or after the diagnosis of advanced or metastatic 
disease has been made AND from a site not previously irradiated. If no tumor tissue is 
available, a fresh biopsy will be required. (See Section 6.4.2.1 for details.) 
Note: Tissue from needle or excisional biopsy or from resection is required. 

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9. Female subjects must have a negative serum pregnancy test at screening (within 72 hours 
before first dose of study drug) if of childbearing potential or be of non-child bearing 
potential. Non-childbearing potential is defined as (by other than medical reasons): 
a. ≥ 45 years of age and has not menstruated for greater than 1 year, 
b. Amenorrheic for < 2 years without a hysterectomy and oophorectomy and a follicle-
stimulating hormone (FSH) value in the postmenopausal range upon pretrial 
(screening) evaluation, 
c. Whose status is post hysterectomy, oophorectomy or tubal ligation. 
10. If of childbearing potential, female subjects must be willing to use 2 highly effective 
methods (defined in the informed consent form [ICF]) throughout the study, starting with 
the screening visit through 120 days after the last dose of study drug. 
Note: Abstinence is acceptable if this is the established and preferred contraception for 
the subject. 
11. Male subjects with a female partner(s) of child-bearing potential must agree to use 
2 highly effective methods (defined in the ICF) throughout the trial starting with the 
screening visit through 120 days after the last dose of study drug is received. Males with 
pregnant partners must agree to use a condom; no additional method of contraception is 
required for the pregnant partner. 
Note: Abstinence is acceptable if this is the established and preferred contraception for 
the subject. 
12. Is willing and able to comply with the requirements of the protocol. 
4.3. 
Exclusion Criteria 
The subject must be excluded from participating in the trial if the subject: 
1. Is currently participating and receiving study therapy or has participated in a study of an 
investigational agent and received study therapy or used an investigation device within 
4 weeks before the first dose of treatment. 
2. Has an inadequate washout period prior to first dose of study drug defined as:  
a. Received systemic cytotoxic chemotherapy or biological therapy within 3 weeks 
before first dose, 
b. Received radiation therapy within 3 weeks before first dose, or 
c. Had major surgery within 4 weeks before first dose. 
3. Has received prior therapy with: 
a. Any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such 
as anti–PD-1, anti–PD-L1, or anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) 
antibodies 
b. For Phase 2: > 1 systemic treatment regimen for the advanced (recurrent, 
unresectable, or metastatic) cervical cancer for which the subject is considered for the 
study 

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Note: In Phase 1, prior treatment with a CTLA-4 antibody is permissible for subjects 
with metastatic melanoma. 
4. Has persisting toxicity related to prior therapy of NCI CTCAE Grade > 1 severity. 
Note: Sensory neuropathy or alopecia of Grade ≤ 2 is acceptable. 
5. Is expected to require any other form of systemic or localized antineoplastic therapy 
while on trial (including maintenance therapy with another agent, radiation therapy, 
and/or surgical resection). 
6. Has known severe hypersensitivity reactions to fully human monoclonal antibodies 
(National Cancer Institute Common Terminology Criteria for Adverse Events version 
4.03 [NCI CTCAE] Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma. 
7. Is receiving systemic corticosteroid ≤ 7 days prior to the first dose of trial treatment or 
receiving any other form of systemic immunosuppressive medication (corticosteroid use 
on study for management of immune-related adverse events, and/or a premedication for 
IV contrast allergies/reactions is allowed). Subjects who are receiving daily corticosteroid 
replacement therapy are an exception to this rule. Examples of permitted therapy are 
daily prednisone at doses of 5 to 7.5 mg or equivalent hydrocortisone dose, and steroid 
therapy administered by topical, intraocular, intranasal, and/or inhalation routes. 
8. Has a central nervous system (CNS) tumor, metastasis(es), and/or carcinomatous 
meningitis identified either on the baseline brain imaging obtained during the screening 
period OR identified prior to consent. 
Note: Subjects with history of brain metastases that have been treated may participate 
provided they show evidence of stable supra-tentorial lesions at screening (based on 
2 sets of brain images, performed ≥ 4 weeks apart, and obtained after the brain metastases 
treatment). In addition, any neurologic symptoms that developed either as a result of the 
brain metastases or their treatment must have resolved or be minimal and be expected as 
sequelae from treated lesions. For individuals who received steroids as part of brain 
metastases treatment, steroids must be discontinued ≥ 7 days prior to first dose of study 
drug. 
9. Has active or history of autoimmune disease that has required systemic treatment within 
2 years of the start of trial treatment (i.e., with use of disease modifying agents, 
corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, 
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary 
insufficiency, etc.) is not considered a form of systemic treatment. 
Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not 
requiring immunosuppressive treatment are eligible. 
10. Has had an allogeneic tissue/solid organ transplant. 
11. Has or had interstitial lung disease (ILD) OR has had a history of pneumonitis that has 
required oral or IV corticosteroids. 
12. Has an active infection requiring intravenous systemic therapy. 
13. Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 

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14. Has known active Hepatitis B, Hepatitis C or tuberculosis. Active Hepatitis B is defined 
as a known positive HBsAg result. Active Hepatitis C is defined by a known positive 
Hep C Ab result and known quantitative HCV RNA results greater than the lower limits 
of detection of the assay. 
15. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular 
accident/stroke or myocardial infarction within 6 months before enrollment, unstable 
angina, congestive heart failure (New York Heart Association class ≥ II), or serious 
uncontrolled cardiac arrhythmia requiring medication. 
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the trial, interfere with the subject’s participation for 
the full duration of the trial, or is not in the best interest of the subject to participate, in 
the opinion of the treating Investigator. 
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial. 
18. Is, at the time of signing informed consent, a regular user (including “recreational use”) 
of any illicit drugs or had a recent history (within the last year) of substance abuse 
(including alcohol). 
19. Is legally incapacitated or has limited legal capacity. 
20. Is pregnant or breastfeeding or expecting to conceive or father children within the 
projected duration of the trial, starting with the screening visit through 120 days after the 
last dose of study drug. 
4.4. 
Criteria for Subject Withdrawal 
4.4.1. 
Withdrawal from Treatment 
The subject must be withdrawn in the event of any of the following: 
• Occurrence of an event that would have been considered an exclusion criterion prior to 
enrollment, that is clinically relevant and affects the subject’s safety, and if 
discontinuation is considered necessary by the investigator and/or Sponsor. 
• Radiological disease progression, defined by RECIST 1.1 as defined in Section 6.4.4.3, 
unless the subject is considered to derive clinical benefit from the treatment by the 
investigator, is clinically stable and there is agreement with the Sponsor (Section 5.4.5). 
 
 
Clinical stability is defined by: 
− Absence of new symptoms and signs indicating clinically significant disease 
progression 
− No decline in ECOG performance status. 
− Absence of rapid progression of disease or progressive tumor at critical 
anatomical sites (e.g., cord compression) requiring urgent alternative medical 
intervention. 

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• Note: For Phase 2, tumor assessments should be performed every 6 weeks (± 3 days) 
from first treatment dose until discontinuation of treatment, regardless of reason for 
discontinuation. This includes patients who are being treated past disease progression. 
Clinical disease progression, in the absence of radiologic progression on the basis of 
RECIST 1.1, including 1 or more of the following: 
− signs and/or symptoms of consistent with clinically significant progression of 
disease, including worsening of laboratory values, appearance of new 
lesion/worsening of the lesion best seen clinically, etc. 
− decline in ECOG performance status 
− tumor progression at critical anatomical sites that requires urgent medical 
intervention (e.g., CNS metastasis with potential for cord progression) 
− initiation of chronic opiates, or initiation of chemotherapy or new antineoplastic 
therapy, palliative radiation therapy, or surgery 
• Any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to 
topical therapy and does not improve to Grade 1 severity within 2 weeks OR requires 
systemic treatment; 
• Any Grade ≥ 2 drug-related pneumonitis or interstitial lung disease that does not resolve 
to dose delay and systemic corticosteroids (also see Pulmonary Immune Related Adverse 
Event Management Algorithm [Section 5.6.3]); 
• Any Grade 2 or 3 drug-related toxicity that does not resolve in ≤ 6 weeks; 
• Any Grade 3 drug-related bronchospasm, hypersensitivity reaction, or infusion-related 
reaction, regardless of duration; with the exception of Grade 3 infusion-related reactions 
resolving within 6 hours and controlled with medical management; 
• Any Grade 3 non-skin, drug-related AE lasting > 7 days, with the following exceptions 
for uveitis, pneumonitis, bronchospasm, diarrhea, colitis, neurologic toxicity, 
hypersensitivity reactions, infusion reactions, endocrinopathies, and laboratory 
abnormalities: 
− Grade 3 drug-related uveitis, pneumonitis, bronchospasm, diarrhea, colitis, 
neurologic toxicity, hypersensitivity reaction, or infusion reaction of any duration 
requires discontinuation; 
− Grade 3 drug-related endocrinopathies adequately controlled with only 
physiologic hormone replacement do not require discontinuation; 
− Grade 3 drug-related laboratory abnormalities do not require treatment 
discontinuation except: 
▪ 
Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding 
requires discontinuation; 
▪ 
Any drug-related liver function test (LFT) abnormality that meets the 
following criteria require discontinuation (also see hepatic immune-related AE 
management algorithm [Table 7]): 

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► AST or ALT > 8 x ULN; 
► Total bilirubin > 5 x ULN; 
► Concurrent AST or ALT > 3 x ULN AND total bilirubin > 2 x ULN; 
• Any Grade 4 drug-related AE or laboratory abnormality, except for the following events, 
which do not require discontinuation: 
− Grade 4 neutropenia <7 days; 
− Grade 4 lymphopenia or leukopenia; 
− Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with 
clinical sequelae and are corrected with supplementation/appropriate management 
within 72 hours after their onset; 
• Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
Investigator, presents a substantial clinical risk to the subject with continued treatment; 
• Tumor flare phenomenon, defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor does not require treatment discontinuation. 
• Any requirement for ≥ 10 mg per day of prednisone (or equivalent) for > 6 weeks; 
• Any recurrence of a Grade 3 or 4 drug-related toxicity; 
• Dose delay which results in no AGEN2034 dosing for more than 6 weeks. 
• Occurrence of AEs, resulting in discontinuation of trial drug that is desired or considered 
necessary by the investigator and/or the subject (if applicable). 
• Occurrence of pregnancy (if applicable). 
• Use of a non-permitted concomitant drug, as defined in Section 5.5.2, in which the 
predefined consequence is withdrawal from study drug (Sponsor may be contacted to 
discuss whether trial treatment must be discontinued). 
• Noncompliance for non-medical reasons (Section 6.4.1.11) 
4.4.2. 
Withdrawal from the Trial 
Subjects are free to discontinue the trial at any time without giving their reasons. A subject must 
be withdrawn in the event of any of the following: 
• Withdrawal of the subject’s consent. 
• Participation in any other therapeutic trial during the treatment duration of this trial. 
If a subject has failed to attend scheduled trial assessments, the investigator must determine the 
reasons and the circumstances as completely and accurately as possible. 

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In case of premature withdrawal from the trial, the investigations scheduled for the 
Discontinuation Visit should be performed (Section 6.1) if possible, with focus on the most 
relevant assessments. In any case, the appropriate electronic case report form (eCRF) section 
must be completed. 
4.4.3. 
Premature Discontinuation of the Trial 
The entire trial may be discontinued prematurely in the event of any of the following: 
• New information leading to unfavorable risk-benefit judgement of AGEN2034, e.g., due 
to: 
- 
Occurrence of significant previously unknown adverse reactions, or unexpectedly 
high intensity or incidence of known adverse reactions. 
- 
Other unfavorable safety findings. 
Note: Evidence of inefficacy may arise from this trial or from other trials of 
AGEN2034, and unfavorable safety findings may arise from clinical or non-clinical 
examinations (e.g., toxicology). 
• Sponsor’s decision that continuation of the trial is unjustifiable for medical or ethical 
reasons. 
• Poor enrollment of subjects, making completion of the trial within an acceptable 
timeframe unlikely. 
• Discontinuation of development of AGEN2034. 
Health authorities and Independent Ethics Committees (IECs)/Institutional Review Boards 
(IRBs) will be informed about trial discontinuation in accordance with applicable regulations. 
The entire trial may be terminated or suspended upon request of health authorities. 
5. 
STUDY DRUGS AND TREATMENT 
5.1. 
Investigational Medicinal Product 
The investigational medicinal product (IMP), also known as study drug, is AGEN2034, a novel, 
fully human monoclonal IgG4 antibody designed to block PD-1.  
AGEN2034 drug product is supplied as a sterile, single-use solution for IV injection in a 2 mL or 
10 mL glass vial. AGEN2034 should be stored in a refrigerator at 2°C to 8°C. 
Each drug product 2 mL vial contains a withdrawable volume of 1 mL with 50 mg AGEN2034 
at a nominal concentration of 50 mg/mL formulated in
 
. Each drug product 10 mL vial contains a withdrawable volume of 
5 mL with 50 mg AGEN2034 at a nominal concentration of 10 mg/mL formulated in 
 
. 

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Please refer to the current version of the Investigator’s Brochure and/or Pharmacy Manual for 
complete storage, handling, dispensing, and infusion information for AGEN2034. 
5.2. 
Packaging and Labeling 
Study drug packaging and labeling will be in accordance with applicable local regulatory 
requirements and applicable Good Manufacturing Practice guidelines. The following information 
will be pre-printed on the vial: vial contents, storage conditions, and lot number. The label will 
also contain a statement to conform with FDA Investigational New Drug (IND) requirements as 
follows: 
“Caution: New Drug - Limited by federal law to investigational use.” 
All study drug must be kept in a secure place under appropriate storage conditions. The sponsor 
or its representatives must be granted access on reasonable request to check drug storage, 
dispensing procedures, and accountability records. Refer to the Pharmacy Manual for additional 
details. 
5.3. 
Storage and Dispensing 
The product storage manager should ensure that study drugs are stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined in the Pharmacy 
Manual. If concerns regarding the quality or appearance of the study drug arise, the study drug 
should not be dispensed and Sponsor should be contacted immediately. 
Study drug documentation must be maintained including all processes required to ensure drug is 
accurately administered. This includes documentation of drug storage, administration and, as 
applicable, storage temperatures, reconstitution, and use of required processes (e.g., required 
diluents, administration sets). 
AGEN2034 will be shipped in transport cool containers (2°C to 8°C) that are monitored with 
temperature control devices. 
AGEN2034 drug product must be stored at 2°C to 8°C until use, with a temperature log 
maintained daily. All medication boxes supplied to each study center must be stored carefully, 
safely, and separately from other drugs. 
For application in this trial, AGEN2034 drug product must be diluted with 0.9% saline solution 
(sodium chloride injection). Detailed information on infusion bags and medical devices to be 
used for preparation of dilutions and subsequent administration is provided in the Pharmacy 
Manual. 
Once the vial is punctured, the AGEN2034 drug product must be diluted into appropriate volume 
of 0.9% saline solution in an infusion bag immediately. Infusion from the bag should begin 
within 24 hours of vial puncture when the bag is stored either at room temperature or at 5°C 
± 3°C (refrigerated conditions). 
Any unused portion of solution should be discarded in biohazard waste disposal, with final 
disposal by accepted local and national standards of incineration. 
Please refer to the current version of the Investigator’s Brochure and/or Pharmacy Manual for 
complete storage, handling, dispensing, and infusion information for AGEN2034. 

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5.4. 
Dosage and Administration 
5.4.1. 
AGEN2034 
AGEN2034 infusions should be administered within 60 minutes (-10/+20 min) using an infusion 
pump. A central catheter is not required for infusion; however, if a subject has a central venous 
catheter in place, it is recommended that it be used for the infusion. Once the infusion is 
completed, all remaining drug solution in the line should be administered according to 
institutional guidelines for saline flushing. 
5.4.1.1. 
Treatment Regimen 
In Phase 1, the dose levels and schedules shown in Table 2 will be studied. 
Table 2: Phase 1 Dosing Regimens 
Part and Agent 
Dose 
Schedule 
Duration of Treatment 
Part A1: Dose Level 1 
 
 
 
 
AGEN2034 
1 mg/kg IV1 
Every 2 weeks 
Up to 24 months 
Part A1: Dose Level 2 
 
 
 
 
AGEN2034 
3 mg/kg IV1 
Every 2 weeks 
Up to 24 months 
Part A1: Dose Level 3 
 
 
 
 
AGEN2034 
10 mg/kg IV1 
Every 2 weeks 
Up to 24 months 
Part A2: Dose Level 1 
 
 
 
 
AGEN2034 
6 mg/kg IV1 
Every 3 weeks 
Up to 24 months 
Part A2: Dose Level 2 
 
 
 
 
AGEN2034 
10 mg/kg IV1 
Every 3 weeks 
Up to 24 months 
1 Infusion time is 60 minutes (-10/+20 min) 
 
In Phase 2, all subjects will receive AGEN2034 at a dose of 3 mg/kg IV over 60 minutes 
(-10/+20 min) every 2 weeks for up to 24 months. 
In both Phases, subjects will be treated for up to 24 months, regardless of dose delays, as long as 
the subject meets criteria to remain on therapy. 
5.4.2. 
Premedication 
Premedication should not be administered routinely prior to dosing of drugs. See Section 5.4.3 
for subsequent premedication recommendations following AGEN2034-related infusion 
reactions. 
5.4.3. 
Treatment of Infusion Related Reactions 
Acute infusion reactions (which can include cytokine release syndrome, angioedema, or 
anaphylaxis) are different from allergic/hypersensitive reactions, although some of the 
manifestations are common to both AEs. Signs and symptoms usually develop during or shortly 

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after drug infusion and generally resolve completely within 24 hours of completion of infusion. 
Signs/symptoms may include: allergic reaction/hypersensitivity (including drug fever); arthralgia 
(joint pain); bronchospasm; cough; dizziness; dyspnea (shortness of breath); fatigue (asthenia, 
lethargy, malaise); headache; hypertension; hypotension; myalgia (muscle pain); nausea; 
pruritus/itching; rash/desquamation; rigors/chills; sweating (diaphoresis); tachycardia; tumor 
pain (onset or exacerbation of tumor pain due to treatment); urticaria (hives, welts, wheals); 
vomiting. 
For an individual subjects, once the AGEN2034 infusion rate has been decreased by 50% or 
interrupted due to an infusion-related reaction, it must remain decreased for all subsequent 
infusions to that subject. If the subject has a second infusion-related reaction that is Grade ≥ 2 on 
the slower infusion rate, infusion should be stopped and the subject should discontinue treatment. 
If a subject experiences a Grade 3 or Grade 4 infusion-related reaction at any time, the subject 
must discontinue treatment. If an infusion reaction occurs, all details about drug preparation and 
infusion must be recorded. 
Should infusion reaction be considered a significant safety issue by the SMC, the SMC might 
decide to recommend premedication with an antihistamine and acetaminophen approximately 30 
to 60 minutes before each dose of AGEN2034 (e.g., 25–50 mg diphenhydramine, 500–650 mg 
paracetamol IV or oral equivalent acetaminophen). This regimen may be modified based on local 
treatment standards and guidelines, as appropriate. 
Table 3 shows treatment guidelines for subjects who experience an infusion reaction associated 
with administration of AGEN2034. 
Subjects receiving AGEN2034 should be monitored for infusion reactions. This includes the 
measurement of vital signs for at least 1 hour after infusion. Subjects will remain in the clinic 
under close supervision for the duration of this monitoring period. Subjects with mild or 
moderate infusion reactions may receive AGEN2034 with close monitoring. Premedication with 
an antipyretic or antihistamine for subsequent treatment administration may be considered. For 
severe infusion reactions, AGEN2034 infusion must be discontinued, and appropriate medical 
therapy should be administered.  
Subjects who do not experience any infusion related toxicity Grade 1 or higher during or after 
the infusion may be released from monitoring after one hour if they are otherwise stable. 
Subjects with any infusion related toxicity must be managed as per the guidelines in Table 3 and 
monitoring will continue until any infusion related toxicity has abated to less than Grade 1 and at 
least one hour has passed from the completion of the entire infusion and flush. All subjects will 
be given information on and instructions regarding both infusion related toxicity, which is 
expected to be most likely in the hour after completion of the infusion, and immune related AEs, 
before leaving the study site. This will include instructions on when and how to return for 
immune mediated toxicities associated with PD-1 blockade. 
Once the AGEN2034 infusion rate has been decreased by 50% or interrupted due to an infusion- 
related reaction, it must remain decreased for all subsequent infusions. If the subject has a second 
infusion-related reaction that is Grade ≥ 2 on the slower infusion rate, infusion should be stopped 
and the subject should discontinue treatment. If a subject experiences a Grade 3 or Grade 4 
infusion-related reaction at any time, the subject must discontinue treatment. If an infusion 
reaction occurs, all details about drug preparation and infusion must be recorded. 

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Should infusion reaction be considered a significant safety issue by the SMC, the SMC might 
decide to recommend premedication with an antihistamine and acetaminophen approximately 
30 to 60 minutes before each dose of AGEN2034 (e.g., 25-50 mg diphenhydramine, 500-650 mg 
paracetamol IV or oral equivalent acetaminophen). This regimen may be modified based on local 
treatment standards and guidelines, as appropriate. 
 

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Table 3: AGEN2034 Infusion Related Reaction Management Guidelines 
CTCAE Grade 
Treatment 
Premedication at 
Subsequent Dose 
Grade 1: 
Mild reaction; infusion 
interruption not 
indicated; intervention 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion 
of the investigator. 
None. 
Grade 2: 
Requires infusion interruption 
but responds promptly to 
symptomatic treatment 
(e.g., antihistamines, 
nonsteroidal anti-inflammatories 
[NSAIDS], narcotics, IV fluids); 
prophylactic medications 
indicated for ≤ 24 hours. 
Stop infusion and monitor symptoms. 
Additional appropriate medical therapy 
may include but is not limited to the 
following: 
• IV fluids 
• Antihistamines 
• NSAIDS 
• Acetaminophen 
• Narcotics 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion 
of the investigator. 
If symptoms resolve within 1 hour of 
stopping drug infusion, the infusion may be 
restarted at 50% of the original infusion 
rate. Otherwise, dose administration will be 
held until symptoms resolve, and the 
subject should be premedicated for the next 
scheduled dose. 
Subjects who develop Grade 2 toxicity 
despite adequate premedication should be 
permanently discontinued from further 
Subject may be pre-medicated 
1.5 hours (± 30 minutes) prior to 
infusion with the following: 
• Diphenhydramine 50 mg 
PO (or equivalent dose of 
antihistamine). 
• Acetaminophen 500-1000 
mg PO (or equivalent dose 
of antipyretic). 
Grades 3 or 4 
Grade 3: 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial 
improvement; hospitalization 
indicated for other clinical 
sequelae (e.g., renal 
impairment, pulmonary 
infiltrates). 
Grade 4: 
Life-threatening; pressor or 
ventilatory support 
indicated. 
Stop infusion. 
Additional appropriate medical therapy 
may include but is not limited to: 
• IV fluids 
• Antihistamines 
• NSAIDS 
• Acetaminophen 
• Narcotics 
• Oxygen 
• Pressors 
• Corticosteroids 
• Epinephrine 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion 
of the investigator. 
Hospitalization may be indicated. 
Subject is permanently discontinued 
from further study drug administration. 
No subsequent dosing. 
 

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5.4.4. 
Dose Modifications and Treatment Delay 
5.4.4.1. 
Dose Reductions 
No AGNE2034 dose reduction or escalation is allowed. Each subject will stay on the dose 
levels assigned in the trial unless treatment needs to be stopped.  
5.4.4.2. 
Treatment Delay 
5.4.4.2.1. Criteria for Treatment Delay 
AGEN2034 administration should be delayed for the following: 
• Any Grade ≥ 2 non-skin, drug-related AE with the following exceptions: 
− Do not delay treatment for Grade ≥ 2 Fatigue and laboratory abnormalities except 
for: 
▪ 
Delay dosing for Grade ≥ 2 serum creatinine (more than 1.5x baseline) toxicity 
▪ 
If a subject has a baseline AST, ALT, or total bilirubin that is within normal 
limits, delay dosing for drug-related Grade ≥ 2 toxicity; 
• Any Grade ≥ 3 skin drug-related AE or suspected Stevens-Johnson syndrome (SJS) or 
toxic epidermal necrolysis (TEN) 
• Any Grade ≥ 3 drug-related laboratory abnormality with the following exceptions for 
lymphopenia, AST, ALT, or total bilirubin: 
− Grade 3 lymphopenia does not require a dose delay. 
− If a subject has a baseline AST, ALT, or total bilirubin that is within normal 
limits, delay dosing for drug-related Grade ≥ 2 toxicity. 
− If a subject has baseline AST, ALT, or total bilirubin within the Grade 1 toxicity 
range, delay dosing for drug-related Grade ≥ 3 toxicity. 
• Any AE, laboratory abnormality, or inter-current illness which, in the judgment of the 
investigator, warrants delaying the dose of study drug. 
Subjects receiving AGEN2034 who have drug-related toxicities that meet the criteria for dose 
delay should have treatment delayed until retreatment criteria are met. 
5.4.4.2.2. Criteria to Resume Treatment 
Subjects may resume treatment with AGEN2034 when drug-related AE(s) resolve(s) to Grade 1 
or baseline value, with the following exceptions: 
• Subjects may resume treatment in the presence of Grade 2 fatigue. 
• Subjects who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity. 

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• Subjects with baseline Grade 1 AST/ALT or total bilirubin who require dose delays 
for reasons other than a 2-Grade shift in AST/ALT or total bilirubin may resume 
treatment in the presence of Grade 2 AST/ALT or total bilirubin. 
− Subjects with combined Grade 2 AST/ALT AND total bilirubin values meeting 
discontinuation parameters (Section 4.4.1) should have treatment permanently 
discontinued. 
• Drug-related pulmonary toxicity, diarrhea, or colitis must have resolved to baseline 
before treatment is resumed. 
• Drug-related endocrinothapies adequately controlled with only physiologic hormone 
replacement may resume treatment. 
• Subjects who received systemic corticosteroids for management of any drug-related 
toxicity must be off corticosteroids or have tapered down to an equivalent dose of 
prednisone ≤ 10 mg/day. 
5.4.5. 
Treatment Beyond Disease Progression 
Subjects will be permitted, with the Sponsor’s approval, to continue with treatment beyond 
initial RECIST 1.1 defined progressive disease (PD) as long as they meet the following criteria: 
• Investigator-assessed clinical benefit from the treatment; 
• Is clinically stable (see definition in Section 4.4.1); 
• Subject is tolerating study drug; and 
• There is agreement with the sponsor. 
The assessment of clinical benefit should take into account whether the subject is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. The following 
criteria need to be taken into consideration: 
• Absence of clinical symptoms and signs (including worsening of laboratory values) 
indicating disease progression. 
• No decline in ECOG performance status. 
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (e.g., cord compression) requiring urgent alternative medical intervention. 
Subjects should discontinue study therapy upon evidence of further progression, defined as an 
additional 10% or greater increase in tumor burden from time of initial progression (including all 
target lesions and new measurable lesions). 
Imaging is required every 6 weeks (± 3 days) for those subjects with PD who remain on 
AGEN2034 until treatment is discontinued. 
At the time of initial progression, new lesions are considered measurable if the longest diameter 
is ≥ 10 mm (except for pathological lymph nodes, which must have a short axis of ≥ 15 mm). 
Any new lesion considered non-measurable at the time of initial progression may become 
measurable and therefore included in the tumor burden measurement if the longest diameter 

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increases to ≥ 10 mm (except for pathological lymph nodes, which must have an increase in 
short axis to ≥ 15 mm). 
5.5. 
Concomitant Treatments 
5.5.1. 
Acceptable Concomitant Medications 
All treatments that the investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care. All concomitant medication will be recorded on the eCRF including all 
prescription, over-the-counter (OTC), herbal supplements, and IV medications and fluids. If 
changes occur during the trial period, documentation of drug dosage, frequency, route, and date 
will also be included on the eCRF. 
Palliative and supportive care is permitted during the course of the trial for underlying medical 
conditions and management of symptoms. 
Surgery for tumor control or symptom management is not permitted during the study. Palliative 
radiotherapy is permitted to a single lesion if considered medically necessary by the treating 
physician as long as the lesion is NOT a RECIST 1.1-defined target lesion and treatment is NOT 
administered for tumor control. Trial therapy should be held during the course of palliative 
radiotherapy and should be resumed no earlier than the next scheduled administration of trial 
therapy. The specifics of the radiation treatment, including the location, will be recorded. 
All concomitant medications received within 30 days before the first dose of trial treatment 
through the Safety Follow-up Visit should be recorded. 
5.5.1.1. 
Rescue Medications and Supportive Care 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating investigator including but not limited to the items outlined below. 
For guidelines for continuing treatment with AGEN2034, see Section 5.4.4.2.2. 
• Diarrhea: Subjects should be carefully monitored for signs and symptoms of 
enterocolitis (such as diarrhea, abdominal pain, blood or mucus in stool, with or 
without fever) and of bowel perforation (such as peritoneal signs and ileus). In 
symptomatic subjects, infectious etiologies should be ruled out, and if symptoms are 
persistent and/or severe, endoscopic evaluation should be considered. All subjects 
who experience diarrhea should be advised to drink liberal quantities of clear fluids. 
If sufficient oral fluid intake is not feasible, fluid and electrolytes should be 
substituted via IV infusion. 
• Anemia: Transfusions and/or erythropoietin may be utilized as clinically indicated for 
the treatment of anemia, but should be clearly noted as concurrent medications. 
Consider a potential immunologic etiology. 
• Neutropenia: Prophylactic use of colony-stimulating factors including Granulocyte 
Colony- Stimulating Factor (G-CSF), PEGylated G-CSF or Granulocyte Macrophage 
Colony- Stimulating Factor GM CSF is not allowed in this trial. Therapeutic use of 

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G-CSF is allowed in subjects with Grade 3-4 febrile neutropenia. Consider a potential 
immunologic etiology. 
• Thrombocytopenia: Transfusion of platelets may be used if clinically indicated. 
Immune thrombocytopenia purpura (ITP) should be ruled out before initiation of 
platelet transfusion. 
• Anti-infectives: Subjects with a documented infectious complication should receive 
oral or IV antibiotics or other anti-infective agents as considered appropriate by the 
treating Investigator for a given infectious condition, according to standard 
institutional practice. 
• Adverse event with a potential immunologic etiology (irAE): identification, 
evaluation and management of adverse experiences of a potential immunologic 
etiology. Depending on the type and severity of an irAE, oral or intravenous 
treatment with a corticosteroid should be considered, in addition to appropriate 
symptomatic treatment of a given condition (see Section 5.6 for management 
algorithms). These are also considered AEs of special interest (AESI) and should be 
reported to the Sponsor per Section 7.2.2.2. 
5.5.2. 
Prohibited and/or Restricted Treatments 
As stated in the exclusion criteria (Section 4.3), subjects must not have had chemotherapy, 
radiotherapy (other than palliative bone-directed radiotherapy, as described in Section 5.5.1), 
major surgery, or received another investigational agent within 28 days before the start of study 
treatment. 
Subjects are prohibited from receiving the following therapies and treatments during the 
Screening and Treatment periods of this trial: 
• Immunotherapy not specified in this protocol. 
• Chemotherapy. 
• Investigational agents other than AGEN2034. 
• Surgery for symptom management or tumor control. 
• Growth factors (granulocyte colony-stimulating factor or granulocyte macrophage 
colony- stimulating factor). Exception: Erythropoietin and darbepoietin alpha may be 
prescribed at the investigator’s discretion. Therapeutic use of G-CSF is allowed in 
subjects with Grade 3 or 4 febrile neutropenia. 
• Radiation therapy for tumor control. 
• Glucocorticoids for any purpose other than to modulate symptoms from an irAE, or 
for use as a pre-medication in subjects with a known history of an IV contrast allergy 
administered as part of computed tomography (CT) radiography. 
Note: Replacement doses of corticosteroids (for example, prednisone 5-7.5 mg daily) are 
permitted while on study. 
Note: Use of inhaled or topical corticosteroid is permitted. 

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• Bisphosphonates and/or receptor activator of nuclear factor kappa-B ligand (RANKL) 
inhibitor therapies cannot be initiated after informed consent has been signed. These 
therapies may be continued IF treatment with an agent from one of these two classes 
was initiated PRIOR to signing informed consent. 
• Subjects who, in the assessment by the investigator, require the use of any of the 
aforementioned treatments for clinical management should be removed from the trial. 
• Subjects may receive other medications that the investigator deems to be medically 
necessary. 
• Medications listed in the Exclusion Criteria are prohibited in this trial. 
• There are no prohibited therapies during the Post-Treatment Follow-up Phase 
5.5.3. 
Other Restrictions and Precautions 
The following non-drug therapies must not be administered or performed during the study (and 
within 28 days before the start of trial treatment): 
• Major surgery (excluding prior diagnostic biopsy). 
• Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or that 
are known to potentially interfere with major organ function (e.g., hypericin). 
• Subjects should not abuse alcohol or other drugs during the study. 
5.6. 
Management of Immune-related Adverse Events  
Immuno-oncology agents such as AGEN2034 are associated with irAEs. Early recognition and 
management of irAEs may mitigate severe toxicity. Investigators should also monitor subjects 
closely for potential irAEs, which may manifest at the earliest after weeks of treatment. Such 
events may consist of persistent rash, diarrhea, colitis, autoimmune hepatitis, pneumonitis, 
encephalitis, arthritis, glomerulonephritis, cardiomyopathy, or uveitis and other inflammatory 
eye conditions. 
Management Algorithms have been developed to assist investigators in assessing and managing 
the following groups of irAEs: Gastrointestinal, Pulmonary, Dermatological, Renal, Hepatic, 
Neurological, and Endocrine among others. 
Adverse events (both non-serious and serious) associated with drug exposure and consistent with 
an immune phenomenon may represent an immunologic etiology. These immune related AEs 
may be predicted based on the nature of the study drugs, their mechanism of action, and reported 
experience with immunotherapies that have a similar mechanism of action. An irAE can occur 
shortly after the first dose or several months after the last dose of study drug. Particular attention 
should be paid to AEs that may be suggestive of potential irAEs as outlined below. 
Immune-related AEs are considered are considered AESIs and should be reported to the Sponsor 
per Section 7.2.2.2. 

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5.6.1. 
Dermatological Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. 
 
Table 4: Dermatological Immune-related Adverse Event Management Algorithm 
Dermatological Immune-related Adverse Events 
Grade of Rash 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1–2 
Covering ≤30% body surface 
area. 
• Symptomatic therapy (e.g., 
antihistamines, topical 
corticosteroids). 
• Continue AGEN2034 therapy 
per protocol. 
• If persists >1 to 2 weeks or recurs: 
Consider skin biopsy. 
• Delay AGEN2034 therapy. 
• Consider 0.5–1 mg/kg/day 
methylprednisolone IV or oral 
equivalent. Once improving, taper 
corticosteroids over at least 1 month; 
consider prophylactic antibiotics for 
opportunistic infections; and resume 
AGEN2034 therapy per protocol. 
• If worsens: treat as Grade 3–4. 
Grade 3–4 
Covering >30% body surface 
area; life-threatening 
consequences. 
• Delay or discontinue 
AGEN2034 therapy per 
protocol. 
• Consider skin biopsy. 
• Dermatology consult 
• 1–2 mg/kg/day 
methylprednisolone IV or IV 
equivalent. 
• If improves to Grade 1: taper 
corticosteroids over at least 1 month; 
add prophylactic antibiotics for 
opportunistic infections. 
• Resume AGEN2034 therapy per 
protocol. 
 
 
 

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5.6.2. 
Gastrointestinal Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy. Opiates/narcotics may mask symptoms of perforation. Infliximab should not be 
used in cases of perforation or sepsis. 
 
Table 5: Gastrointestinal Immune-related Adverse Event Management Algorithm 
Gastrointestinal Immune-related Adverse Events 
Severity of Diarrhea/Colitis 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1 
Diarrhea: <4 stools/day over 
baseline. 
Colitis: asymptomatic. 
• Continue AGEN2034 therapy 
per protocol. 
• Symptomatic treatment 
• Close monitoring for worsening 
symptoms. 
• Educate subject to report worsening 
immediately. 
• Consider symptomatic treatment 
including hydration, electrolyte 
replacement, dietary changes (e.g. 
American Dietetic Association colitis 
diet), and loperamide 
• If worsens: treat as Grade 2 or 3–4. 
Grade 2 
Diarrhea: 4–6 stools per day 
over baseline; IV fluids 
indicated <24 h; not interfering 
with activities of daily living 
(ADL). 
Colitis: abdominal pain; blood 
in stool 
• Delay AGEN2034 therapy 
per protocol. 
• Symptomatic treatment. 
• If improves to Grade 1: resume 
AGEN2034 therapy per protocol. 
• If persists >5 to 7 days or recurs: 0.5–
1 mg/kg/day methylprednisolone or 
equivalent. 
• When symptoms improve to Grade 1, 
taper corticosteroids over at least 
1 month; consider prophylactic 
antibiotics for opportunistic infections; 
resume AGEN2034 therapy per 
protocol. 
• If worsens or persists >3 to 5 days with 
oral corticosteroids: treat as Grade 3–4. 
Grade 3 to 4 
Diarrhea (Grade 3): ≥7 stools 
per day over baseline; 
incontinence; IV fluids ≥24 h; 
interfering with ADL. 
Colitis (Grade 3): severe 
abdominal pain, medical 
intervention indicated, 
peritoneal signs. 
Grade 4: life-threatening, 
perforation 
• Discontinue AGEN2034 
therapy per protocol. 
• 1–2 mg/kg/day 
methylprednisolone IV or 
equivalent. 
• Add prophylactic antibiotics 
for opportunistic infections. 
• Consider lower endoscopy. 
• If improves: continue corticosteroids 
until Grade 1, then taper over at least 1 
month. 
• If persists >3 to 5 days, or recurs after 
improvement: add infliximab 5 mg/kg 
(if no contraindication). 
Note: infliximab should not be used in 
cases of perforation or sepsis. 
  

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5.6.3. 
Pulmonary Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. Evaluate with imaging and pulmonary consultation. 
 
Table 6: Pulmonary Immune-related Adverse Event Management Algorithm 
Pulmonary Immune-related Adverse Events 
Grade of Pneumonitis 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1 
Radiographic changes only. 
• Consider delay of 
AGEN2034 therapy per 
protocol. 
• Monitor for symptoms every 
2–3 days. 
• Consider pulmonary and 
infectious disease consults. 
• Re-image every ≥3 weeks. 
• If worsens: treat as Grade 2 or Grade 
3–4. 
Grade 2 
Mild to moderate new 
symptoms 
• Delay AGEN2034 therapy 
per protocol. 
• Pulmonary and infectious 
disease consults. 
• Monitor symptoms daily; 
consider hospitalization. 
• 1 mg/kg/day 
methylprednisolone IV or 
oral equivalent. 
• Consider bronchoscopy, lung 
biopsy. 
• Re-image every 1–3 days. 
• If improves: when symptoms return to 
near baseline, taper corticosteroids over 
at least 1 month, then resume 
AGEN2034 therapy per protocol, and 
consider prophylactic antibiotics. 
• If not improving after 2 weeks or 
worsening: treat as Grade 3–4. 
Grade 3–4 
Severe new symptoms; new/ 
worsening hypoxia; life- 
threatening. 
• Discontinue AGEN2034 
therapy per protocol. 
• Hospitalize. 
• Pulmonary and infectious 
disease consults. 
• 2–4 mg/kg/day 
methylprednisolone IV or IV 
equivalent. 
• Add prophylactic antibiotics 
for opportunistic infections. 
• Consider bronchoscopy, lung 
biopsy. 
• If improves to baseline: taper 
corticosteroids over at least 6 weeks. 
• If not improving after 48 hours or 
worsening: add additional 
immunosuppression (e.g., infliximab, 
cyclophosphamide, IV 
immunoglobulin, mycophenolate 
mofetil). 
 
 
 

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5.6.4. 
Hepatic Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. Consider imaging for obstruction. 
 
Table 7: Hepatic Immune-related Adverse Event Management Algorithm 
Hepatic Immune-related Adverse Events 
Grade of Liver Test Elevation 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1 
AST or ALT >ULN to 3 x ULN 
and/or total bilirubin >ULN to 
1.5 x ULN. 
• Continue AGEN2034 therapy 
per protocol. 
• Continue liver function tests (LFT) 
monitoring per protocol. 
• If worsens: treat as Grade 2 or Grade 
3–4. 
Grade 2 
AST or ALT >3 to ≤5 x ULN 
and/or total bilirubin >1.5 to 
≤3 x ULN. 
• Delay AGEN2034 therapy 
per protocol. 
• Increase frequency of 
monitoring to every 
3 days. 
• If subject has concurrent AST 
or ALT > 3 x ULN AND 
total bilirubin > 2 x ULN, 
Discontinue AGEN2034 
therapy per protocol. 
• If returns to baseline: resume routine 
monitoring; resume AGEN2034 
therapy per protocol. 
• If elevations persist >5 to 7 days or 
worsen: 0.5–1 mg/kg/day 
methylprednisolone IV or oral 
equivalent. When LFT returns to Grade 
1 or baseline, taper corticosteroids over 
at least 1 month, consider prophylactic 
antibiotics for opportunistic infections, 
and resume AGEN2034 therapy per 
protocol. 
Grade 3–4 
AST or ALT >5 x ULN and/or 
total bilirubin >3 x ULN. 
• Discontinue AGEN2034 
therapy per protocol. 
• Increase frequency of 
monitoring to every 
1–2 days. 
• 1–2 mg/kg/day 
methylprednisolone IV or 
oral equivalent*. 
• Add prophylactic antibiotics 
for opportunistic infections. 
• Consult gastroenterology. 
• Consider obtaining MRI/CT 
scan of liver and liver biopsy 
if clinically warranted. 
• If returns to Grade 2: taper 
corticosteroids over at least 1 month. 
• If does not improve in > 3 to 5 days, 
worsens or rebounds: add 
mycophenolate mofetil 1 g twice daily. 
If no response within an additional 
3-5 days, consider other 
immunosuppressants per local 
guidelines. 
*The recommended starting dose for Grade 4 hepatitis is 2 mg/kg/day methylprednisolone IV. 
 
 
 

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5.6.5. 
Endocrine Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. Consider visual field testing, endocrinology consultation, and 
imaging. 
 
Table 8: Endocrine Immune-related Adverse Event Management Algorithm 
Endocrine Immune-related Adverse Events 
Endocrine Disorder 
Management 
Follow-Up 
Asymptomatic 
thyroid-stimulating 
hormone (TSH) 
abnormality 
• Continue AGEN2034 therapy per protocol. 
• If TSH < 0.5 x lower limit of normal (LLN) or TSH > 2 x ULN, or 
consistently out of range in 2 subsequent measurements: include free 
thyroxine (fT4) at subsequent cycles as clinically indicated; consider 
endocrinology consult. 
Symptomatic endocrinopathy 
• Evaluate endocrine function. 
• Consider pituitary scan. 
• Symptomatic with 
abnormal lab/pituitary 
scan: delay AGEN2034 
therapy per protocol; 
1-2 mg/kg/day 
methylprednisolone IV or 
oral equivalent; initiate 
appropriate hormone therapy. 
• No abnormal lab/ pituitary 
MRI scan but symptoms 
persist: repeat labs in 
1-3 wk/MRI in 1 month. 
• If improves (with or without 
hormone replacement): taper 
corticosteroids over at least month and 
consider prophylactic antibiotics for 
opportunistic infections. 
• Resume AGEN2034 therapy per 
protocol. 
• Subjects with adrenal insufficiency may 
need to continue corticosteroids with 
mineralocorticoid component. 
Suspicion of adrenal crisis 
(e.g., severe dehydration, 
hypotension, shock out of 
proportion to current illness) 
• Delay or discontinue AGEN2034 therapy per protocol. 
• Rule out sepsis. 
• Stress dose of IV corticosteroids with mineralocorticoid activity. 
• IV fluids. 
• Consult endocrinologist. 
• If adrenal crisis ruled out, treat as above for symptomatic endocrinopathy. 
 
 
 

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5.6.6. 
Renal Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. 
 
Table 9: Renal Immune-related Adverse Event Management Algorithm 
Renal Immune-related Adverse Events 
Grade of Creatinine Elevation 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1 
Creatinine > upper limit of normal 
(ULN) and > than baseline but ≤ 
1.5x baseline. 
• Continue AGEN2034 
therapy per protocol. 
• Monitor creatinine weekly 
• If returns to baseline: resume routine 
creatinine monitoring per protocol. 
• If worsens: treat as Grade 2 or Grade 
3–4. 
Grade 2-3 
Creatinine > 1.5x baseline to ≤ 6x 
ULN. 
• Delay AGEN2034 therapy 
per protocol. 
• Monitor creatinine every 2- 
3 days 
• 0.5 to 1.0 mg/kg/day 
methylprednisolone IV or 
oral equivalent. 
• Consider renal biopsy 
• If returns to Grade 1: taper 
corticosteroids over at least 1 month, 
consider prophylactic antibiotics for 
opportunistic infections, and resume 
AGEN2034 therapy and routine 
creatinine monitoring per protocol. 
• If elevations persist > 7 days or worsen: 
treat as Grade 4. 
Grade 4 
Creatinine > 6x ULN. 
• Discontinue AGEN2034 
therapy per protocol. 
• Monitor creatinine daily. 
• 1.0 to 2.0 mg/kg/day 
methylprednisolone IV or 
IV equivalent. 
• Consult nephrologist. 
• Consider renal biopsy 
• If returns to Grade 1: taper 
corticosteroids over at least 1 month 
and add prophylactic antibiotics for 
opportunistic infections. 
 
 
 

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5.6.7. 
Neurological Immune-related Adverse Events 
Rule out non-inflammatory causes, if non-inflammatory cause is identified, treat accordingly and 
continue therapy per protocol. 
 
Table 10: Neurological Immune-related Adverse Event Management Algorithm 
Neurological Immune-related Adverse Events 
Grade of Neurological Toxicity 
(NCI CTCAE v4.03) 
Management 
Follow-Up 
Grade 1 
Asymptomatic or mild symptoms; 
intervention not indicated. 
• Continue AGEN2034 
therapy per protocol. 
• Continue to monitor subject. 
• If worsens: treat as Grade 2 or Grade 
3–4. 
Grade 2 
Moderate symptoms; Limiting 
instrumental activities of daily life 
(ADL). 
• Delay AGEN2034 therapy 
per protocol. 
• Treat symptoms per local 
guidelines. 
• Consider 0.5 to 
1.0 mg/kg/day 
methylprednisolone IV or 
oral equivalent. 
• If returns to baseline: resume 
AGEN2034 therapy per protocol. 
• If worsens: treat as Grade 3-4. 
Grade 3-4 
Severe symptoms; Limiting self- 
care activities of daily life; Life- 
threatening. 
• Discontinue AGEN2034 
therapy per protocol. 
• Obtain neurology consult. 
• Treat symptoms per local 
guidelines. 
• 1.0 to 2.0 mg/kg/day 
methylprednisolone IV or 
IV equivalent. 
• Add prophylactic 
antibiotics for opportunistic 
infections. 
• If improves to Grade 2: taper 
corticosteroids over at least 1month. 
• If worsens or atypical presentation: 
consider IV immunoglobulin or other 
immunosuppressive therapies per local 
guidelines. 
 
  

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6. 
TRIAL ASSESSMENTS AND PROCEDURES 
6.1. 
Phase 1 Schedules of Assessments and Procedures 
The assessments and procedures to be performed in Phase 1 are shown in Table 11 for Part A1 and in Table 12 for PartA2. 
Table 11: 
Phase 1 Part A1 — Schedule of Assessments and Procedures 
Screening 
Treatment Phase (2-week cycles) 
End of Treatment 
Follow-up1 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Visits Schedule (days) 
1 
2 8 
1 
2 8 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m from 
last dose 
6 m from 
last dose 
3 m from 
last visit 
Schedule Window (days) 2 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
≤ 7 
± 7 
± 7 
± 7 
± 7 
Administrative Procedures 
<-42 days 
Informed consent 
X 
Review of inclusion / exclusion criteria 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
Issue Emergency Medical Support and Subject 
Card 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of medical history and demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of baseline symptoms 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
Review of prior and concomitant medications 
X 
X X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Cancer disease details and prior treatment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subsequent antineoplastic therapy status 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
Clinical Procedures / Assessments 
<-7 days 
Review AEs3 
X 
X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examination 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Focused Physical Examination 
 
X  
 
 
 
X 
X 
X 
 
X 
X 
X 
X 
Vital Signs and Weight 
X 
X  
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG4 
X 
X  
 
X 
 
 
X 
 
X 
X 
 
 
 
ECOG Performance Status 
X 
X 
X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Imaging Assessments5 
<-21 days 
Tumor Imaging 
X 
Every 6 weeks (±3 days) from first dose until discontinuation of study drug. 
Brain Imaging 
X 
Continued on next page 

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Screening 
Treatment Phase (2-week cycles) 
End of Treatment 
Follow-up1 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Visits Schedule (days) 
1 
2 8 
1 
2 8 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m from 
last dose 
6 m from 
last dose 
3 m from 
last visit 
Schedule Window (days) 2 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
≤ 7 
± 7 
± 7 
± 7 
± 7 
Central Laboratory Procedures / Assessments6 
<-7 days 
 
Serum for PK and/or ADA Assays 
X7 X8 X 
X7 X8 X 
X9 
X9 
X 
X 
X 
X 
Plasma for Cytokine Assay 
 
X10 X8  
X10 X8  
 
 
 
 
 
 
 
Blood for Biomarkers (whole blood, PBMC, 
serum, and/or plasma) 
X 
X X8 X X 
X8 X 
X 
 
X 
X 
X 
 
 
Local Laboratory Procedures / Assessments11 
<-7 days 
Core serum chemistry12 
X 
X 
X 
X 
Full serum chemistry13 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
Hematology tests14 
X 
 
 
X X 
 
X 
X 
X 
X 
X 
X 
 
 
Coagulation tests15 
X 
 
 
 
X 
 
X 
X 
 
X 
X 
X 
 
 
Endocrine function tests16 
X 
 
 
 
X 
 
X 
X 
 
X 
X 
X 
 
 
Autoimmunity tests17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis18 
X 
 
 
 
X 
 
X 
X 
 
X 
X 
X 
 
 
Serum pregnancy test 
X19 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X19  
 
 
 
 
X 
 
X 
X 
X 
 
 
Study drug administration20 
AGEN2034 
X 
X 
X 
X 
ADA: anti-drug antibody; AEs: adverse events; d: day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; HPV: human papilloma virus; 
m: month; PBMC: peripheral blood mononuclear cell; PK: pharmacokinetics; w: week. 
 
Note: Where applicable, assessments performed prior to treatment unless otherwise indicated. 
 
1  All subjects who discontinue treatment will have at least one Follow-up Visit at 3 months (± 7 days) from last dose of study drug. Subjects who discontinue 
due to disease progression and/or start of a new line of therapy will then end participation in the trial. Subjects who received the maximum administrations of the 
combination of AGEN2034; who have achieved a complete response (CR) according to RECIST 1.1; or who have discontinued treatment due to reasons other 
than disease progression and/or start of a new line of therapy will be in Follow-up for up to approximately 12 months after last dose of study drug or until disease 
progression and/or start of a new line of therapy. Every effort should be made to collect subject information on the start of new antineoplastic therapy, disease 
progression, and death. 
2  Treatment administration and associated procedures for that visit may be delayed for treatment-related AEs beyond the window and subsequent schedule 
adjusted accordingly. 
3  Adverse events will be documented from time of consent until the End-of-Treatment Safety Follow-up Visit, after which only treatment-related AEs will be 
documented through the Follow-up Period of up to 12 months after the last dose of study drug or until disease progression and/or initiation of a new line of 
therapy. DLTs will be assessed during the first 3 weeks of trial treatment for the first 3 subjects at each dose level. 

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4  12-lead ECG on Cycle 1 Day 1, before and 2 hours (-10 / + 20 min) after AGEN2034 administration; on subsequent cycles as indicated 2 hours (-10 / 
+ 20 min) after AGEN2034 infusion or as indicated. 
5  The initial tumor imaging will be performed within 21 days prior to first dose. Scans performed as part of routine clinical management are acceptable for use 
as screening scan if they are of diagnostic quality and < -21 days prior to first dose; and brain MRI if <-21 days prior to first dose. For subjects with no previous 
history of brain metastases, screening brain imaging will need to be obtained; except for subjects with cervical cancer, cutaneous squamous-cell carcinoma, 
gastric/gastroesophageal junction cancer, head and neck squamous-cell carcinoma, ovarian cancer, prostate cancer, mesothelioma, or urothelial carcinoma, for 
whom this scan is necessary only if clinically indicated. MRI is the preferred brain imaging modality; however, CT is acceptable if an MRI is clinically 
contraindicated. On-study imaging will be performed every 6 weeks (+/- 3 days), or more frequently if clinically indicated. Imaging assessments will continue 
until disease progression per the investigator or until a new line of therapy is initiated. The timing of imaging assessments should follow calendar days and 
should not be adjusted for delays in treatment administration or for visits. The same imaging technique should be used in a subject throughout the trial. 
Additional imaging at Discontinuation Visit and Safety Follow-up Visit is not required provided imaging assessments have been performed per schedule. 
6  Unless otherwise specified, samples should be collected before treatment administration. Refer to the Laboratory Manual for instructions and additional 
information. 
7  Before administration of AGEN2034, and 30 (± 15) min, 2 hours (± 15 min), and 4 hours (± 15 min) post-administration of AGEN2034. 
8  At 24 (± 2) hours post-infusion of AGEN2034. 
9  Before and 1 hour (± 15 min) post-administration of AGEN2034. 
10  Before and 4 hours (± 15 min) post-administration of AGEN2034. 
11  For screening, laboratory tests should be performed within 7 days prior to the first dose of trial treatment. Unless otherwise specified, for treatment phase 
visits, laboratory tests may be collected up to 48 hours before visits and results must be available before treatment. 
12  Core serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/total urea, 
calcium, chloride, creatinine, glucose, magnesium, phosphorus/phosphates, potassium, sodium, total bilirubin. Results must be available prior to dosing. 
13  Full serum chemistry: core serum chemistry and albumin, amylase, cholesterol, creatine kinase, C-reactive protein (CRP), gamma glutamyl transferase 
(GGT), lactate dehydrogenase (LDH), lipase, total protein, triglycerides, uric acid. Results must be available prior to dosing. 
14  Hematology tests: absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count (ANC), hematocrit, hemoglobin, mean corpuscular 
hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet count, red blood cell (RBC), white blood 
cell (WBC) and differential count. Results must be available prior to dosing. 
15  Coagulation tests: activated partial thromboplastin time (aPTT), prothrombin time - international normalized ratio (INR). Results must be available prior to 
dosing. 
16  Endocrine function tests: adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH) (if applicable), free thyroxine (T4), thyroid-stimulating 
hormone (TSH). Results must be available prior to dosing. 
17  Autoimmunity tests: anti-nuclear antibody, rheumatoid factor. 
18  Urinalysis including blood, glucose, protein, specific gravity, and microscopic exam if abnormal. Results must be available prior to dosing. 
19  Serum β-human chorionic gonadotropin (β-HCG) pregnancy test for women of child bearing potential at screening within 72 hours of first treatment dose (if 
performed earlier in screening period then a urine pregnancy test may be performed prior to first dose); urine pregnancy test at all other indicated visits (centers 
where urine pregnancy testing is not routine may substitute with serum β-HCG pregnancy test). Results must be available prior to dosing. 
20  AGEN2034 should be administered over 60 minutes (-10/+20 min). Subjects must be observed for 2 hours post-infusion for infusion-related reaction. If 
administration of AGEN2034 is delayed due to an AE, treatment visits may be delayed beyond the window of 3 days and schedules for subsequent visits should 
be adjusted accordingly. 
 
 

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Table 12: 
Phase 1 Part A2 — Schedule of Assessments and Procedures 
Screening 
Treatment Phase (3-week cycles) 
End of Treatment 
Follow-up1 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Visits Schedule (days) 
1 
2 8 15 
1 
2 8 15 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m 
from last 
6 m 
from last 
3 m 
from 
Schedule Window (days) 2 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
± 3 
± 3 
± 7 
± 7 
± 7 
Administrative Procedures 
<-42 days 
Informed consent 
X 
Review of inclusion / exclusion criteria 
X 
X 
Issue Emergency Medical Support and Subject 
Card 
X 
Review of medical history and demographics 
X 
Review of baseline symptoms 
X 
X 
Review of prior and concomitant medications 
X 
X 
X X X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
Cancer disease details and prior treatment 
X 
Subsequent antineoplastic therapy status 
X 
X 
X 
X 
X 
Clinical Procedures / Assessments 
<-7 days 
Review AEs3 
X 
X X X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examination 
X 
X 
Focused Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs and Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG4 
X 
X 
X 
X 
X 
X 
ECOG Performance Status 
X 
X 
X X X 
X 
X X X 
X 
X 
X 
X 
X 
X 
X 
Imaging Assessments5 
<-21 days 
Tumor Imaging 
X 
Every 6 weeks (±3 days) from first dose until discontinuation of study drug. 
Brain Imaging 
X 
Central Laboratory Procedures / Assessments6 
<-7 days 
Serum for PK and/or ADA Assays 
X7 X8 X X X7 X8 X X 
X9 
X9 
X 
X 
X 
X 
Plasma for Cytokine Assay 
X10 X8 
X10 X8 
Blood for Biomarkers (whole blood, PBMC, 
serum, and/or plasma) 
X 
X X8 X X 
X X8 X X 
X 
X 
X 
X 
Continued on next page 

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Screening 
Treatment Phase (3-week cycles) 
End of Treatment 
Follow-up1 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Visits Schedule (days) 
1 
2 8 15 
1 
2 8 15 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m 
from last 
6 m 
from last 
3 m 
from 
Schedule Window (days) 2 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
± 3 
± 3 
± 7 
± 7 
± 7 
Local Laboratory Procedures / Assessments11 
<-7 days 
Core serum chemistry12 
X 
X 
X 
X 
Full serum chemistry13 
X 
X 
X 
X 
Hematology tests14 
X 
X X 
X 
X 
X 
X 
X 
X 
Coagulation tests15 
X 
X 
X 
X 
X 
X 
Endocrine function tests16 
X 
X 
X 
X 
X 
X 
Autoimmunity tests17 
X 
Urinalysis18 
X 
X 
X 
X 
X 
X 
Serum pregnancy test 
X19 
Urine pregnancy test 
X19 
X 
X 
X 
X 
X 
X 
Study drug administration20 
AGEN2034 
X 
X 
X 
X 
Abbreviations: ADA: anti-drug antibody; AEs: Adverse Events; d: day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; HPV: human 
papilloma virus; m: month; PBMC: peripheral blood mononuclear cell; PK: pharmacokinetics; w: week. 
 
Note: Where applicable, assessments performed prior to treatment unless otherwise indicated. 
 
1  All subjects who discontinue treatment will have at least one Follow-up Visit at 3 months (± 7 days) after last dose of study drug. Subjects who discontinue 
due to disease progression and/or start of a new line of therapy will then end participation in the trial. Subjects who received the maximum administrations of the 
combination of AGEN2034; who have achieved a complete response (CR) according to RECIST 1.1; or who have discontinued treatment due to reasons other 
than disease progression and/or start of a new line of therapy will be in Follow-up for up to approximately 12 months after last dose of study drug or until disease 
progression and/or start of a new line of therapy. Every effort should be made to collect subject information on the start of new antineoplastic therapy, disease 
progression, and death. 
2  Treatment administration and associated procedures for that visit may be delayed for treatment-related AEs beyond the window and subsequent schedule 
adjusted accordingly. 
3  Adverse events will be documented from time of consent until the End-of-Treatment Safety Follow-up Visit, after which only treatment-related AEs will be 
documented through the Follow-up Period of up to 12 months after the last dose of study drug or until disease progression and/or initiation of a new line of 
therapy. DLTs will be assessed during the first 3 weeks of trial treatment for the first 3 subjects at each dose level. 
4  12-lead ECG on Cycle 1 Day 1 and 15, before and 2 hours (-10 / + 20 min) after AGEN2034 administration; on subsequent cycles as indicated 2 hours (-10 / 
+ 20 min) after AGEN2034 infusion or as indicated. 
5  The initial tumor imaging will be performed within 21 days prior to first dose. Scans performed as part of routine clinical management are acceptable for use 
as screening scan if they are of diagnostic quality and <-21 days prior to first dose; and brain MRI if <-28 days prior to first dose. For subjects with no previous 
history of brain metastases, screening brain imaging will need to be obtained; except for subjects with cervical cancer, cutaneous squamous-cell carcinoma, 
gastric/gastroesophageal junction cancer, head and neck squamous-cell carcinoma, ovarian cancer, prostate cancer, mesothelioma, or urothelial carcinoma, for 
whom this scan is necessary only if clinically indicated. MRI is the preferred brain imaging modality; however, CT is acceptable if an MRI is clinically 
contraindicated. On-study imaging will be performed every 6 weeks (+/- 3 days), or more frequently if clinically indicated. Imaging assessments will continue 

Agenus, Inc. C-700-01 
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until disease progression per the investigator or until a new line of therapy is initiated. The timing of imaging assessments should follow calendar days and 
should not be adjusted for delays in treatment administration or for visits. The same imaging technique should be used in a subject throughout the trial. 
Additional imaging at Discontinuation Visit and Safety Follow-up Visit is not required provided imaging assessments have been performed per schedule. 
6  Unless otherwise specified, samples should be collected before treatment administration. Refer to the Laboratory Manual for instructions and additional 
information. 
7  Before administration of AGEN2034, and 30 (± 15) minutes, 2 hours (± 15 min), and 4 hours (± 15 min) post-administration of AGEN2034. 
8  At 24 (± 2) hours post-infusion of AGEN2034. 
9  Before and 1 hour (± 15 min) post-administration of AGEN2034. 
10  Before and 4 hours (± 15 min) post-administration of AGEN2034. 
11  For screening, laboratory tests should be performed within 7 days prior to the first dose of trial treatment. Unless otherwise specified, for treatment phase 
visits, laboratory tests may be collected up to 48 hours before visits and results must be available before treatment. 
12  Core serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/total urea, 
calcium, chloride, creatinine, glucose, magnesium, phosphorus/phosphates, potassium, sodium, total bilirubin. Results must be available prior to dosing. 
13  Full serum chemistry: core serum chemistry and albumin, amylase, cholesterol, creatine kinase, C-reactive protein (CRP), gamma glutamyl transferase 
(GGT), lactate dehydrogenase (LDH), lipase, total protein, triglycerides, uric acid. Results must be available prior to dosing. 
14  Hematology tests: absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count (ANC), hematocrit, hemoglobin, mean corpuscular 
hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet count, red blood cell (RBC), white blood 
cell (WBC) and differential count. Results must be available prior to dosing. 
15  Coagulation tests: activated partial thromboplastin time (aPTT), prothrombin time - international normalized ratio (INR). Results must be available prior to 
dosing. 
16  Endocrine function tests: adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH) (if applicable), free thyroxine (T4), thyroid-stimulating 
hormone (TSH). Results must be available prior to dosing. 
17  Autoimmunity tests: anti-nuclear antibody, rheumatoid factor. 
18  Urinalysis including blood, glucose, protein, specific gravity, and microscopic exam if abnormal. Results must be available prior to dosing. 
19  Serum β-human chorionic gonadotropin (β-HCG) pregnancy test for women of child bearing potential at screening within 72 hours of first treatment dose (if 
performed earlier in screening period then a urine pregnancy test may be performed prior to first dose); urine pregnancy test at all other indicated visits (centers 
where urine pregnancy testing is not routine may substitute with serum β-HCG pregnancy test). Results must be available prior to dosing. 
20  AGEN2034 should be administered over 60 minutes (-10/+20 min). Subjects must be observed for 2 hours post-infusion for infusion-related reaction. If 
administration of AGEN2034 is delayed due to an AE, treatment visits may be delayed beyond the window of 3 days and schedules for subsequent visits should 
be adjusted accordingly. 

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6.2. 
Phase 2 Schedule of Assessments and Procedures 
The assessments and procedures for Phase 2 are summarized in Table 13 for PK, ADA, 
biomarkers, and pharmacogenomics assessments are shown in Table 14. 
 
 

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Table 13: 
Phase 2 — Schedule of Assessments and Procedures 
Screening 
Treatment Phase (2-week cycles) 
End of Treatment 
Follow Up1 
Survival 
Follow 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Telephone 
Visits Schedule (days) 
1 
2 8 
1 
2 8 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m 
from last 
6 m 
from last 
3 m from
last visit 
Every 2 
months 
Schedule Window (days) 3 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
≤ 7 
± 7 
± 7 
± 7 
± 7 
Administrative Procedures 
< -42 days 
Informed consent 
X 
Review of inclusion / exclusion criteria 
X 
X 
Issue Emergency Medical Support and Subject Card 
X 
Review of medical history and demographics 
X 
Review of baseline symptoms 
X 
X 
Review of prior and concomitant medications 
X 
X X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Cancer disease details and prior treatment 
X 
Subsequent antineoplastic therapy status 
X 
X 
X 
X 
X 
X 
Survival status 
X 
Clinical Procedures / Assessments 
< -7 days 
Review AEs5 
X 
X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examination 
X 
X 
Focused Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs and Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG6 
X 
X 
X 
X 
X 
X 
X 
X 
Expanded ECG Evaluation6a 
 
X 
X  
 
 
 
 
See 6a 
 
 
 
 
 
ECOG Performance Status 
X 
X 
X X X 
X X 
X 
X 
X 
X 
X 
X 
X 
Biopsy & Imaging Assessments 
< -21days 
Tumor Biopsy 4 
X 
See 4 
Tumor Imaging7 
X 
Every 6 weeks (± 3 days) from first dose until discontinuation of study drug  
Brain Imaging8 
X 
Blood Samples for PK, ADA, Biomarkers, and 
 
See Table 14and Laboratory Manual 
Continued on next page 

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Screening 
Treatment Phase (2-week cycles) 
End of Treatment 
Follow Up1 
Survival 
Follow 
Cycle 1 
Cycle 2 
Every 
Subsequent 
Odd Cycle 
Every 
Subsequent 
Even Cycle 
Discontinuation 
Visit 
Safety 
Visit 
Visit 1 
Visit 2 
Visits 3 
and 4 
Telephone 
Visits Schedule (days) 
1 
2 8 
1 
2 8 
1 
1 
At 
Discontinuation 
4 w from 
last dose 
3 m 
from last 
6 m 
from last 
3 m from
last visit 
Every 2 
months 
Schedule Window (days) 3 
−3/+1 
−3/+1 
−3/+1 
−3/+1 
≤ 7 
± 7 
± 7 
± 7 
± 7 
Local Laboratory Procedures / Assessments14 
< -7 days 
Core serum chemistry15 
X 
X 
X 
Full serum chemistry16 
X 
 
  
 
  
 
 
X 
X 
X 
 
 
 
Hematology tests17 
X 
 
 X X 
  
X 
X 
X 
X 
X 
 
 
 
Coagulation tests18 
X 
 
  
X 
  
X 
 
X 
X 
X 
 
 
 
Endocrine function tests19 
X 
 
  
X 
  
X 
 
X 
X 
X 
 
 
 
Urinalysis21 
X 
 
  
X 
  
X 
 
X 
X 
X 
 
 
 
Serum pregnancy test 
X22 
 
  
 
  
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X22   
 
  
X 
 
X 
X 
X 
 
 
 
Study drug administration23 
AGEN2034 
 
X 
  
X 
  
X 
X 
 
 
 
 
 
 
Abbreviations: ADA: anti-drug antibody; AEs: Adverse Events; d: day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; IERC: Independent Endpoint 
Review Committee; m: month; PBMC: peripheral blood mononuclear cell; PGx: pharmacogenomics; PK: pharmacokinetics; w: week. 
 
Note: Where applicable, assessments performed prior to treatment unless otherwise indicated. 
 
1  All subjects who discontinue treatment will have at least one Follow-up Visit at 3 months (± 7 days) after last dose of study drug. Subjects who discontinue due to disease 
progression and/or start of a new line of therapy will then end participation in the trial. Subjects who received the maximum administrations of the combination of AGEN2034; 
who have achieved a complete response (CR) according to RECIST 1.1; or who have discontinued treatment due to reasons other than disease progression and/or start of a new 
line of therapy will be in Follow-up for up to approximately 12 months after last dose of study drug or until disease progression and/or start of a new line of therapy. Every effort 
should be made to collect subject information on the start of new antineoplastic therapy, disease progression and death. 
2  After the first Follow-up Visit, subjects that present(ed) with progressive disease and/or start new line of therapy will move into Survival Follow-up and should be contacted by 
telephone every 2 months for up to 12 months after last dose of study drug to assess for survival status. Post-study treatments and the subject’s response to them will also be 
collected. 
3  Treatment administration and associated procedures for that visit may be delayed for treatment related AEs beyond the window and subsequent schedule adjusted accordingly. 
4  Tumor tissue for biomarker analysis from a biopsy of a tumor lesion not previously irradiated must be available for PD-L1 expression and HPV evaluation. Only biopsies 
obtained at the time of or after the diagnosis of metastatic disease will be evaluated for PD-L1 expression. If a tumor biopsy was obtained from a target lesion during eligibility 
assessment, it is preferred to obtain a new baseline scan. Biopsy of lesions on study should be limited to non-target lesions or new lesions if their pathologic etiology is ambiguous. 
FOR SUBSEQUENT EVEN CYCLES: An optional biopsy is desired at Cycle 4 ONLY and, if provided, should be collected on Day 1 before AGEN2034 administration. 
5  Adverse events will be documented from time of consent up until 90 days after the last dose of study drug or the start of a new anticancer treatment, whichever comes first. 
Following the End-of-Treatment Safety Follow-up Visit, only treatment-related AEs will be documented through the Treatment Follow-up Period of up to 12 months after the last 
dose of study drug or until disease progression and/or initiation of a new line of therapy. 
6 
12-lead ECG on Cycle 1 Day 1, before AGEN2034 infusion starts and 2 hours (-10/+ 20 min) after infusion ends; on subsequent cycles as indicated 1 hour (-10 / + 20 min) 
after infusion ends or at visits indicated. 

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6a  (At selected sites only) Expanded ECG Evaluation (triplicate tracings; see Section 6.4.3.4): 12-lead ECGs will be taken for Cycles 1 and 4 on Day 1 within 15 min (± 10 min) 
before the Predose PK sample and within 15 min (± 10 min) before the 30-min-after-end-of-infusion PK sample, and on Day 2 within 15 min (± 10 min) before the 24-h-after-end-
of-infusion PK sample. ECGs (12-lead, triplicate tracings) will also be taken for every subsequent 8th cycle for up to 1 year (approximately every 4 mo [in Cycles 12, 20, and 28]) 
on Day 1 within 15 min (± 10 min) before the Predose PK sample and within 15 min (± 10 min) before the 30-min-after-end-of-infusion PK sample. 
7  The initial tumor imaging will be performed within 21 days prior to first dose. Scans performed as part of routine clinical management are acceptable for use as screening scan 
if they are of diagnostic quality and < 21 days prior to first dose. On-study imaging will be performed every 6 weeks (± 3 days), or more frequently if clinically indicated, and 
submitted for central review. Tumor assessments should be performed every 6 weeks (± 3 days) from first treatment dose until RECIST 1.1-defined disease progression has been 
established by the blinded independent central radiology review. Furthermore, if study drug is discontinued as a result of unacceptable toxicity, tumor assessments should continue 
every 6 weeks (± 3 days) until RECIST1.1-defined disease progression has been established by the blinded independent central radiology review. Imaging is required every 
6 weeks (± 3 days) for those subjects with  PD who remain on AGEN2034 per protocol exemption (Section 5.4.5) until treatment is discontinued. 
8  Screening brain imaging is only necessary if clinically indicated. MRI is the preferred brain imaging modality; however, CT is acceptable if an MRI is clinically 
contraindicated. 
9-13  Removed. 
14  For screening, laboratory tests should be performed within 7 days prior to the first dose of trial treatment. Unless otherwise specified, for treatment phase visits, laboratory tests 
may be collected up to 48 hours before visits and results must be available before treatment. 
15  Core serum chemistry: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN)/total urea, calcium, chloride, 
creatinine, glucose, magnesium, phosphorus/phosphates, potassium, sodium, total bilirubin. Results must be available prior to dosing. 
16  Full serum chemistry: core serum chemistry and albumin, amylase, cholesterol, creatine kinase, C-reactive protein (CRP), gamma glutamyl transferase (GGT), lactate 
dehydrogenase (LDH), lipase, total protein, triglycerides, uric acid. Results must be available prior to dosing. 
17  Hematology Tests: absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count (ANC), hematocrit, hemoglobin, mean corpuscular hemoglobin (MCH), 
mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet count, red blood cell (RBC), white blood cell (WBC) and differential count. 
Results must be available prior to dosing. 
18  Coagulation Tests: activated partial thromboplastin time (aPTT), prothrombin time - international normalized ratio (INR). Results must be available prior to dosing. 
19  Endocrine function tests: adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH) (for postmenopausal women if applicable), free thyroxine (T4), thyroid-
stimulating hormone (TSH). Results must be available prior to dosing. 
20  Removed. 
21  Urinalysis including blood, glucose, protein, specific gravity, and microscopic exam if abnormal. Results must be available prior to dosing. 
22  Serum β-human chorionic gonadotropin (β-HCG) pregnancy test for women of child bearing potential at screening within 72 hours of first treatment dose (if performed earlier 
in screening period then a urine pregnancy test may be performed prior to first dose); urine pregnancy test at all other indicated visits. Results must be available prior to dosing. 
23  AGEN2034 should be administered over 60 min (-10/+20 min). For the first 2 cycles, subjects must be observed for 2 hours post-infusion for infusion-related reaction; for 
subsequent cycles subjects must be observed for at least 1 hour post-infusion for infusion-related reaction. If administration of AGEN2034 is delayed due to an AE, treatment visits 
may be delayed beyond the window of 3 days and schedules for subsequent visits should be adjusted accordingly. 
 
 

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Table 14: 
Phase 2 — Blood Sampling for Pharmacokinetic, Pharmacodynamic, Genetic, and Other Assessments 
Visit or Cycle 
Day 
For PK  
(see NOTE) 
Additional Time 
Points for Rich 
PK Subset 
For ADA 
For PBMC 
For 
 
For PGx 
Screening 
— 
— 
— 
— 
— 
— 
X1 
Cycle 1 
1 
Predose2 
30 min (± 15 
min)3 
— 
Predose2 
Predose2 
Predose2 
— 
2 
— 
24 h (± 60 min)4 
— 
— 
— 
— 
8 
— 
168 h (± 4 h)4 
— 
— 
— 
— 
Cycle 2 
1 
Predose2 
— 
Predose2 
Predose2 
Predose2 
— 
Cycle 3 
1 
Predose2 
— 
Predose2 
Predose2 
— 
— 
Cycle 4 
1 
Predose2 
30 min (± 15 
min)3 
— 
Predose2 
Predose2 
Predose2 
— 
2 
— 
24 h (± 60 min)4 
— 
— 
— 
— 
8 
— 
168 h (± 4 h)4 
— 
— 
— 
— 
Cycles 5, 6, 12, 18, 24 
1 
— 
— 
Predose2 
— 
— 
— 
Discontinuation 
— 
X  
— 
X 
X 
X 
— 
Safety Follow-up Visit 
4 wk after last dose
X 
— 
X 
— 
— 
— 
Follow-up Visit 
3 mo after last dose
X 
— 
X 
— 
— 
— 
Abbreviations: ADA: antidrug antibody; 
 DNA: deoxyribonucleic acid; h: hour(s); mo: month; min: minute(s); PBMC: 
peripheral blood mononuclear cell; PGx: pharmacogenomics(s); PK: pharmacokinetic(s); wk: week(s).  
1 
Blood sample for PGx is collected only if an ‘optional’ PGx consent is signed. 
2 Predose samples will be collected within 30 minutes before starting the AGEN2034 infusion. 
3 Blood samples collected on Day 1 at 30 (± 15) minutes after the end of infusion  
4 
As of Amendment 5 (27 September 2019), additional rich PK sampling will be collected in a subset of approximately 20 subjects in selected sites. Rich PK 
sampling will occur on Days 2 and 8 of Cycles 1 and 4  at 24 hours (± 60 min) and 168 (± 4) hours, respectively, after the start of the infusion. 
NOTE: It is important to record all infusion start dates/times, infusion end dates/times, infusion interruption(s) start and end dates/times, infusion flush end 
dates/times, and blood sample dates/times completely and accurately (to the nearest minute). Blood for the 30-minute postdose PK samples should never be 
taken during the infusion and should be drawn at least 15 min after the end of infusion. 
 

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6.3. 
Visit Requirements 
6.3.1. 
Screening 
Visit requirements are outlined for Phase 1 in Section 6.1 and for Phase 2 in Section 6.2. Specific 
procedure-related details are provided in Section 6.4. 
6.3.2. 
Treatment Phase 
Visit requirements are outlined for Phase 1 in Section 6.1 and for Phase 2 in Section 6.2. Specific 
procedure-related details are provided in Section 6.4. 
Subject should continue to receive all assessments as defined in the Treatment phase of the 
Schedule of Assessments while they are actively receiving treatment. 
6.3.3. 
End-of-Treatment Visits 
Visit requirements are outlined for Phase 1 in Section 6.1 and for Phase 2 in Section 6.2. Specific 
procedure-related details are provided in Section 6.4. 
6.3.3.1. 
Discontinuation Visit 
The Discontinuation Visit should occur at the time study drug is discontinued for any reason. If 
the Discontinuation Visit occurs 4 weeks from the last dose of study drug, at the time of the 
mandatory Safety Follow up Visit, procedures do not need to be repeated. Procedures at the time 
of discontinuation are detailed in Section 6.3.3.2, Safety Follow up Visit. 
6.3.3.2. 
Safety Follow-up Visit 
The mandatory Safety Follow-Up Visit should be conducted for all subjects approximately 
4 weeks after the last dose of study drug or before the initiation of a new antineoplastic 
treatment, whichever comes first. Subjects with an AE of Grade >1 will be further followed until 
the resolution of the AE to Grade 0-1 or until beginning of a new antineoplastic therapy, 
whichever occurs first. Subjects with an adverse drug reaction (ADR) ongoing at the Safety 
Follow-up Visit must be followed up until the ADR resolves, becomes stable, or is considered 
not clinically significant by the investigator. 
6.3.4. 
Follow-up Phase 
In Phase 1, subjects who discontinue treatment will be followed for up to 12 months after the last 
dose of study drug or until death, withdrawal of consent, or becoming lost to follow-up.  
In Phase 2, subjects who discontinue treatment will be followed for up to 24 months after the last 
dose of study drug or until death, withdrawal of consent, or becoming lost to follow-up. 
Follow-up visits and survival follow-up requirements are outlined in Section 6.1 and Section 6.2, 
respectively, for Phase 1 and Phase 2. Specific procedure-related details are provided in 
Section 6.4. 
 

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6.3.4.1. 
Follow-up Visits 
All subjects who discontinue treatment will have at least one post-treatment visit at 3 months 
(± 7 days) after last dose of study drug.  
For both study Phases, subjects who received the maximum administrations of AGEN2034, who 
have achieved a complete response (CR) according to RECIST 1.1, or who have discontinued 
treatment due to reasons other than disease progression and/or start of a new line of therapy 
should be have Follow-up Visits every 3 months for up to 12 months after last dose of study drug 
(see schedules in Section 6.1) or until disease progression and/or start of a new line of therapy. 
For Phase 2 (see schedule in Section 6.2), subjects who present with progressive disease and/or 
start a new line of therapy will move into the Survival Follow-up Phase. Every effort should be 
made to collect subject information on the start of new antineoplastic therapy, disease 
progression and death.  
6.3.4.2. 
Survival Follow-up (Phase 2 only) 
There is no survival follow-up for Phase 1. 
For subjects in Phase 2, after the first Treatment Follow-up Visit, subjects with progressive 
disease and/or who start new line of therapy will move into Survival Follow-up. Subjects should 
be contacted by telephone to assess for survival status every 2 months for up to 12 months after 
their last dose of study drug. 
6.4. 
Trial Procedures 
The schedules of events in Section 6.1 and Section 6.2 summarize the trial procedures to be 
performed at each visit in Phase 1 and 2, respectively. Individual trial procedures are described 
in detail below. It may be necessary to perform these procedures at unscheduled time points if 
deemed clinically necessary by the investigator. 
Furthermore, additional evaluations/testing may be deemed necessary by the investigator and or 
the Sponsor for reasons related to subject safety. In these cases, such evaluations/testing will be 
performed in accordance with clinical judgement.  
6.4.1. 
Administrative Procedures 
6.4.1.1. 
Informed Consent 
The investigator or qualified designee must obtain documented consent from each potential 
subject prior to participating in the clinical trial and for optional pharmacogenomics research. 
6.4.1.2. 
General Informed Consent 
Consent must be documented by the subject’s dated signature along with the dated signature of 
the person conducting the consent discussion. A copy of the signed and dated consent form 
should be given to the subject before participation in the trial. 
The investigator is responsible for ensuring that a careful and thorough informed consent 
procedure is implemented before a subject enters the study and at any time during the study 
should ICF changes be introduced. This includes, but is not limited to: (1) allowing ample time 

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for this review by the subject; (2) ensuring that qualified medical personnel are available to 
directly answer questions that a subject may have; (3) ensuring that each potential study subject 
understands that his or her medical treatment will not be otherwise affected based on the decision 
whether or not to participate in the study, that his or her participation is completely voluntary, 
and that he or she can opt to stop participation in the study at any time for any reason; and (4) 
ensuring a full copy of the signed ICF is given to the subject to take home for his or her medical 
records. The process for obtaining informed consent should also be noted in the subject’s source 
documentation. 
The initial informed consent form, any subsequent revised written informed consent form, and 
any written information provided to the subject must receive the IRB/ERC’s approval/favorable 
opinion in advance of use. The subject should be informed in a timely manner if new information 
becomes available that may be relevant to the subject’s willingness to continue participation in 
the trial. The communication of this information will be provided and documented via a revised 
consent form or addendum to the original consent form that captures the subject’s dated 
signature or by the subject’s legally acceptable representative’s dated signature. 
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations and 
Sponsor requirements. 
6.4.1.3. 
Consent for Pharmacogenomics Assessment (optional) 
Participation in the pharmacogenomics portion of the trial is optional and requires separate 
informed consent. Participation in the pharmacogenomics portion of the trial will not affect 
participation in the trial. Subjects may withdraw consent from pharmacogenomics portion of the 
trial without withdrawing from the trial. 
Specimens that may be used for pharmacogenomics testing include: blood and tumor specimens 
collected during this trial. 
The investigator or qualified designee will explain the optional pharmacogenomics assessment 
portion of the consent to the subject, answer all of his/her questions, and obtain written informed 
consent before performing any procedure related to pharmacogenomics assessment. A copy of 
the informed consent will be given to the subject. 
6.4.1.4. 
Review of Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee to 
ensure that the subject qualifies for the trial. 
6.4.1.5. 
Emergency Medical Support and Subject Card 
All subjects will be given an Emergency Medical Support and Subject Card identifying them as 
participants in a research trial. The card will contain trial site contact information (including 
direct telephone numbers) to be utilized in the event of an emergency. The investigator or 
qualified designee will provide the subject with an Emergency Medical Support and Subject 
Card immediately after the subject provides written informed consent. 

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6.4.1.6. 
Medical History 
A medical history will be obtained by the investigator or qualified designee. Medical history will 
include all active conditions; history of hepatitis B virus (HBV), hepatitis C virus (HCV), HIV 
and/or HPV; and any condition diagnosed within the prior 10 years that are considered to be 
clinically significant by the Investigator. Medical history will also include an assessment of 
smoking history.  
History of the cancer under study will be recorded separately (see Section 6.4.1.9); all other 
cancer history should be captured in the medical history. 
For subjects in Phase 2, in addition, record any prior cancer other than cervical cancer even if 
diagnosed greater than 10 years prior to Visit 1.  
6.4.1.7. 
Review of Baseline Symptoms 
Baseline symptoms associated with the disease under study will be assessed for each subject at 
screening. Baseline symptoms will be Graded and recorded according to NCI CTCAE 
Version 4.03. Baseline symptoms will be characterized in terms including seriousness, causality 
to previous treatment, toxicity grading, and action(s) taken if any. 
6.4.1.8. 
Review of Prior and Concomitant Medications 
6.4.1.8.1. Prior Medications 
All medication — other than chemotherapy — taken by the subject within 30 days before 
starting the trial will be recorded. In addition, all treatments for a prior cancer other than current 
cancer will be recorded, even if taken greater than 30 days prior to Visit 1.  
Prior treatments for the current cancer will be recorded separately (see Section 6.4.1.9) and not 
listed as a prior medication. 
6.4.1.8.2. Concomitant Medications 
Any medication taken by the subject during the trial, from the date of consent through the 30-day 
Safety Follow-up Visit, will be recorded. After the Safety Follow-up Visit, record all 
medications related to reportable SAEs and AESIs as defined in Section 7.2.2.2. 
6.4.1.9. 
Cancer Disease Details and Prior Treatment 
Obtain current cancer disease details and prior treatment for all subjects including: 
• Detailed history of the tumor at diagnosis and study entry including histopathological 
diagnosis, grading, and staging in accordance with the AJCC-8 Tumor Node 
Metastasis (TNM) classification (Amin et al 2017). 
• All therapy used for prior treatment of the disease under study (including but not 
limited to surgery, radiotherapy [including total radiation dose received and general 
treatment field], and any systemic treatment) – and for each therapy, complete dosing 
schedule and their corresponding best response. 
• Any other conditions treated with radiation therapy or and any systemic treatment. 

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• Current cancer signs and symptoms, and side effects from current and/or previous 
anticancer treatments. 
• Current cancer disease status. 
• Relevant somatic or germline mutations detected. 
• Chronic viral infection status, if available. 
• Human epidermal growth factor receptor 2 (HER2) status, if available. 
• Smoking history. 
• Tumor markers, including but not limited to, molecular/genetic or 
immunohistochemistry markers (such as PSA, CA125, AFP, BRCA, PD-L1 status, 
etc.), if applicable and available. 
• HPV status, if available. 
6.4.1.9.1. Subsequent Antineoplastic Therapy 
The investigator or qualified designee will review all new antineoplastic therapy initiated after 
the last dose of study drug. If a subject initiates a new antineoplastic therapy within 4 weeks after 
the last dose of study drug, the Safety Follow-up Visit must occur before the first dose of the 
new therapy.  
Subjects in Phase 2 will move into survival follow-up once new antineoplastic therapy has been 
initiated. 
6.4.1.9.2. Survival Follow-up (Phase 2 only) 
Once a subject in Phase 2 moves into the survival follow-up period, they should be contacted by 
telephone every 2 months for up to 12 months after their last dose of study drug. (See also 
Section 6.3.4.2.) 
6.4.1.10. Assignment of Subject Trial Number 
After a subject signs an informed consent form, the subject will be assigned a unique, sequential 
subject number. Once a number is assigned, it cannot be reassigned if the original subject is 
found to be ineligible or withdraws consent. 
6.4.1.11. Trial Compliance 
Any delay from the protocol-specified AGEN2034 dosing frequency which is due to toxicity and 
which results in > 6 weeks between AGEN2034 doses requires consultation between the 
investigator and the Sponsor, and written documentation of the collaborative decision on subject 
management. 
Administration of trial medication will be witnessed by the investigator and/or trial staff. The 
total volume of trial treatment infused will be compared to the total volume prepared to 
determine compliance with each dose administered. 
Any reason for noncompliance should be documented. Noncompliance is defined as a subject 
missing >1 cycle of study treatment for non-medical reasons. If 1 cycle was missed and the 

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interval between the subsequent treatment cycle and the last administered treatment cycle is 
longer than 4 weeks for non-medical reasons, criteria for insufficient compliance are met. 
6.4.2. 
Tissue Collection and Tumor Biomarker Assessment 
For Phase 2, expression of PD-L1 and HPV status will be among the exploratory biomarkers 
assessed in tumor samples from archival tissues or biopsies. 
6.4.2.1. 
Tissue Collection 
Tumor tissue for biomarker analysis from a biopsy of a tumor lesion not previously irradiated 
must be available for biomarker assessments including but not limited to PD-L1 expression and 
HPV evaluation. Biomarker assessment will be performed on the most recent FFPE biopsy of a 
tumor lesion, collected either at the time of or after the diagnosis of metastatic disease has been 
made, and from a site not previously irradiated. An optional tumor biopsy will be collected at 
Cycle 4, Day 1 (-3/+1 day) if clinically feasible to assess pharmacodynamic effects of the drug 
on tumor microenvironment. 
• Tissue from needle or excisional biopsy or from resection is required. 
• An FFPE tumor tissue block that is less than 4 years old should be provided. If an 
archival tumor-containing FFPE tissue block is not available, freshly cut FFPE slides 
(within 10 days) are acceptable for submission to the sponsor. If an FFPE tumor 
tissue block or freshly cut slides are not available, fresh biopsy will be required, and 
an FFPE tumor tissue block should be provided. If a block or freshly cut FFPE slides 
are not available, discuss with the study Medical Monitor prior to patient enrollment. 
• Fine needle aspirates, endobronchial ultrasound (EBUS), or cell blocks are not 
acceptable. 
If limited tissue is available, preference will be given to PD-L1 assessment. 
If a tumor biopsy was obtained from a target lesion during eligibility assessment, it is preferred 
to obtain a new baseline scan. Biopsy of lesions on study should be limited to non-target lesions 
or new lesions if their pathologic etiology is ambiguous.  
Tissue processing: The cancer tissues should be fixed in 10% neutral buffered formalin, paraffin 
embedded, and routinely processed for histological evaluation. Formalin substitutes are not 
suited as fixative.  
Provision of samples:  
1. Priority: tumor-containing FFPE tissue block that is less than 4 years old 
2. If an archival tumor-containing FFPE tissue block is not available, a fresh biopsy will be 
required, and an FFPE tumor tissue block should be provided. 
3. Priority: 25 freshly cut tumor tissue FFPE slides (within 10 days) must be provided. 
Minimum 15 slides are required. The FFPE slides must be freshly cut and submitted to 
the sponsor within 10 days from the slide sectioning date. All submitted slides must be 
cut from a single tumor tissue sample specimen. The site must ensure that the newly 
obtained tissue sample collection data and slide cut date are documented in the 

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requisition forms. Slides submitted more than 10 days after cutting or cut from more than 
one tissue specimen block will be rejected, and a new specimen will be required. 
Sample shipment: The tumor blocks should be sent with the next scheduled monthly shipment to 
the central lab at room temperature. 
Sample storage: At the central laboratory, the FFPE tissue blocks shall be stored at room 
temperature in the dark and the FFPE tumor block shall be kept in sealed containers at 2°C to 
8°C. 
For additional details and instructions regarding tissue requirements, collection, storage and 
shipment, refer to the study Laboratory Manual. 
6.4.2.2. 
PD-L1 Expression Assessment 
Tumor expression of PD-L1 will be assessed using an FDA-approved test in all subjects in 
Phase 2. 
6.4.2.3. 
HPV Assessment 
For subjects with cervical cancer (Phase 2), tissue sample provided at screening will be used for 
HPV assessment. Should tissue only be sufficient for PD-L1 expression assessment, the subject 
may still be enrolled and HPV status will not be assessed. 
6.4.3. 
Clinical Assessments and Procedures 
6.4.3.1. 
Review of Adverse Events 
The investigator or qualified designee will assess each subject to evaluate for potential new or 
worsening AEs as specified in the Schedule of Assessments and Procedures and more frequently 
if clinically indicated. Adverse experiences will be Graded and recorded throughout the study 
and during the follow-up period according to NCI CTCAE Version 4.03 (see Section 7). 
Toxicities will be characterized in terms including seriousness, causality, toxicity grading, and 
action taken with regard to trial treatment. 
Comprehensive assessment of any AE experienced by the subject will be performed throughout 
the course of the trial, from time of the subject’s consent. Trial site personnel will report any AE, 
whether observed by the investigator or reported by the subject (Section 7.2). Given the intended 
mechanism of action, particular attention should be given to AEs that may result from enhanced 
T-cell activation, such as dermatitis, colitis, hepatitis, uveitis, or other immune-related reactions. 
When clinically indicated, ophthalmologic examinations should be considered for signs or 
symptoms of uveitis. 
An irAE may be defined as an AE of unknown etiology, associated with drug exposure and is 
consistent with an immune phenomenon. Efforts should be made to rule out neoplastic, 
infectious, metabolic, toxin or other etiologic causes prior to labeling an AE immune related. 
Immunological, serological and histological (biopsy) data should be used to support the 
diagnosis of an immune-related toxicity. Following the guidance described in Section 7.2.2.2, 
certain irAEs should also be reported to the Sponsor as AESIs. 
The reporting period for AEs is described in Section 7.2.1. 

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6.4.3.2. 
Physical Examination 
6.4.3.2.1. Full Physical Examination 
The investigator or qualified designee will perform a complete physical exam during the 
screening period, as per Section 6.1 (Phase 1) or Section 6.2 (Phase 2). Clinically significant 
abnormal findings should be recorded as medical history. After consent, new clinically 
significant abnormal findings should be recorded as AEs. 
6.4.3.2.2. Focused Physical Examination 
For cycles that do not required a full physical exam per Section 6.1 (Phase 1) or Section 6.2 
(Phase 2), the investigator or qualified designee will perform a directed physical exam as 
clinically indicated prior to trial treatment administration. New clinically significant abnormal 
findings should be recorded as AEs. 
6.4.3.3. 
Vital Signs, Height and Weight 
Vital signs, height, and weight will be measured and recorded as specified in Section 6.1 
(Phase 1, Table 11 or Table 12) or Section 6.2 (Phase 2, Table 13). The investigator or qualified 
designee will take vital signs at the specified times including prior to the administration of each 
dose of trial treatment. Vital signs include temperature, pulse, respiratory rate, and blood 
pressure. Weight should be measured prior to dosing. Height will be measured at Visit 1 only. 
6.4.3.4. 
12-lead Electrocardiogram 
A standard 12-lead ECG will be performed using local standard procedures at screening and as 
specified in Section 6.1 (Phase 1, Table 11 or Table 12) or Section 6.2 (Phase 2, Table 13). 
Clinically significant abnormal findings at Screening should be recorded as medical history. 
6.4.3.5. 
Expanded Electrocardiogram Evaluation (in selected sites only) 
In Phase 2, in addition to the standard 12-lead ECGs, expanded ECG evaluation will occur with 
12-lead ECG tracings recorded in triplicate at selected sites only and on the following schedule 
(see also Table 13): 
• Cycles 1 and 4: 
− On Day 1 (day of infusion), within 15 min (± 10 min) before the Predose PK 
sample and within 15 min (± 10 min) before the 30-min-after-end-of-infusion PK 
sample 
− On Day 2, within 15 min (± 10 min) before 24-h-after-end-of-infusion PK sample 
• Every subsequent 8th cycle (that is, approximately every 4 months for up to 1 year, in 
Cycles 12, 20, and 28): 
− On Day 1 (day of infusion), within 15 min (± 10 min) before the Predose PK 
sample and within 15 min (± 10 min) before the 30-min-after-end-of-infusion PK 
sample 
Every attempt should be made to use the same ECG machine for all measurements within a 
subject, and ECG values should be computer-generated. 

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6.4.3.6. 
Eastern Cooperative Oncology Group Performance 
ECOG status will be assessed (see Appendix II) at screening, prior to the administration of each 
dose of trial treatment and during the Follow-up period as specified in Section 6.1 (Phase 1) or 
Section 6.2 (Phase 2). 
6.4.4. 
Imaging Assessments 
6.4.4.1. 
Tumor Imaging 
In Phase 1, the initial tumor imaging will be performed within 21 days prior to first dose; 
however, scans performed as part of routine clinical management are acceptable for use as 
screening scan if they are of diagnostic quality and performed < 21 days prior to first dose. On-
study imaging will be performed every 6 weeks (± 3 days) from first treatment dose (or more 
frequently if clinically indicated) until discontinuation of study drug.  
In Phase 2, the initial tumor imaging will be performed within 21 days prior to first dose; 
however, scans performed as part of routine clinical management are acceptable for use as 
screening scan if they are of diagnostic quality and performed < 21 days prior to first dose. All 
subjects must have an independent central radiologic review to confirm measurable disease by 
RECIST 1.1 prior to first dose. Subjects without centrally confirmed measurable disease at 
baseline will not be eligible for this trial. On-study imaging will be performed every 6 weeks (± 
3 days) from first dose (or more frequently if clinically indicated) until discontinuation of study 
drug. Imaging studies will be submitted for central review by the IERC.   
The timing of on-study-treatment imaging should follow calendar days and should not be 
adjusted for delays in treatment administration or for visits. Additional imaging at the 
Discontinuation Visit and Safety Follow-up Visit is not required provided imaging assessments 
have been performed per schedule. 
Throughout the trial, the same imaging technique should be used in a subject. In general, lesions 
detected at baseline should be followed using the same imaging methodology and preferably the 
same imaging equipment at subsequent tumor evaluation visits. The investigator may perform 
scans in addition to a scheduled trial scan for medical reasons or if progressive disease is 
suspected. 
6.4.4.2. 
Brain Imaging 
MRI is the preferred brain imaging modality; however, CT is acceptable if an MRI is clinically 
contraindicated. 
In Phase 1, subjects with no previous history of brain metastases are required to have brain 
imaging at screening (within 21 days from prior to first treatment dose) unless adequate imaging 
is available for exams within 21 days prior to the first dose of trial treatment; except for subjects 
with cervical cancer, cutaneous squamous-cell carcinoma, gastric/gastroesophageal junction 
cancer, head and neck squamous-cell carcinoma, ovarian cancer, prostate cancer, mesothelioma, 
or urothelial carcinoma, for whom brain imaging is necessary only if clinically indicated. 
In Phase 2, brain imaging should only be conducted if clinically indicated. 

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During the trial, brain CT/MRI (with contrast if not contraindicated) scans should be conducted 
if clinically indicated by development of new specific symptoms. 
6.4.4.3. 
Response Assessment 
Response assessment will be done according to RECIST 1.1 (Eisenhauer et al 2009) in Phase 1 
and Phase 2. In Phase 1, response will be assessed by an investigator; in Phase 2 response will be 
assessed by an investigator and by an IERC. 
For all subjects, tumor response assessment will be performed by CT or MRI of the 
chest/abdomen/pelvis (plus other regions as required for specific tumor types) and other 
established assessments of tumor burden if CT/MRI imaging is insufficient for the individual 
subject. All scans performed at baseline and other imaging performed as clinically required 
(other supportive imaging) will be repeated at subsequent visits. In general, lesions detected at 
baseline should be followed using the same imaging methodology and preferably the same 
imaging equipment at subsequent tumor evaluation visits. 
For each subject, the investigator will designate 1 or more of the following measures of tumor 
status to follow for determining response: CT or MRI images of primary and/or metastatic tumor 
masses, physical examination findings, and results of other assessments. All available images 
collected during the trial period will be considered. The most appropriate measures to evaluate a 
subject’s tumor status should be used. Measure(s) chosen for sequential evaluation during the 
trial must correspond to measures used to document progressive tumor status that qualifies the 
subject for enrollment. 
In Phase 2, radiographic images used for local determination of disease progression will be read 
centrally and reviewed by a blinded IERC. The IERC will make a determination as to whether 
criteria for tumor response or progression according to RECIST 1.1 have been met. 
Tumor responses to treatment will be assigned based on evaluation of response of target, non- 
target, and new lesions according to RECIST 1.1 (all measurements should be recorded in metric 
notation; see Eisenhauer et al 2009). Assessment of tumor response by the IERC will be defined 
in the IERC Charter. 
• To assess objective response, tumor burden at baseline will be estimated and used for 
comparison with subsequent measurements. At baseline, tumor lesions will be 
categorized in target and non-target lesions as described by Eisenhauer et al (2009). 
Results for these evaluations will be recorded with as much specificity as possible so that pre- 
and post-treatment results will provide the best opportunity for evaluating tumor response. 
Any complete response (CR) or partial response (PR) should be confirmed as described by 
Eisenhauer et al (2009). 
In the case of a PR or CR, a confirmatory CT or MRI scan must be conducted ≥ 28 days 
later. 
The investigator may perform scans in addition to a scheduled trial scan for medical reasons or if 
progressive disease is suspected. 

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6.4.5. 
Pharmacokinetic, Pharmacodynamic, Genetic, and Other Assessments 
Sample collection, labeling, storage and shipment instructions will be provided in the 
operations/laboratory manual. 
A full chain of custody will be maintained for all samples throughout their lifecycle. Sponsor 
will keep oversight of the entire life cycle through internal procedures, monitoring of study sites, 
and auditing of external laboratory providers. 
6.4.5.1. 
Pharmacokinetic Assessments 
Blood samples will be collected in both study phases for plasma AGEN2034 concentration 
determinations (for pharmacokinetic evaluation). 
In Phase 1, PK samples will be collected as shown in Table 11 or Table 12.  
In Phase 2, PK samples will be collected as shown in Table 14. 
It is important to record all infusion start dates/times, infusion end dates/times, infusion 
interruption(s) start and end dates/times, infusion flush end dates/times, and blood sample 
collection dates/times completely and accurately (and to the nearest minute). 
6.4.5.2. 
Immunogenicity Assessment 
Blood samples for assessment of the immunogenicity of AGEN2034 will be collected for all 
subjects at the time points described in Section 6.1 (Phase 1). 
In Phase 2, ADA samples will be collected as shown in Table 14. 
The immunogenicity assessment will be conducted to detect and measure ADA (antibody against 
AGEN2034).  
6.4.5.3. 
Blood Biomarker Assessments 
To complete all assessments on blood samples (whole blood and plasma), the Sponsor or 
designated contract research organization (CRO) will provide instructions and necessary supplies 
to the site, including shipping materials and prepaid mailers. Refer to the Laboratory Manual for 
detailed information. 
All proposed biomarker analyses are exploratory objectives and are dependent on the quality and 
availability of sufficient materials. Collection and storage of samples will be detailed in the 
Laboratory Manual. The panel of biomarkers might be adjusted based on results from ongoing 
research related to anti–PD1/PD- L1 and anti-CTLA-4 therapies and/or safety. 
6.4.5.3.1. In Phase 1 
6.4.5.3.1.1. RECEPTOR OCCUPANCY 
In Phase 1 only, PD-1 receptor occupancy on circulating T cells will be measured as an 
indication of target engagement. 

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6.4.5.3.1.2. IMMUNOPHENOTYPING 
Leukocyte subpopulations and immune activation status will be assessed by flow cytometric 
analysis and/or transcriptional profiling by either RNAseq or other comparable technology using 
PBMCs. T cell lymphocytes, B lymphocytes, and natural killer cells (TBNK) profiling will be 
assessed by flow cytometric analysis using whole blood. All analyses will follow the schedule of 
events shown in Section 6.1. A complete differential blood count will be provided for each time 
point for calculations of absolute lymphocyte counts. As biomarker research is constantly 
evolving, selection of markers with the highest specificity and relevance to treatment effect may 
change. 
6.4.5.3.1.3. CYTOKINE ASSESSMENT 
In Phase 1 only, cytokine profiles will be evaluated at various time points from plasma samples 
collected according to Section 6.1. 
6.4.5.3.2. In Phase 2 
 The blood 
collection schedule for biomarker assessments in Phase 2 is detailed in in Table 14. 
6.4.5.3.2.1.  
 
 
 
6.4.5.3.2.2. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6.4.5.4. 
Pharmacogenomics Assessments (Optional) 
The Sponsor may conduct research on DNA from blood or tumor tissue specimens collected 
during this trial. This research may include genetic analysis (DNA) and gene expression profiling 
(RNA).  
Germline (inherited) variants will be investigated in DNA extracted from the whole blood. For 
this purpose, an additional 4 mL of whole blood (PGx sample) will be collected at screening. 
Additionally, tumor biopsy samples may be used for the extraction of DNA to study tumor 
genetics (somatic variations). Participation is optional for subjects being recruited at sites whose 
IEC/IRB has approved pharmacogenomics assessments and a pharmacogenomics ICF (optional) 
is signed.  
All samples collected during the trial will be kept confidential. For this purpose, the samples will 
be given a label connected with a code assigned at the start of the Main Study (coded trial subject 
number). Outside the study center, no one will be able to link the subject’s identity to the subject 
number. The link between the subject’s identity and the subject number will only be known by a 
limited number of authorized personnel. Information about race, ethnicity, sex, medical history, 
etc, may be available to scientists studying the PGx blood samples. Such information might be 
important for research or public health purposes. Genomic analysis results will not be reported 
back to the sites. 
Participation in pharmacogenomics portion of the trial is optional, requires separate informed 
consent, and will not affect participation in the main trial. Subjects may withdraw consent from 
pharmacogenomics portion of the trial without withdrawing from the trial. Consent and 
withdrawal of consent (if applicable) for pharmacogenomics assessments will be documented in 
the eCRF. 
6.4.6. 
Local Laboratory Tests 
It is essential that the Sponsor be provided with a list of laboratory normal ranges before 
shipment of study drug. Any change in laboratory normal ranges during the trial will additionally 
be forwarded to the CRO and the Sponsor. 
Blood samples will be collected from non-fasted subjects. All routine laboratory analyses will be 
performed at a laboratory facility local to the investigational site. 
The overall amount of blood to be drawn for safety laboratory testing, pregnancy testing, and 
exploratory biomarker investigation from a single subject with a body weight ≤ 70 kg (154 lb) 
must not exceed 120 mL/week. 
Laboratory tests for screening should be performed within 7 days prior to the first dose of trial 
treatment. After Cycle 1, predose laboratory procedures can be conducted up to 48 hours prior to 
dosing. 

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Results must be reviewed by the investigator or qualified designee and found to be acceptable 
prior to each dose of trial treatment. 
The report of the results must be retained as a part of the subject’s medical record or source 
documents. Blood samples for study related tests will be collected at time points specified in per 
Section 6.1 (Phase 1) or Section 6.2 (Phase 2). 
Laboratory tests are shown in Table 15. 
Table 15: Required Local Laboratory Panel Tests 
Full Chemistry 
Albumin 
Alkaline phosphatase1 
ALT (SGPT) 1 
Amylase 
AST (SGOT) 1 
BUN/total urea1 
Calcium1 
Chloride1 
Cholesterol  
Creatine kinase  
Creatinine1 
CRP 
GGT 
Glucose1 
LDH 
Lipase 
Magnesium1 
Phosphorus/phosphates1 
Potassium1 
Sodium1 
Total bilirubin1 
Total protein 
Triglycerides 
Uric acid 
Pregnancy Tests  
Serum pregnancy test  
Urine pregnancy test 
Hematology 
Absolute lymphocyte count  
Absolute neutrophil count 
Hematocrit 
Hemoglobin 
MCH 
MCHC 
MCV 
Platelet count 
RBC 
WBC and differential count 
Coagulation Studies 
aPTT 
Prothrombin time (INR) 
Endocrine Function Tests 
ACTH 
FSH (for postmenopausal women if applicable)  
T4 
TSH 
Autoimmunity Tests 
Anti-nuclear antibody (Phase 1 only) 
Rheumatoid factor (Phase 1 only) 
Abbreviations: ACTH: adrenocorticotropic hormone; ALT: alanine aminotransferase; aPTT: activated partial 
thromboplastin time; AST: aspartate aminotransferase; BUN: blood urea nitrogen; CRP: C-reactive protein; 
FSH: follicle-stimulating hormone; GGT: gamma glutamyl transferase; INR: international normalized 
ratio; LDH: lactate dehydrogenase; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular 
hemoglobin concentration; MCV: mean corpuscular volume; RBC: red blood cell; SGOT: serum glutamic 
oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; T4: free thyroxine; TSH: thyroid-
stimulating hormone; WBC: white blood cell. 
1Core serum chemistries. 
 

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7. 
ADVERSE EVENTS 
7.1. 
Adverse Event Definitions  
7.1.1. 
Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal 
product, whether or not considered related to the medicinal product. In cases of surgical or 
diagnostic procedures, the condition/illness leading to such a procedure is considered as the AE 
rather than the procedure itself. 
The investigator is required to Grade the severity/intensity of each AE. Investigators will 
reference NCI CTCAE v4.03, which is a descriptive terminology that can be used for AE 
reporting. A general grading (severity/intensity) scale is provided at the beginning of the 
referenced document, and specific event Grades are also provided. If a particular AE’s 
severity/intensity is not specifically Graded by the guidance document, the investigator is to 
revert to the general definitions of Grade 1 through Grade 5 and use his/her best medical 
judgement. 
The 5 general Grades of AE severity are:  
 
Grade 1: Mild 
 
Grade 2: Moderate 
 
Grade 3: Severe 
 
Grade 4: Life-threatening or disabling  
 
Grade 5: Death related to AE 
According to the Sponsor’s convention, if a severity/intensity of Grade 4 or 5 is applied to an 
AE, the investigator must also report the event as an SAE as per Section 7.2.2. However, a 
laboratory abnormality with a severity/intensity of Grade 4, such as anemia or neutropenia, is 
considered serious only if the condition meets one of the serious criteria described below. 
In the case of death, the primary cause of death or the event leading to death should be recorded 
and reported as an SAE. “Fatal” will be recorded as the outcome of this respective event; death 
will not be recorded as separate event. Only if no cause of death can be reported (e.g., sudden 
death, unexplained death), might the death per se be reported as an SAE. 
Investigators must also systematically assess the causal relationship of AEs to AGEN2034 using 
the following definitions. Decisive factors for assessment of causal relationship of an AE to 
AGEN2034 include, but may not be limited to, temporal relationship between the AE and 
AGEN2034, known side effects of AGEN2034, medical history, concomitant medication, course 
of the underlying disease, and trial procedures. 
Not related: Not suspected to be reasonably related to AGEN2034. AE could not medically 
(pharmacologically/clinically) be attributed to the AGEN2034 under study in this clinical 
trial protocol. A reasonable alternative explanation must be available. 

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Related: Suspected to be reasonably related to AGEN2034. AE could medically 
(pharmacologically/clinically) be attributed to the AGEN2034 under study in this clinical 
trial protocol. 
7.1.2. 
Abnormal Laboratory Findings and Other Abnormal Investigational Findings 
Abnormal laboratory findings and other abnormal investigational findings (e.g., on an ECG 
trace) should not be reported as AEs unless they are associated with clinical signs and symptoms, 
lead to treatment discontinuation, or are considered otherwise medically important by the 
investigator. If an abnormality fulfills these criteria, the identified medical condition (e.g., 
anemia, increased ALT) must be reported as the AE rather than the abnormal value itself. 
7.1.3. 
Adverse Drug Reaction  
An ADR is defined in this trial as any AEs suspected to be related to AGEN2034 by the 
investigator and/or Sponsor. 
7.1.4. 
Serious Adverse Event  
An SAE is any untoward medical occurrence that at any dose: 
• Results in death. 
• Is life-threatening. 
Note: The term “life-threatening” in this definition refers to an event in which the subject 
is at risk of death at the time of the event; it does not refer to an event that hypothetically 
might cause death if it were more severe. 
• Requires in-patient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• An overdose of Sponsor's product, as defined in Section 7.5 
• Is otherwise considered as medically important 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered as SAEs when, based on appropriate medical judgement, they 
may jeopardize the subject or may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in in subject hospitalization, or development of drug dependency or drug abuse. 
For purposes of reporting, any suspected transmission of an infectious agent via a study drug is 
also considered a serious adverse reaction, and all such cases should be reported in an expedited 
manner as described in Section 7.2.2. 
7.1.5. 
Events That Do Not Meet the Definition of an SAE 
Elective hospitalizations to administer or to simplify trial treatment or trial procedures (e.g., 
overnight stay to facilitate chemotherapy and related hydration therapy application) are not 

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considered SAEs. However, all events leading to unplanned hospitalizations or unplanned 
prolongation of an elective hospitalization (e.g., undesirable effects of any administered 
treatment) must be documented and reported as SAEs. 
7.1.6. 
Events not to be Considered as AEs/SAEs 
Medical conditions present at the initial trial visit that do not worsen in severity or frequency 
during the trial are defined as baseline medical conditions, and are not to be considered AEs. 
7.1.7. 
AE/SAEs Observed in Association with Disease Progression 
Disease progression recorded in the course of efficacy assessments only, but without any adverse 
signs or symptoms, should not be reported as an AE. However, if adverse signs or symptoms 
occur in association with disease progression, these should be recorded as AEs and as SAEs if 
they meet any seriousness criteria. 
7.1.8. 
Predefined Potential AEs of Special Interest for Safety Monitoring 
Selected non-serious and SAEs defined below are considered AESIs and must be recorded as 
such on the Adverse Event case report forms/worksheets and reported within 24 hours to the 
Sponsor either by electronic media or paper. Sponsor Contact information can be found in the 
Investigator Trial File Binder (or equivalent). 
Events of clinical interest for this trial include: 
• Infusion-related reactions. 
• An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit 
of normal and an elevated total bilirubin lab value that is greater than or equal to 2X 
the upper limit of normal and, at the same time, an alkaline phosphatase lab value that 
is less than 2X the upper limit of normal, as determined by way of protocol-specified 
laboratory testing or unscheduled laboratory testing. 
Note: These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may 
require an additional evaluation for an underlying etiology. The trial site guidance for 
assessment and follow up of these criteria can be found in Section 5.6.4. 
• Any AE that is reasonably suspected to be immune-mediated (ie, an irAE). 
AESIs (both non-serious and serious AEs) identified in this guidance document from the date of 
first dose through 90 days following cessation of treatment, or 30 days after the initiation of a 
new anticancer therapy, whichever is earlier, need to be reported to the SPONSOR within 
24 hours of the event, regardless of attribution to study treatment, consistent with standard SAE 
reporting guidelines and either by electronic media or paper. 
Subjects should be assessed for possible AESIs prior to each dose. Lab results should be 
evaluated and subjects should be asked for signs and symptoms suggestive of an immune-related 
event. Subjects who develop an AE thought to be immune-related should have additional testing 
to rule out other etiologic causes. If lab results or symptoms indicate a possible irAE, then 
additional testing should be performed to rule out other etiologic causes. If no other cause is 
found, then it is assumed to be immune-related. 

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Any infusion reaction, regardless of Grade, must be reported in an expeditious manner and will 
be considered an AESI. The reporting of AESI is described in Section 7.2.2. 
7.2. 
Methods of Recording and Assessing Adverse Events 
At each trial visit, the subject will be queried on changes in his/her condition. During the 
reporting period of the trial, any unfavorable changes in the subject’s condition will be recorded 
as AEs, whether reported by the subject or observed by the investigator. 
Complete, accurate, and consistent data on all AEs experienced for the duration of the reporting 
period (defined below) will be reported on an ongoing basis in the appropriate section of the 
eCRF. Among these AEs, all SAEs and all non-serious AESIs must be additionally documented 
and reported using the appropriate report form as described in Section 7.2.2. 
It is important that each AE report include a description of the event, its duration (onset and 
resolution dates and times to be completed when it is important to assess time of AE onset 
relative to recorded treatment administration time), its severity, causal relationship with trial 
treatment, any other potential causal factors, any treatment administered or other action taken 
(including dose modification or discontinuation of study drug), and outcome. In addition, serious 
cases should be identified and the appropriate seriousness criteria documented. 
Specific guidance can be found in the eCRF Completion and Monitoring Conventions. 
7.2.1. 
Definition of the Adverse Event Reporting Period 
The AE reporting period for safety surveillance begins when the subject provides written consent 
and continues until either 90 days after the last dose of study drug or the start of new anticancer 
treatment, whichever comes first. Following the End-of-Treatment Safety Follow-up Visit, only 
treatment-related AEs will be documented through the Treatment Follow-up Period of up to 
12 months after the last dose of study drug or until disease progression and/or initiation of a new 
line of therapy, whichever comes first. 
Any SAE suspected to be related to trial treatment must be reported whenever it occurs, 
irrespective of time elapsed since last dose of study drug. 
7.2.2. 
Procedure for Reporting SAEs / AESIs 
All adverse reactions will be reported to the FDA according to 21 Code of Federal Regulations 
(CFR) 312.32 and according to applicable regulatory authorities and institutional ethics 
committees. 
7.2.2.1. 
Serious Adverse Events 
In the event of any new SAE (of any Grade) occurring during the reporting period, the 
investigator must immediately (i.e., ≤ 24 hours after becoming aware of the event) inform the 
Sponsor or designee by telephone, fax, or e-mail. For the following significant SAEs the 
reporting period to the Sponsor is ≤ 8 hours after becoming aware of the event: 
• Drug-related death less than 30 days of dosing 
• Drug-related life-threatening event. 

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When an event (or follow-up information) is reported by telephone, a written report must be sent 
immediately thereafter by fax or e-mail. 
Reporting procedures and timelines are the same for any new information on a previously 
reported SAE (= follow-up). 
For names, addresses, telephone, and fax numbers for SAE reporting, see information included 
on the SAE report form. 
All written reports should be transmitted using the SAE report form, which must be completed 
by the investigator following specific completion instructions. The AE section of the eCRF must 
be completed. Relevant pages from the eCRF may be provided in parallel (e.g., medical history, 
concomitant drugs). 
In all cases, information provided in the SAE report form must be consistent with data on the 
event that is recorded in the corresponding eCRF sections. 
The investigator/reporter must respond to any request for follow-up information (e.g., additional 
information, outcome and final evaluation, specific records where needed) or to any question the 
Sponsor or designee may have regarding the AE within the same timelines as described for 
initial reports. This is necessary to permit a prompt assessment of the event by the Sponsor or 
designee and (as applicable) to allow the company to meet strict regulatory timelines associated 
with expedited safety reporting obligations. 
Requests for follow-up will usually be made by the responsible monitor, although in exceptional 
circumstances the Sponsor’s global drug safety department may contact the investigator directly 
to obtain clarification or to discuss a particularly critical event. 
7.2.2.2. 
Adverse Events of Special Interest 
In the event of a non-serious AESI, the investigator must complete the AESI report form and 
send it to the Sponsor/designee immediately, within 24 hours. Names, addresses, and telephone 
and fax numbers for AESI reporting will be included on the report form. Serious AESIs must be 
reported in an expedited manner as SAEs, as outlined above. 
7.2.2.3. 
Safety Reporting to Health Authorities, Independent Ethics
 
Committees/ Institutional Review Boards, and Investigators 
The Sponsor will send appropriate safety notifications to health authorities in accordance with 
applicable laws and regulations. 
The investigator must comply with any applicable site-specific requirements related to reporting 
of SAEs (and in particular deaths) involving his/her subjects to the IEC/IRB that approved the 
trial. 
In accordance with International Conference on Harmonization Good Clinical Practice (GCP) 
guidelines, the Sponsor or designee will inform the investigator of “findings that could adversely 
affect the safety of subjects, impact the conduct of the trial, or alter the IEC’s/IRB’s 
approval/favorable opinion to continue the trial.” In accordance with respective regulations, the 
Sponsor or designee will inform the investigator of AEs that are both serious and unexpected, 
and are considered to be related to the administered product (suspected unexpected serious 
adverse reactions [SUSARs]). The investigator should place copies of safety reports in the 

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investigator site file. National regulations with regard to safety report notifications to 
investigators will be taken into account. 
When specifically required by regulations and guidelines, the Sponsor or designee will provide 
appropriate safety reports directly to the concerned health authority and lead IEC/IRB, and will 
maintain records of these notifications. When direct reporting by the Sponsor or designee is not 
clearly defined by national or site-specific regulations, the investigator will be responsible for 
promptly notifying the concerned IEC/IRB of any safety reports provided by the Sponsor or 
designee, and for filing copies of all related correspondence in the investigator site file. 
7.3. 
Monitoring of Subjects with Adverse Events 
Adverse events are recorded and assessed continuously throughout the trial starting at the time 
the subject receives his/her first treatment (Section 7.2.1) and are assessed for final outcome at 
the end-of-treatment visit. 
After the End-of-Treatment Safety Follow-up Visit, only treatment-related AEs will be 
documented through the Treatment Follow-up Period of up to 12 months after the last dose of 
study drug or until disease progression and/or initiation of a new line of therapy. 
All SAEs ongoing at the post-treatment safety follow-up visit must be monitored and followed 
by the investigator until stabilization or until the outcome is known, unless the subject is 
documented as “lost to follow-up.” 
Reasonable attempts to obtain this information must be made and documented. It is also the 
responsibility of the investigator to ensure that any necessary additional therapeutic measures 
and follow-up procedures are performed. 
7.4. 
Pregnancy and In Utero Drug Exposure 
Only pregnancies considered by the investigator as related to trial treatment (e.g., resulting from 
a drug interaction with a contraceptive medication) are considered as AEs. 
However, all pregnancies with an estimated conception date during the period defined in 
Section 7.2.1 must be recorded by convention in the AE page/section of the eCRF. 
The same rule applies to pregnancies in female subjects and in female partners of male subjects. 
The investigator must notify the Sponsor or designee in an expedited manner of any pregnancy 
using the pregnancy report form, which must be transmitted according to the same process as 
described for SAE reporting in Section 7.2.2. 
Investigators must actively follow up, document, and report the outcome of these pregnancies, 
even if subjects are withdrawn from the trial. A separate consent will be obtained for follow-up 
of these subjects. 
The investigator must notify the Sponsor or designee of these outcomes using the pregnancy 
report form and, in case of abnormal outcome, the SAE report form if the subject sustains an 
event and the parent-child/fetus AE report form when the child/fetus sustains an event). 
Any abnormal outcome must be reported in an expedited manner, as described in Section 7.2.2, 
whereas normal outcomes must be reported within 45 days from delivery. 

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In the event of a pregnancy in a subject occurring during the course of the trial, the subject must 
be discontinued from trial medication immediately. The Sponsor or designee must be notified 
without delay and the subject must be followed as described above. 
7.5. 
AGEN2034 Overdose 
An overdose is defined as any dose 5% greater than the highest daily dose included in the 
clinical trial protocol. Any overdose must be recorded in the trial medication section of the 
eCRF. 
For monitoring purposes, any case of overdose, whether or not associated with an AE (serious or 
non-serious), must be reported to the Sponsor’s or designated CRO’s global drug safety 
department in an expedited manner using the SAE report form. 
There is no data on AGEN2034 overdose to date. Data available with agents from the same class 
indicate that the correlation between dose and toxicity is relatively flat. 
The investigator should use his or her clinical judgement when treating an overdose of 
AGEN2034. 
8. 
STATISTICAL CONSIDERATIONS 
This section outlines the core elements of the planned statistical summaries and analyses for the 
data collected in this study.  
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a Statistical Analysis Plan (SAP), which will be maintained by the Sponsor. 
The SAP may modify the plans outlined in the protocol; however, any major modifications of the 
primary endpoint definition and/or its analysis will also be reflected in a protocol amendment. If, 
after the data are locked, changes are made to the SAP, then these deviations will be documented 
in the Clinical Study Report (CSR). 
8.1. 
Sample Size 
The study includes 2 phases: Phase 1: Dose Escalation Phase, and Phase 2: Expansion Phase. 
The total sample size for both phases is expected to be approximately 200 subjects. 
8.1.1. 
Phase 1 
It is expected that approximately 50 subjects will be enrolled in the Phase 1 part of the study. 
The sample size in the Phase 1 is not driven by statistical hypothesis testing, but driven by 
clinical considerations. Final sample size in this phase may vary depending on the total number 
of dose levels to be tested, and subject replacement for DLT evaluation, if applicable. 
8.1.2. 
Phase 2 
The aim in this phase is to detect preliminary evidence of clinical activity in subjects with 
metastatic cervical cancer. The primary endpoint is the ORR per IERC based on RECIST 1.1. 
ORR will be estimated as binomial proportion of best overall response (BOR) of confirmed PR 

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or CR and reported with 95% Wilson score confidence interval (CI); the CI will be interpreted as 
a plausible range for a true (unobserved) ORR. 
Phase 2 is expected to enroll approximately 150 subjects. With 150 subjects in the final analysis, 
the power to exclude an ORR of 5% by the lower limit of the 95% Wilson score interval is 
92.2% and 96.2%, assuming a true ORR of 12% and 13%, respectively. The sample size will 
provide ≥ 77% probability to observe an AE with and underlying rate of ≥ 1%. With 100 patients 
in the interim analysis, the power to exclude an ORR of 5% by the lower limit of the two-sided 
95% Wilson score interval will be 77.4% and 85.2%, assuming a true ORR of 12% and 13%, 
respectively. 
Historical published data may be used for the interpretation of the clinical significance of the 
study endpoints. 
Interim analyses will be performed to assess the safety and efficacy (using the ORR and selected 
secondary efficacy endpoints) when (1) data are available for approximately 30 subjects treated 
for at least 3 months and (2) approximately 3 months after approximately 100 patients are dosed. 
No early stopping for efficacy will be performed, as a more complete safety assessment and 
evaluation of durability of responses is necessary for determination of risks and benefits. 
Consequently, interim analyses will not affect the overall type I error. A non-binding futility 
analysis may be performed using methods described in the statistical analysis plan. Additional 
interim analyses for safety and efficacy assessment may performed.  
8.2. 
Analysis Sets 
The following analysis sets will be defined and used separately for Phase 1 and Phase 2, as 
applicable: 
• Phase 1 DLT analysis set: All subjects with data used for implementing the 
confirmation of the safety of the combination. These subjects should have received all 
study treatment administrations in the DLT evaluation period or should have stopped 
treatment because of DLTs in the DLT evaluation period. 
• Safety analysis set: All subjects who have received ≥ 1 dose of trial treatment. 
• Pharmacokinetics analysis set: All subjects who have completed ≥ 1 infusion of study 
drug, and who have provided sufficient concentration measurements. 
• Evaluable efficacy analysis set: All subjects in Phase 2 who have received ≥ 1 dose of 
trial treatment and have measurable disease at baseline, according to the IERC 
assessment. 
8.3. 
Description of Statistical Analyses 
8.3.1. 
General Considerations 
All data recorded during the study will be presented in individual data listings performed on the 
safety analysis set. All data will be evaluated as observed, and no imputation method for missing 
values will be used unless otherwise specified. All data will be presented in a descriptive 
manner. Statistical inference of the primary efficacy endpoint will be performed for the efficacy 
expansion cohort based on the pre-planned significance level. 

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Descriptive statistics will be used in general to summarize trial results, i.e., statistics for 
continuous variables may include means, standard deviations, medians, and ranges (min, max). 
Categorical variables will be summarized by counts and percentages. Unless otherwise specified, 
calculation of proportions will be based on the number of subjects in the analysis set of interest. 
Counts of missing observations will be included in the denominator and presented as a separate 
category if not otherwise specified in the SAP. 
The DLT analysis set is the underlying dataset for determination of the safety. Safety analyses 
will be performed on the Safety analysis set. Analyses of PK variables will be performed on the 
PK analysis set. The primary analysis of the ORR and other efficacy variables will be based on 
the evaluable efficacy analysis set, defined as all subjects dosed with study drug who had 
measurable disease at baseline by IERC assessment. Details of the analysis will be described in 
the SAP. 
Unless otherwise specified, endpoint analyses will be performed separately for Phase 1 and 
Phase 2. 
8.3.2. 
Analysis of Primary Endpoints 
8.3.2.1. 
In Phase 1: Dose-limiting Toxicity  
For determination of safety of AGEN2034, individual subject data from the Phase 1 portion of 
the trial will be reported. In addition, for final statistical analysis, the following will be 
summarized: 
• At each dose level, number and proportion of subjects in the DLT analysis set who 
experience a DLT during the DLT evaluation period. 
• At each dose level, number and proportion of TEAEs experienced by subjects in the 
DLT analysis set during the DLT evaluation period. 
8.3.2.2. 
In Phase 2: Objective Response Rate 
• The primary endpoint for Phase 2 is the confirmed ORR according to RECIST 1.1, as 
determined by an IERC. ORR will be estimated as the binomial proportion of patients 
with BOR of PR or CR, taking into account the following requirement for confirmation: 
for PR or CR, confirmation of the response according to RECIST 1.1 will be required at 
no sooner than 4 weeks after initial documentation of CR or PR. ORR will be reported 
with two-sided, 95% Wilson score CI. 
8.3.3. 
Analysis of Secondary Endpoints 
The following secondary endpoints will be summarized. 
8.3.3.1. 
Efficacy Parameters  
Efficacy parameters, including confirmed ORR according to RECIST 1.1, as determined by 
investigator; disease control rate (DCR), defined as proportion of subjects with CR, PR, or SD 
for at least 12 weeks; duration of response (DOR) according to RECIST 1.1; time to response 
(TTR); and duration of stable disease, defined as time from treatment start until documented 

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progression, will be listed and summarized in Phase 2 using both IERC and investigator 
assessments. 
DOR and TTR will be summarized in only a subset of patients with confirmed response using 
the Kaplan-Meier method and displayed graphically, where appropriate. The median event time 
and 95% CI for the median will be provided. Duration of stable disease will also be summarized 
by the Kaplan-Meier method.  
In addition, PFS, and OS time will be presented in subject listings, analyzed using Kaplan-Meier 
method and displayed graphically where appropriate. The median event time and 95% CI for the 
median will be provided. 
8.3.3.2. 
Pharmacokinetic Parameters 
Both noncompartmental (NCA) and compartmental modeling (e.g., population PK [PopPK]) 
techniques will be used to analyze AGEN2034 PK. 
The PK parameters to be estimated and reported may include, but may not be limited to: 
maximum drug concentration observed postdose at steady-state (Cmax-ss); minimum observed 
concentration at steady-state (Cmin-ss); area under the drug concentration-time curve (AUC) 
within a dosing interval within the time span t1 to t2 at steady-state (AUC(t1-t2)-ss); AUC from 
time of dosing (0 h) to time t, the time of last observation (calculated by linear trapezoidal 
summation) (AUC0-t); AUC from time of dosing (0 h) extrapolated to infinity (calculated by 
linear trapezoidal summation and extrapolated to infinity using Clast/λz) (AUC0-∞); time to 
maximum observed concentration (ie, time at which Cmax occurs) (tmax); terminal disposition rate 
constant, determined from the slope of the regression line of log (concentration) vs. time (λz); 
terminal elimination half-life, determined as 0.693/ λz (t½ or HL); systemic clearance (CL); and 
volume of distribution (Vd). 
8.3.3.3. 
Immunogenicity 
Antidrug antibody concentrations in correlation with AGEN2034 PK exposure matrix will be 
summarized. 
8.3.3.4. 
Exploratory Biomarkers  
Summary statistics for biomarkers will be provided for all preplanned time points. Changes from 
baseline for continuous biomarkers may also be presented as applicable and categorical 
biomarkers will be tabulated. 
Possible relationship of biomarker levels with efficacy may be investigated. 
8.3.4. 
Safety Analyses 
The extent of exposure to AGEN2034 will be characterized by duration (weeks), number of 
administrations, cumulative dose (mg/kg), dose intensity (mg/kg/week), relative dose intensity 
(actual dose given/planned dose), number of dose reductions, and number of dose delays. 
Safety analyses will be performed on the safety analysis set. Safety endpoints will be 
summarized by dose cohort in each phase. 

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Safety assessments will be based on incidence of AEs, including AESIs, ADRs, immunogenicity, 
and changes in vital signs (including body weight), ECG, and laboratory values (hematology and 
serum chemistry). 
The on-treatment period is defined as time from first dose of study treatment to last dose of study 
drug plus 30 days, or the earliest date of new anticancer therapy minus 1 day, whichever occurs 
first. 
8.3.4.1. 
Adverse Events 
Adverse events will be coded according to Medical Dictionary for Regulatory Activities 
(MedDRA) version 21.0. Severity of AEs will be graded using CTCAE (version 4.03) toxicity 
grading scale whenever possible. 
Treatment-emergent AEs are AEs with onset dates during the on-treatment period, or the 
worsening of an event during the on-treatment period. Incidence of TEAEs, regardless of 
attribution, and AEs defined as related to AGEN2034 will be summarized by system organ class 
and preferred term, and described in terms of severity and relationship to AGEN2034.  
Analysis of AES will be performed for events that are considered as treatment emergent. 
Adverse events leading to death or discontinuation of trial treatment, events with CTCAE 
Grade 3 or higher, study drug-related events, and SAEs will be summarized. 
Indications of dose-related ADRs will also be examined.  
8.3.4.2. 
Laboratory Variables 
Laboratory results will be classified by grade according to NCI CTCAE. The worst on-trial 
grades after first trial treatment will be summarized. Shifts in toxicity grading from first 
treatment to highest grade will be tabulated. Results for variables that are not part of NCI 
CTCAE will be presented as below, within, or above normal limits. Only subjects with post-
baseline laboratory values will be included in these analyses. 
8.3.4.3. 
Physical Examination, Vital Signs, and Electrocardiogram 
Physical examination data, vital signs (body temperature, respiratory rate, heart rate, and blood 
pressure), and 12-lead ECG data will be presented. 
8.3.5. 
Interim and Final Analysis 
Phase 2 is designed to have at least 2 interim analyses of the primary endpoint and selected 
secondary efficacy and safety endpoints. No early stopping for efficacy will be performed, as a 
more complete assessment of safety and durability of responses will be required for evaluation of 
risks and benefits. Consequently, the overall type I error will not be affected by the interim 
analyses. A non-binding futility analysis may be performed using methods described in the SAP. 
The first interim analysis will be performed when data are available for approximately 30 subjects 
treated for at least 3 months. The primary analysis of efficacy and safety data will include all 
subjects dosed prior to a borderline date (specified as at least 3 months prior to the data cutoff). 
Another interim analysis will be performed 3 months after approximately 100 subjects have been 
dosed and will include, as the primary analysis of safety and efficacy, all subjects in the evaluable 
efficacy analysis set among the first approximately 100 subjects dosed. Sensitivity safety analyses 

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will be performed on all subjects in the safety analysis set dosed as of the data cutoff. Details of 
the interim analyses will be provided in a separate SAP. 
Additional interim analyses for safety and efficacy assessment may be performed.  
The final analysis will be performed after study completion. 
The primary analysis set for efficacy assessment will be the evaluable efficacy analysis set. The 
primary analysis set for safety assessment will be the safety analysis set.  
The interim analyses may include PD-1 expression data if available. Details will be provided in a 
separate SAP. After the interim analyses, subsequent enrollment of subjects may be based on 
biomarker enrichment (including but not limited to PD-L1 expression). In such cases, tumor 
tissue must be positive for the selected entry biomarker prior to subject enrollment. 
9. 
TRIAL GOVERNANCE AND OVERSIGHT 
9.1. 
Safety Monitoring Committee 
A Safety Monitoring Committee (SMC) will regularly review safety data to ensure subjects’ 
safety throughout the study. 
The SMC will consist of permanent members from the Sponsor and/or CRO: 
• Sponsor: head of development/chief medical officer, pharmacovigilance physician, 
study physician, and Principal Investigator(s). 
• CRO: lead statistician and study physician. 
During the Phase 1 portion of the trial, the SMC assess safety; decide on dose-escalation and 
opening of backfill enrollment; define the recommended Phase 2 dose (RP2D); and determine 
opening of the Phase 2 cohorts. The SMC recognizes that with the limited prior human 
experience with AGEN2034, a conservative approach will be adopted in ascribing the 
relationship of the treatment-related toxicity to the drug. 
At each SMC review, all safety information of the participating subjects will be reviewed and the 
SMC will decide by consensus on continuation, modification, or suspension of the trial. 
The SMC may modify the frequency of meetings as deemed appropriate during the course of the 
trial. The specific working procedures will be described in a separate SMC charter. 
9.2. 
Independent Endpoint Review Committee 
For the Phase 2 portion of the study, a central facility will read and interpret all radiographic 
scans for subjects enrolled in the study. Data for all images will be transferred from trial sites to 
the central reading center for evaluation. Scans will be evaluated at the central facility in 
accordance with RECIST 1.1. Imaging data will be transferred to the designee at regular 
intervals. A manual from the vendor will be provided to each trial site. 
For all subjects in Phase 2, the IERC will perform a blinded determination as to whether 
RECIST 1.1 criteria for tumor response or progression have been met. The IERC will be 
composed of a minimum of 3 properly qualified members. 

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The role of the IERC will be to review radiographic image findings for determination of the time 
point for overall response and date of disease progression (per RECIST 1.1) for each subject. 
The full membership, mandate, and processes of the IERC will be detailed in a separate IERC 
charter. 
9.3. 
Independent Data Monitoring Committee (IDMC) 
For the Phase 2 portion of the study, an IDMC will be established supplement the routine trial 
monitoring outlined in this protocol. The voting members of the committee are external to and 
independent of the Sponsor. The members of the IDMC must not be involved with the trial in 
any other way (e.g., they cannot be trial investigators) and must have no competing interests that 
could affect their roles with respect to the trial. The IDMC will include 4 oncologists (a 
minimum of 1 of which is experienced in cervical cancer) and 1 external statistician. 
The IDMC will make recommendations to the Sponsor regarding steps to ensure both subject 
safety and the continued ethical integrity of the trial. Also, the IDMC will review interim trial 
results, consider the overall risk and benefit to trial participants (see Section 8.3.5) and 
recommend to the Sponsor if the trial should continue in accordance with the protocol. 
Specific details regarding responsibilities and governance, including the roles and 
responsibilities of the various members and the Sponsor protocol team; meeting facilitation; the 
trial governance structure; and requirements for and proper documentation of IDMC reports, 
minutes, and recommendations will be described in a separate charter that is reviewed and 
approved by the IDMC. The IDMC will monitor the trial at an appropriate frequency, as 
described in the detailed IDMC charter. The IDMC will also make recommendations to the 
Sponsor protocol team regarding steps to ensure both subject safety and the continued ethical 
integrity of the trial. 
10. 
ETHICAL AND REGULATORY ASPECTS 
10.1. 
Ethics Review 
The study protocol, subject information and consent form, Investigator’s Brochures and bridging 
Investigator’s Brochure, any written instructions to be given to the subject, available safety 
information, subject recruitment procedures (e.g., study website), information about payments 
and compensation available to the subjects and documentation evidencing the investigator’s 
qualifications will be approved by the IRB/EC per local regulations prior to study start. The 
written approval should identify all documents reviewed by name and version. 
Changes in the conduct of the study or planned analysis will be documented in a protocol 
amendment. The investigator must submit and, where necessary, obtain IRB and/or Sponsor 
approval for all subsequent protocol amendments and changes to the ICF or changes of the 
investigational site, facilities, or personnel. The investigator should notify the IRB of protocol 
deviations or SAEs occurring at the site and other AE reports received from the Sponsor in 
accordance with local procedures. 
Safety updates for AGEN2034 will be prepared by the Sponsor or its representative as required, 
for submission to the relevant IRB. 

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10.2. 
Responsibilities of the Investigator 
The investigator is responsible for conduct of the trial at his/her site. He/she will ensure that the 
trial is performed in accordance with the clinical trial protocol and the approved protocol 
amendments; the current version of the Declaration of Helsinki (Ethical Principles for Medical 
Research Involving Human Subjects), ICH Good Clinical Practice (ICH E6 guideline) as 
adopted by the respective health authorities; and applicable Health Authority requirements and 
national and state laws. In particular, the investigator must ensure that only subjects who have 
given their written informed consent are included into the trial. 
10.3. 
Subject Information and Informed Consent 
An unconditional prerequisite for a subject’s participation in the trial is his/her written informed 
consent. The subject’s written informed consent to participate in the trial must be given before 
any trial-related activities are carried out. Subjects may also sign a separate, optional section of 
the ICF, related to pharmacogenomics, which refers to extraction and analysis of DNA from 
blood and/or tumor biopsy to better understand how gene(s) may affect the efficacy of 
AGEN2034. 
Adequate information must therefore be given to the subject by the investigator before informed 
consent is obtained. In addition to providing this written information to a potential subject, the 
investigator will inform the subject verbally of all pertinent aspects of the trial. The language 
used in doing so must be chosen so that the information can be fully and readily understood by 
lay persons. 
Informed consent will be obtained for participation in the trial and for optional participation in 
pharmacogenomics assessments. Additionally, should a female subject become pregnant in 
during the study, a separate informed consent for follow-up of the pregnancy will be obtained. 
The ICF must be signed and personally dated by the subject and investigator. The signed and 
dated declaration of informed consent will remain at the investigator’s site, and must be safely 
archived by the investigator so that the forms can be retrieved at any time for monitoring, 
auditing, and inspection purposes. A copy of the signed and dated information and ICF should be 
provided to the subject before participation. 
Whenever important new information becomes available that may be relevant to the subject’s 
consent, the written subject information sheet and any other written information provided to 
subjects will be revised by the Sponsor or designee and be submitted again to the IEC/IRB for 
review and favorable opinion. The agreed upon, revised information will be provided to each 
subject in the trial for signing and dating. The investigator will explain the changes to the 
previous version. 
10.4. 
Subject Identification and Privacy 
In compliance with ICH GCP guidelines, it is a requirement that the investigator and institution 
permit authorized representatives of the Sponsor, regulatory authorities, and IRB direct access to 
review the subject’s original medical records at the site for verification of trial-related procedures 
and data. 

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Measures to protect confidentiality include: only the study number, subject number, subject 
initials, and date of birth will identify the subject on the electronic case report form (eCRF) or 
other documents submitted to the Sponsor. This information will be used in the database for 
subject identification. Subject names or addresses will not be entered on the eCRF or in the 
database. No material bearing a subject’s name will be kept on file by the Sponsor. Subjects will 
be informed of their rights within the ICF. 
In studies conducted in the United States, confidentiality of subject’s personal data will be 
protected in accordance with the Health Insurance Portability and Accountability Act (HIPAA) 
of 1996 and national data protection laws, as applicable. HIPAA regulations require that in order 
to participate in the trial, a subject must sign an authorization from the trial that he or she has 
been informed of following: 
• What Protected Health Information (PHI) will be collected from subjects in this trial; 
• Who will have access to that information and why; 
• Who will use or disclose that information; 
• That health information may be further disclosed by the recipients of the information, 
and that if the information is disclosed the information may no longer be protected by 
federal or state privacy laws; 
• The information collected about the research trial will be kept separate from the 
subject’s medical records, but the subject will be able to obtain the research records 
after the conclusion of the trial; 
• Whether the authorization contains an expiration date; and 
• The rights of a research subject to revoke his or her authorization. 
In the event that a subject revokes authorization to collect or use his or her PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e., that the subject is alive) at the 
end of their scheduled trial period. 
10.5. 
Emergency Medical Support and Subject Card 
Subjects enrolled in this clinical trial will be provided with emergency medical support cards 
during their trial participation, which will be furnished by the Sponsor or designee. The 
emergency medical support card is based on the need to provide clinical trial subjects with a way 
of identifying themselves as participating in a clinical trial, and subsequently give health care 
providers access to information about this participation that may be needed to determine the 
course of the subject’s medical treatment. 
This service is designed to provide information to health care providers who are not part of the 
clinical trial. Clinical trial investigators, who are already aware of the clinical trial protocol and 
treatment, have other means of accessing the necessary medical information for management of 
emergencies occurring in their subjects. 

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The first point of contact for all emergencies will be the clinical trial investigator caring for the 
affected subject. The investigator agrees to provide his or her emergency contact information on 
the card for this purpose. If the investigator is available when an event occurs, he/she will answer 
any questions. Any subsequent action will follow the standard processes established for the 
investigators. 
In cases in which the investigator is not available, the site will provide the appropriate means to 
contact a physician. This includes provision of a 24-hour contact number at the facility, whereby 
the health care providers will be given access to an appropriate physician to assist with the 
medical emergency. 
10.6. 
Clinical Trial Insurance and Compensation to Subjects 
Insurance coverage shall be provided for each country participating to the trial. Insurance 
conditions shall meet good local standards, as applicable. 
10.7. 
Health Authorities 
The clinical trial protocol and any applicable documentation (e.g., investigational medicinal 
product dossier, subject information, and ICF) will be submitted or notified to health authorities 
by the Sponsor or designated CRO in accordance with regulations of the countries involved in 
the trial. 
11. 
TRIAL MANAGEMENT 
11.1. 
Sponsor and Trial Administrative Structure 
The Sponsor of this study is Agenus Inc. 
In countries where a local sponsor is required a qualified local legal Sponsor will be designated 
by Agenus, and will act as the legal Sponsor for the study, and will fulfil the obligations that this 
role entails. In these cases, the local legal Sponsor shall, to the extent required by the applicable 
laws and regulations, interact with regulatory and health authorities on behalf of the Sponsor in 
connection with this study. 
Details of logistical and administrative structures and associated procedures will be defined in a 
separate manual of operations, which will be prepared by the Sponsor or designated CRO. 
11.2. 
Investigational Sites 
The trial will be global, with approximately 10 to 15 enrolling centers participating in Phase 1 
and approximately 60 centers in Phase 2. 
11.3. 
Trial Coordination/Monitoring 
The Sponsor will coordinate the trial and may delegate certain trial activities to CROs, including 
certain laboratory assessments, safety reporting, biostatistics, etc. The Sponsor’s clinical 
operations department will oversee activities performed by CROs. 

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11.4. 
Data Collection 
The eCRF is the primary data collection instrument for the trial. The clinical site will keep 
eCRFs current to enable the monitor to review the subjects’ status throughout the course of the 
trial. To maintain confidentiality, only the study number, subject number, subject initials, and 
date of birth will identify the subject on the eCRF. All data requested on the eCRF must be 
supported by and be consistent with the subject’s source documentation. 
Source documents are the original documents, data, records and certified copies of original 
records of clinical findings, observations and activities from which the subject’s eCRF data are 
obtained. These can include, but are not limited to, hospital records, clinical and office charts, 
laboratory, medico-technical department and pharmacy records, diaries, microfiches, ECG 
traces, copies or transcriptions certified after verification as being accurate and complete, 
photographic negatives, microfilm or magnetic media, X-rays, and correspondence. 
All missing data must be explained. When a required laboratory test, assessment, or evaluation 
has not been done or an “Unknown” box is not an option on the eCRF, a note should be created 
verifying that the field was “Not Done” or “Unknown”. For any entry errors made, the error(s) 
must be corrected, and a note explaining the reason for change should be provided. 
The investigator will sign and date the subject eCRF casebook indicating that the data on the 
eCRF have been assessed. Each completed eCRF will be electronically signed and dated by the 
PI, once all data for that subject is final. 
11.5. 
Investigator Site File and Archiving 
The investigator will be provided with an investigator site file upon initiation of the trial. This 
file will contain all documents necessary for the conduct of the trial and will be updated by the 
site throughout the trial. It must be available for review by the monitor; be ready for Sponsor 
audit as well as for inspection by health authorities during and after the trial; and safely archived 
for ≥ 15 years (or per local requirements or as otherwise notified by the Sponsor) after the end of 
the trial. Documents to be thus archived include the subject identification list and signed subject 
ICFs. If archiving of the investigator site file is no longer possible at the site, the investigator 
must notify the Sponsor. 
All original subject files (medical records) must be stored at the site (hospital, research institute, 
or practice) for the longest possible time permitted by applicable regulations, and/or as per ICH 
GCP guidelines, whichever is longer. In any case, the investigator should ensure that no 
destruction of medical records is performed without the Sponsor’s written approval. 
11.6. 
Monitoring, Quality Assurance and Inspection by Health Authorities 
This trial will be monitored in accordance with the current version of the ICH Good Clinical 
Practice guideline (ICH E6). The site monitor will visit the trial site at regular intervals. 
Representatives of the Sponsor’s quality assurance unit or a designated organization, as well as 
health authorities, must be permitted to inspect all trial-related documents and other materials at 
the site, including investigator site file, completed eCRFs, ICFs, and the subjects’ original 
medical records/files. 

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The clinical trial protocol, data capture procedures, and data handling, including final clinical 
trial report, will be subject to independent quality assurance activities. Audits may be conducted 
at any time during or after the trial to ensure the validity and integrity of trial data. 
11.7. 
Publication Policy 
11.7.1. 
Clinical Trial Report 
After completion of the trial, a clinical trial report according to ICH E3 guideline will be written 
by the Sponsor or designated CRO in consultation with the Principal Investigator. 
11.7.2. 
Publications 
All information provided regarding the trial, as well as all information collected/documented 
during the course of the trial, will be regarded as confidential. The Sponsor reserves the right to 
release literature publications based on the results of the trial. Results from the trial will be 
published/presented as per the Sponsor’s publication strategy. 
Inclusion of the Investigator in the authorship of any multi-center publication will be based upon 
substantial contribution to the design, analysis, interpretation of data, drafting and/or critically 
revising any manuscript(s) derived from the trial. The investigator acknowledges that the trial is 
part of a multi-center trial and agrees that any publication by the investigator of the results of the 
trial conducted at his/her research site shall not be made before the first multi-center publication. 
In the event, there is no multi-center publication within 15 months after the trial has been 
completed or terminated at all trial sites, and all data has been received, the investigator shall 
have the right to publish its results from the trial, subject to the notice requirements described 
herein and subject to acknowledgement of the Sponsor as appropriate. The investigator shall 
provide the Sponsor 30 days to review a manuscript or any poster presentation, abstract or other 
written or oral material that describes the results of the trial for the purpose only of determining 
if any confidential or patentable information is disclosed thereby. If the Sponsor requests in 
writing, the investigator shall withhold any publication or presentation an additional 60 days 
solely to permit the Sponsor to seek patent protection. 
 
 

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12. 
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APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE SCALE 
ECOG Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about 
>50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair >50% of waking hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead. 
Source:  Oken MM, Creech RH, Tormey DC, et al. 1982. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 5(6):649–655. 
 
 

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APPENDIX 2. SIGNATURE PAGES AND RESPONSIBLE PERSONS 
FOR THE TRIAL 
 
 
 

 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
   
 
 
 
 
 
 
 
 
 
 
 

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Signature Page – Principal Investigator 
Title 
A Phase 1 / 2, Open-Label, Multiple Ascending Dose Trial to 
Investigate the Safety, Tolerability, Pharmacokinetics, 
Biological, and Clinical Activity of AGEN2034 in Subjects 
with Metastatic or Locally Advanced Solid Tumors, with 
Expansion to Second Line Cervical Cancer 
Clinical Trial Version / Date 
Version 6.0, 27 September 2019 
Center Number 
 
Principal Investigator 
 
 
I, the undersigned, am responsible for the conduct of the trial at this site and affirm that: 
• 
I understand and will conduct the trial according to the clinical trial protocol, and the 
approved protocol amendments; the current version of the Declaration of Helsinki Ethical 
Principles for Medical Research Involving Human Subjects), ICH Good Clinical Practice 
(ICH E6 guideline) as adopted by the applicable Health Authority requirements and national 
and state laws. 
• 
I will not deviate from the clinical trial protocol without prior written permission from the 
Sponsor, and prior review and written approval from the Institutional Review Board or 
Independent Ethics Committee, except where necessary to prevent immediate danger to the 
subject. 
I understand that some regulatory health authorities require the Sponsors of clinical trials to obtain and 
supply, when required, details about the investigators’ ownership interests in the Sponsor or 
investigational medicinal product and information regarding any financial ties with the Sponsor. The 
Sponsor will use any such information that is collected solely for the purpose of complying with the 
regulatory requirements. I therefore agree to supply the Sponsor with any necessary information regarding 
ownership interest and financial ties (including those of my spouse and dependent children), and to 
provide updates as necessary. 
 
 
 
 
Signature 
 
Date of Signature 
 
Name, academic degree 
 
Position (job title) 
 
Institution 
 
Address 
 
Telephone number 
 
E-mail address