Clinical trial NCT02266147
Conditions: B-cell Lymphoma
Keywords: Low Grade B-cell Lymphoma
Sponsor: Dynavax Technologies Corporation
Start date: 2014-10-01; Completion date: 2017-04-01
Enrollment: 29 participants; Allocation: ; Intervention model: SEQUENTIAL

Brief summary:
To assess the safety and tolerability of escalating doses of SD-101 in combination with localized low-dose radiation therapy in adult subjects with untreated low-grade B-cell lymphoma.

Detailed description:

Arms: arm 1: PART 1

* Radiation: 2 fractions of 2 Gy over 2 days at Days -1 and 1
* COHORT 1: 1 mg/mL at Days 1, 8, 15, 22, and 29
* COHORT 2: 2 mg/mL at Days 1, 8, 15, 22, and 29
* COHORT 3: 4 mg/mL at Days 1, 8, 15, 22, and 29
* COHORT 4: 8 mg/mL at Days 1, 8, 15, 22, and 29

PART 2

Cycle 1: Required

* Radiation: 2 fractions of 2 Gy over 2 days at Days -1 and 1
* COHORT 1: 1 mg/mL at Days 1, 8, 15, 22, and 29
* COHORT 2: 8 mg/mL at Days 1, 8, 15, 22, and 29

Cycle 2: Optional

* Radiation: 2 fractions of 2 Gy over 2 days at Days 180 and 181
* COHORT 1: 1 mg/mL at Days 181, 188, 195, 202, and 209
* COHORT 2: 8 mg/mL at Days 181, 188, 195, 202, and 209
Interventions: intervention 1: SD-101 intervention 2: Radiation therapy
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
Sponsor: Dynavax Technologies
Protocol Identifier: DV3-LYM-01
Protocol Title: A Phase 1/2, Non-randomized, Open-label, Multicenter, Dose Escalation and 
Expansion Study of Intratumoral Injections of SD-101 in Combination With Localized Low-dose 
Radiation in Patients With Untreated Low-grade B-cell Lymphoma
Document: Protocol Amendment 4.0
Document Date: 21 Mar 2016
NCT #: NCT02266147


Dynavax Technologies Corporation 
Protocol DV3-LYM-01 
SD-101 
Amendment #4 
CONFIDENTIAL AND PROPRIETARY 
Page 1 of 84 
Protocol Title: 
A Phase 1/2, Non-randomized, Open-label, 
Multicenter, Dose Escalation and Expansion Study 
of Intratumoral Injections of SD-101 in 
Combination With Localized Low-dose Radiation 
in Patients With Untreated Low-grade B-cell 
Lymphoma 
Protocol No.: 
DV3-LYM-01 
Investigational Product: 
SD-101 
US IND No.: 
122809 
Study Phase 
Phase 1/2 
Sponsor: 
Dynavax Technologies Corporation 
2929 Seventh Street, Suite 100 
Berkeley, CA  94710 
United States of America 
Medical Monitor: 
Craig Berman, MD, Medical Monitor 
Dynavax Technologies Corporation 
Tel:  (510) 665- 0451 Fax:  (510) 848-1327 
E-mail:  cberman@dynavax.com
Clinical Operations: 
Marissa Ramirez 
Associate Director, Clinical Operations 
Dynavax Technologies Corporation 
Tel:  +1 510 665-4626 Fax:  +1 510 848-9750 
E-mail:  mramirez@dynavax.com
Principal/Coordinating 
Investigator:
Ronald Levy, MD 
Professor of Medicine 
Division of Oncology 
Stanford Medical Center 
269 Campus Drive, CCSR 1105 
Stanford, CA 94305 
E-mail:  levy@stanford.edu
Original Protocol: 
Amendment #1: 
Amendment #2: 
Amendment #3: 
Amendment #4: 
08 May 2014 
24 June 2014 
10 April 2015 
05 November 2015 
21 March 2016 
This study will be conducted in accordance with good clinical practice (GCP) as defined in International 
Conference on Harmonisation (ICH) guidelines and applicable local legal and regulatory requirements. 




Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 3 of 84 
INVESTIGATOR SIGNATURE PAGE 
Protocol Title: A Phase 1/2, Non-randomized, Open-label, Multicenter, Dose 
Escalation and Expansion Study of Intratumoral Injections of SD-
101 in Combination With Localized Low-dose Radiation in 
Patients With Untreated Low-grade B-cell Lymphoma 
Protocol No.: DV3-LYM-01 
Original Protocol: 
Amendment #1: 
Amendment #2: 
Amendment #3: 
Amendment #4: 
08 May 2014 
24 June 2014 
10 April 2015 
05 November 2015 
21 March 2016 
Sponsor: Dynavax Technologies Corporation 
2929 Seventh Street, Suite 100 
Berkeley, CA 94710 
United States of America 
 
DECLARATION OF INVESTIGATOR 
I confirm that I have read and understood this protocol, and agree to conduct the study as 
outlined in the protocol and other information supplied to me. I agree to conduct the study in 
accordance with good clinical practice (GCP) as defined in International Conference on 
Harmonisation (ICH) guidelines and applicable local legal and regulatory requirements. 
 
 
Investigator Signature 
 
 
 
 
 
Date 
Investigator Name (Print) 
 
 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 4 of 84 
TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES .........................................................................................................................7 
LIST OF FIGURES .......................................................................................................................7 
LIST OF APPENDICES ...............................................................................................................7 
PROTOCOL SYNOPSIS ..............................................................................................................9 
1.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..............................18 
2.0 
INTRODUCTION AND RATIONALE .........................................................................20 
2.1 
Background ............................................................................................................20 
2.2 
Oligodeoxynucleotides With Cytosine Phosphoguanosine (CpG) Motifs ............21 
2.3 
Combined Radiotherapy and Intratumoral CpG-ODN Treatment of 
Lymphoma .............................................................................................................21 
2.4 
Clinical Experience With SD-101 .........................................................................22 
2.5 
Study Rationale and Doses to be Evaluated ..........................................................23 
3.0 
STUDY OBJECTIVES ....................................................................................................25 
3.1 
Primary Objectives.................................................................................................25 
3.2 
Secondary Objectives.............................................................................................25 
3.3 
Exploratory Objectives ..........................................................................................25 
4.0 
INVESTIGATIONAL PLAN .........................................................................................25 
4.1 
Study Design ..........................................................................................................25 
4.2 
Parts of Study .........................................................................................................27 
4.2.1 
Part 1:  Dose Escalation ........................................................................27 
4.2.2 
Part 2:  Expansion .................................................................................28 
4.3 
Duration of Study ...................................................................................................29 
4.4 
Study Endpoints .....................................................................................................29 
4.4.1 
Primary Endpoints .................................................................................29 
4.4.2 
Secondary Endpoints .............................................................................29 
4.4.3 
Exploratory Endpoints ..........................................................................29 
4.5 
Randomization .......................................................................................................29 
4.6 
Blinding..................................................................................................................29 
4.7 
Appropriateness of Measurements .........................................................................30 
4.8 
Study Termination .................................................................................................30 
5.0 
SELECTION OF SUBJECTS ........................................................................................30 
5.1 
Inclusion Criteria ...................................................................................................31 
5.2 
Exclusion Criteria ..................................................................................................32 
5.3 
Definition of Women of Childbearing Potential ....................................................33 


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
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5.4 
Removal of Subjects From Study ..........................................................................33 
6.0 
STUDY MATERIALS AND SUPPLIES .......................................................................34 
6.1 
Low-dose Radiation Therapy .................................................................................34 
6.2 
SD-101 ...................................................................................................................34 
6.2.1 
Investigational Medicinal Product ........................................................34 
6.2.2 
Instructions for Administration .............................................................34 
6.2.3 
Labeling.................................................................................................36 
6.2.4 
Storage and Handling Instructions ........................................................36 
6.2.5 
Control and Accountability of Investigational Medicinal Product .......36 
6.2.6 
Treatment Compliance ..........................................................................37 
7.0 
TREATMENT OF SUBJECTS ......................................................................................37 
7.1 
Treatment Administered ........................................................................................37 
7.2 
Treatment Period ....................................................................................................38 
7.3 
Treatment Precaution .............................................................................................38 
7.4 
Prohibited Treatments or Therapies .......................................................................38 
7.5 
Permitted Therapy ..................................................................................................39 
8.0 
ASSESSMENT OF RESPONSE ....................................................................................40 
8.1 
Interferon-inducible Genes ....................................................................................40 
8.2 
RNA Analysis ........................................................................................................40 
8.3 
Biomarker Analysis ...............................................................................................40 
8.4 
Response Evaluation and Criteria ..........................................................................41 
9.0 
MANAGEMENT OF STUDY TREATMENT TOXICITIES .....................................42 
9.1 
Dose-limiting Toxicity and Stopping Rules ..........................................................42 
9.2 
Dose Modification for Adverse Events..................................................................43 
9.3 
Reasons for Stopping a Subject From Receiving Additional Injections................44 
9.4 
Management of Subject Safety ..............................................................................44 
9.5 
Pre-Treatment Prophylaxis and Post-Treatment ....................................................45 
10.0 
TRIAL ASSESSMENTS .................................................................................................45 
10.1 
Informed Consent and Screening Log ...................................................................45 
10.2 
Screening Assessments ..........................................................................................46 
10.3 
Cycle 2 Treatment ..................................................................................................46 
10.4 
Safety Assessments ................................................................................................47 
10.4.1 
Medical and Medication History ...........................................................47 
10.4.2 
Vital Signs .............................................................................................47 
10.4.3 
Physical Examinations ..........................................................................47 
10.4.4 
Electrocardiogram .................................................................................48 


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SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
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10.4.5 
Safety Laboratory Assessments ............................................................48 
10.4.6 
Injection-site Reaction Assessments .....................................................49 
10.4.7 
Adverse Events......................................................................................49 
10.4.8 
Serious Adverse Events.........................................................................49 
10.4.9 
Concomitant Medications .....................................................................49 
10.5 
Disease Assessments ..............................................................................................50 
10.6 
Pharmacokinetic Assessments ...............................................................................50 
10.7 
Pharmacodynamic Assessments ............................................................................50 
10.8 
Immunogenicity Assessment .................................................................................51 
10.9 
Fine Needle Aspirate of Tumor Lesions ................................................................51 
10.10 Unscheduled Visit ..................................................................................................51 
10.11 Early Discontinuation Visit ....................................................................................52 
11.0 
REPORTING AND DOCUMENTATION OF ADVERSE EVENTS ........................52 
11.1 
Investigator’s Responsibilities ...............................................................................52 
11.2 
Injection-site Reactions ..........................................................................................52 
11.3 
Adverse Events ......................................................................................................53 
11.3.1 
Definition of Adverse Reaction ............................................................54 
11.3.2 
Definition of Suspected Adverse Reaction ...........................................54 
11.3.3 
Definition of Unexpected Adverse Event or Suspected Adverse 
Reactions ...............................................................................................54 
11.4 
Serious Adverse Events .........................................................................................54 
11.4.1 
Definition of Serious Adverse Events ...................................................54 
11.4.2 
Serious Adverse Event Reporting Requirements ..................................55 
11.5 
Adverse Event Severity and Relationship to Study Treatment ..............................56 
11.5.1 
Severity Grading of Adverse Events .....................................................56 
11.5.2 
Relationship of Adverse Events to Study Treatment ............................57 
11.6 
Reporting and Documentation of Pregnancy .........................................................57 
12.0 
STATISTICAL METHODS ...........................................................................................58 
12.1 
General ...................................................................................................................58 
12.2 
Sample-size Considerations ...................................................................................59 
12.3 
Study Analysis Populations ...................................................................................59 
12.4 
Demographic and Baseline Characteristics ...........................................................59 
12.5 
Pharmacokinetic and Pharmacodynamic Analyses ...............................................60 
12.6 
Safety Analyses ......................................................................................................60 
12.7 
Response Analyses.................................................................................................60 
12.8 
Interim Analysis .....................................................................................................60 


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 7 of 84 
13.0 
STUDY DOCUMENTATION AND DIRECT ACCESS .............................................61 
13.1 
Source Documents .................................................................................................61 
13.2 
Direct Access to Source Data/Documents .............................................................61 
14.0 
DATA QUALITY ASSURANCE ...................................................................................62 
15.0 
ETHICS ............................................................................................................................62 
15.1 
Institutional Review Board/Independent Ethics Committee..................................62 
15.2 
Ethical Conduct of the Study .................................................................................62 
15.3 
Informed Consent...................................................................................................62 
15.4 
Subject Confidentiality ..........................................................................................63 
16.0 
DATA HANDLING AND RECORD KEEPING ..........................................................63 
16.1 
Case Report Forms .................................................................................................63 
16.2 
Data Handling ........................................................................................................63 
16.3 
Coding of Adverse Events, Drugs, and Diseases ...................................................64 
16.4 
Record Retention ...................................................................................................64 
17.0 
USE OF INFORMATION AND PUBLICATION........................................................64 
18.0 
REFERENCES .................................................................................................................66 
 
LIST OF TABLES 
Table 8-1: 
Response Criteria for Non-Hodgkin’s Lymphoma ....................................42 
Table 11-1: 
Common Terminology Criteria for Adverse Events (CTCAE, Version 
4.03) ...........................................................................................................56 
Table 11-2: 
Definitions for Relationship of Adverse Events to Study Treatment ........57 
Table 12-1: 
Probabilities of Detecting Response ..........................................................59 
 
LIST OF FIGURES 
Figure 4-1: 
Study Flow Diagram – Dose Escalation (Part 1) .......................................27 
Figure 4-2: 
Study Flow Diagram – Dose Expansion (Part 2) .......................................27 
 
LIST OF APPENDICES 
Appendix 1: 
SCHEDULE OF STUDY ASSESSMENTS (PART 1 ONLY) ................69 
Appendix 2: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS 
UNDERGOING 1 TREATMENT CYCLE) .............................................73 
Appendix 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS 
UNDERGOING 2 TREATMENT CYCLES) ...........................................77 
Appendix 4: 
RESPONSE DEFINITIONS FOR CLINICAL TRIALS ..........................82 


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 8 of 84 
Appendix 5: 
ECOG PERFORMANCE STATUS INDEX.............................................83 
Appendix 6: 
TOXICITY GRADING SCALE FOR HEALTHY ADULT AND 
ADOLESCENT VOLUNTEERS ENROLLED IN PREVENTIVE 
VACCINE CLINICAL TRIALS ...............................................................84 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 9 of 84 
PROTOCOL SYNOPSIS 
Objectives: 
Primary Objectives: 
• 
To assess the safety and tolerability of escalating doses of SD-101 in 
combination with localized low-dose radiation therapy (XRT) in subjects 
with untreated low-grade B-cell lymphoma 
• 
To evaluate the pharmacodynamic (PD) profile of interferon (IFN)-inducible 
genes in whole blood 24 hours after intratumoral injection of SD-101 
• 
To determine the Maximum Tolerated Dose (MTD) or Optimal Dose of 
intratumoral SD-101 in combination with localized low-dose XRT 
Secondary Objectives: 
• 
To evaluate the plasma pharmacokinetics (PK) of SD-101 
• 
To assess the preliminary response both locally and systemically 
• 
Tumor shrinkage of the treated lesion(s) (Local) 
• 
Tumor shrinkage outside the treated lesion(s) (Systemic) 
Exploratory Objective: 
• 
To estimate the duration of tumor response both locally and systemically 
Study Design: 
This is a phase 1/2, non-randomized, open-label, multicenter, dose-escalation, 
and expansion study designed to evaluate the safety and preliminary efficacy of 
localized low-dose XRT and intratumoral SD-101 injection into a single target 
lesion (denoted as “Lesion A” in Treatment Cycle 1) in subjects with untreated 
low-grade B-cell lymphomas who do not require immediate systemic therapy and 
are appropriate candidates for “watch and wait”. 
In this protocol, treated lesion(s) is lesion(s) treated with XRT and SD-101; 
untreated lesion(s) is lesion(s) not treated with XRT and SD-101. 
“Lesion A” is the lesion identified to be treated with both XRT and SD-101. 
Additionally, at least 1 (up to 5) additional lesion(s) that is untreated and outside 
the field of radiation of “Lesion A” will be recorded and followed per Cheson 
criteria (1999) in Cycle 1. 
This study will be conducted in 2 parts:  Part 1 (Dose Escalation) which includes 
the evaluation of 4 escalating dose levels, and Part 2 (Expansion) which includes 
enrollment of up to 18 total subjects (9 per cohort) into a 1 mg and 8 mg SD-101 
dose cohort. Subjects enrolled in Part 2 with at least stable disease assessed by 
Cheson criteria for untreated lesions (excluding Lesion A) on Day 180 imaging 
and who meet all retreatment criteria will be treated with a second cycle of low 
dose radiation and SD-101. By default, the same lesion (Lesion A) treated in 
Cycle 1 should be retreated in Cycle 2. If Lesion A has entirely regressed by the 
time a subject is eligible for retreatment, then another pre-identified lesion (from 
Cycle 1) may be selected for treatment. 
Subjects in Part 2 will be required to complete imaging, laboratory and fine 
needle aspiration (FNA) of tumors as outlined in the Schedule of Study 
Assessments. FNA sampling requirement for Part 2 is 2 FNA samples each in 
both a treated and untreated lesion in Part 2 Cycle 1. FNA sampling requirement 
for Part 2 Cycle 2 is 1 FNA sample in both a treated and untreated lesion. For 
Part 2, Cycle 2, if a second untreated lesion is not available or accessible, an 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 10 of 84 
FNA sample collection of this second untreated lesion is not required. 
Imaging for the study is at Screening, and Days 90, 180, 360, 540 and 720. 
Subjects who undergo retreatment at Day 180 will have additional imaging at 
Day 270. 
FNA biopsy samples will be tested for both ribonucleic acid (RNA) expression by 
NanoString analysis and quantification of immunologic cellular infiltrates by 
flow cytometry during Cycle 1 and RNA expression by NanoString analysis for 
Cycle 2. 
Safety reporting periods is from initiation of study treatment until Day 90 post 
initiation of study treatment for both treatment cycles (Day 1-90 in Cycle 1 and 
Day 180-270 in Cycle 2). 
 
 
Part 1:  Dose Escalation 
Part 1 is a dose-ranging study using a standard 3 + 3 study design. The starting 
dose of SD-101 will be 1 mg administered intratumorally and will be given to a 
cohort of 3 subjects. If no Dose-limiting Toxicity (DLT) is observed in the first 
Follow-up
D -30 …
D -2
D -1
D8 D15 D22 D29 D36 … D720
↑
↑
↑
↑
↑
↑
↑
D = day.
a   Lesion A is one site of disease and is the same site throughout the study.
Assess 
response 
to Lesion A 
and 
outside of 
Lesion A
Part 1 - Dose Escalation 
Untreated low-
grade Lymphoma 
subjects with at 
least 2 sites of 
measurable 
disease
Low dose 
radiation to 
Lesion Aa
(2 doses)
SD-101
Intratumoral injection 
into Lesion Aa
 (5 doses)
D1
Screening
Treatment - Cycle 1
Patients Undergoing 1 
Treatment Cycle:
Patients Undergoing 2 
Treatment Cycles:
D -30 …
D -2
D -1
D8 D15 D22 D29 D36
D90
D180
D188 D195 D202 D209 D216 … D720
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
D = day.
a  Lesion A is one site of disease and is the same site throughout the study.
b  Imaging is Screening, Day 90, Day 180, Day 270, Day 360, Day 540, and Day 720
c  This lesion may be different than Lesion A from Cycle 1, must meet size requirements per Inclusion #2, and remain the same lesion 
throughout Treatment-Cycle 2.  
Follow-up
Screening
Treatment - Cycle 1
Part 2: Dose Expansion 
Untreated low-
grade Lymphoma 
subjects with at 
least 2 sites of 
measurable 
disease
Follow-up
Screening
Treatment - Cycle 1
Treatment - Cycle 2
Follow-up
D181
Low dose 
radiation to 
a lesionc
(2 doses)
Assess 
response to 
treated and 
non-treated 
lesions
D1
SD-101
Intratumoral injection 
into Lesion Aa
 (5 doses)
Low dose 
radiation to 
Lesion Aa
(2 doses)
SD-101
Intratumoral injection into a 
lesionc
 (5 doses)
Assess 
response to 
Lesion A 
and outside 
of Lesion Ab


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 11 of 84 
3 subjects, the next cohort will be enrolled and escalation will proceed to the next 
highest dose. If a DLT is observed in 1 subject in a cohort, enrollment will 
proceed and the cohort size will be increased up to 6 subjects. If only 1 DLT is 
observed in 6 subjects in a cohort, escalation will proceed and the next cohort 
may begin enrollment. However, if ≥ 2 of 6 subjects experience a DLT in any 
cohort, dose escalation will cease and the previous lower dose of SD-101 will be 
designated the MTD unless an intermediate dose is chosen to be studied to define 
the MTD. 
The dose cohorts for SD-101 are 1 mg, 2 mg, 4 mg, and 8 mg. If an MTD is not 
identified, dosing will stop at 8 mg. Decisions to escalate the dose of SD-101 to 
the next highest level will be based on review of safety data from the time of the 
first injection (Day 1 [Visit 2]) through 7 days following the last injection (Day 
36 [Visit 8]). Intra-subject dose escalation is not permitted. 
An Optimal Dose may be selected based on all available data including an 
assessment of IFN-inducible genes and tolerability data. Based on this 
evaluation, the Medical Monitor and investigators may choose an intermediate 
dose instead of the MTD. 
Treatment will consist of local radiation given over 2 days (Day -1 [Visit 1] and 
Day 1 [Visit 2]) (2 Gray [Gy] each day) followed by 5 weekly intratumoral 
injections with SD-101 on Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 5), Day 
22 (Visit 6), and Day 29 (Visit 7). 
Each subject will receive intratumoral injections to Lesion A (same site 
throughout dose escalation). If at any point during the treatment Lesion A has 
completely regressed, remaining injections will be given by subcutaneous 
injection into the site of Lesion A. 
Part 2:  Expansion 
Based on review of safety data in Part 1 (14 September 2015), no DLT or MTD 
was reported upon completion of dose escalation for the 1 mg, 2 mg, 4 mg, and 8 
mg SD-101 dosing cohorts. Subjects will be enrolled in Part 2 at 2 dose cohorts 
(1 mg and 8 mg) in order to better assess the safety and preliminary efficacy of 
SD-101. Eighteen subjects (9 per cohort) will be assigned to either a 1 mg or 8 
mg SD-101 dose cohort. The dosing schedule for the first cycle of SD-101 
treatment will be the same for both Parts 1 and 2 of the study. 
In addition, subjects in Part 2 will have the option to undergo a second cycle of 
localized low-dose radiation and SD-101 treatment (Cycle 2) at the last dose 
level that they received during Part 2 Cycle 1. Eligible subjects to receive 
Cycle 2 SD-101 treatment are required to have at least stable disease assessed by 
Cheson criteria for all Cycle 1 untreated lesions (excluding Lesion A) on 
Day 180 imaging, have at least one site of measurable and accessible disease (per 
Cheson criteria 1999) that can be injected, and meet all laboratory and other 
eligibility criteria (described in Section 10.3). All subjects who undergo 
retreatment with localized low-dose radiation and SD-101 at Day 180 will 
complete follow-up procedures as outlined in Appendix 3. If a subject does not 
consent to be retreated with localized low-dose radiation and SD-101 at Day 180, 
the subject will continue on study and complete follow-up procedures as outlined 
in Appendix 2. 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
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If during the enrollment of the expansion cohort, the type and duration of adverse 
events (AEs) suggests that the MTD has been exceeded, any remaining accrual to 
that cohort will be temporarily halted and available safety data will be reviewed 
and discussed with the investigators. A decision will then be made either to stop 
the study or to restart enrollment at a lower dose level.  
Study Population: 
The study population will include men and women with untreated low-grade B-
cell lymphoma with at least 2 measurable sites of disease, 1 of which must be 
accessible for intratumoral injection and a second tumor lesion that will not be 
included in the radiation field of the treated lesion. The study population must not 
be in immediate need for systemic therapy, and must be good candidates for 
“watch and wait”. 
Study Period: 
The total duration of subject participation in this study is up to 748 days. This 
includes a Screening period beginning up to 28 days prior to the first treatment, a 
30-day treatment period, and a follow-up period of up to 690 days. Optional:  an 
optional second 30-day treatment period starting at Day 180 and a follow-up 
period of up to 510 days for subjects who have consented to receive a second 
cycle of localized low-dose radiation and SD-101. 
Safety Evaluation: 
A number of measures will be taken to ensure the safety of subjects participating 
in this trial. These measures will be addressed through the review of 
Inclusion/Exclusion Criteria and routine safety monitoring, as indicated below. 
During active treatment, subjects will undergo targeted physical exams, 
electrocardiograms (ECGs), and laboratory assessments, which will include a 
complete blood count (CBC) with differential, platelet assessment, coagulation 
testing, and serum chemistry (including creatinine [Cr], liver function tests and 
lactate dehydrogenase [LDH]). 
Prior to each study injection, subjects will receive a new Diary Card with 
instructions to measure and record local injection-site reactions and solicited 
AEs. The completed Diary Cards will be reviewed with subjects at their next 
study visit. 
During the study follow-up period, safety will be evaluated through the careful 
monitoring of all clinical and laboratory AEs. Safety assessments will include 
ECG and specified laboratory parameters (eg, CBC, serum chemistry).  
Standard safety monitoring consistent with International Conference on 
Harmonisation (ICH) guidelines will be employed for DLT assessment and 
dose-escalation decisions during Part 1 (Dose Escalation). Before dose escalation 
at each dose level and at any other time that safety data warrant review during 
Cycle 1 or Cycle 2, as applicable, the coordinating principal investigator will 
participate in a teleconference with the Dynavax Medical Monitor and Contract 
Research Organization (CRO) Medical Monitor to review all safety data. 
 


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 13 of 84 
Other Assessments: 
All subjects will undergo safety assessments, tumor response determinations, 
and correlative biomarker testing performed at specified study visits, as indicated 
in Appendix 1, Appendix 2, and Appendix 3. 
Disease Assessment Prior to Treatment 
Once informed consent is obtained, baseline disease assessments will include: 
• 
Computerized Tomography (CT) scan of neck, chest, abdomen, pelvis, and 
other areas, as clinically indicated. Positron Emission Tomography (PET) 
scans will only be permitted if PET/CT is standard of care (SOC) at the 
participating institution and is performed instead of stand-alone CT. 
• 
Unilateral bone marrow biopsy and aspirate if not previously performed or if 
performed more than 90 days previously with negative results 
• 
Laboratory assessments 
• 
Copy of pathology report confirming diagnosis 
All subjects will be required to have Day 180 imaging and demonstrated stable 
disease, partial response (PR), or complete response (CR) (per Cheson criteria) 
and have at least one measurable and accessible target lesion (per palpation or 
ultrasound guidance) for SD-101 intratumoral injection in order to receive Cycle 
2 SD-101 treatment. Eligible subjects must provide consent prior to undergoing 
treatment in Cycle 2. 
Assessment of Disease Response to Treatment 
Disease assessment will include CT scans (or PET/CT) at 3 and 6 months after 
the first SD-101 injection, and then every 6 months for the remainder of the trial. 
For subjects who receive Cycle 2 XRT and SD-101 treatments, they will have an 
additional disease assessment (radiographic scans) at 9 months (Day 270) after 
the first SD-101 injection in Cycle 1. 
Response will be assessed by evaluating treated lesion (s) and all sites of 
untreated disease. 
Study Treatments: 
Treatments 
• 
Low-dose radiation (2 Gy × 2 doses) 
• 
SD-101 intratumoral injection 
Dosage and Administration 
Each subject in Part 1 will receive local XRT administered in 2 fractions of 2 Gy 
each for a total of 4 Gy over 2 days prior to and followed by 5 weekly 
intratumoral SD-101 injections to a single target lesion (denoted as “Lesion A”). 
The dosing schedule will be the same as Part 1 for Part 2. In addition, subjects in 
Part 2 will have the option to undergo a second cycle of localized low-dose 
radiation and SD-101 treatment (Cycle 2) at the last dose level that they received 
Part 2 Cycle 1. 
If at any point during treatment, the treated lesion has completely regressed, 
remaining injections will be given by subcutaneous injection into the site of the 
treated lesion. Retreatment at Day 180 (Cycle 2) may only be given to a lesion 
other than Lesion A if Lesion A has regressed and does not meet minimum size 


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requirement as described in the retreatment criteria or is otherwise approved by a 
Dynavax Medical Monitor. Once a lesion is selected, the same lesion must be 
injected for a given treatment cycle. 
The SD-101 doses planned for administration in the Part 1 dose escalation are 
1 mg, 2 mg, 4 mg, and 8 mg. SD-101 doses in Part 2 will be 1 mg and 8 mg. 
Intra-subject dose escalation is not permitted. For Part 2, dose interruptions 
(allowed for all subjects) may occur and rules for dose reductions (not allowed 
for subjects in the 1 mg dose cohort) are given in Section 9.0.  
Eligibility Criteria: 
Inclusion Criteria: 
A subject must meet all of the following criteria to be eligible for the study: 
1) Biopsy confirmed, untreated, low-grade B-cell lymphoma, including 
follicular (Grade 1, 2, or 3A) (Harris, Swerdlow et al. 2008), or marginal, or 
chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) 
with lymph node involvement 
2) At least 2 sites of measurable disease per Cheson criteria (must measure at 
least 1.5 cm in any diameter or 1.0 cm in the shortest diameter if one of the 
diameters is not ≥ 1.5 cm), 1 of which must be palpable and easily accessible 
in a low-risk site (eg, inguinal, axillary, cervical, subcutaneous) for 
intratumoral injection (denoted as “Lesion A” in Treatment Cycle 1) and at 
least one additional untreated lesion that is located outside the radiation field 
of the treated lesion (Lesion A) and is accessible for an FNA aspirate. 
3) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 
or 1 (Appendix 5) 
4) Aged 18 years and older 
5) Absolute neutrophil count (ANC) ≥1500/mm3 
6) Platelet count > 100,000/µL 
7) Serum Cr ≤ 1.5 × upper limit of normal (ULN) 
8) Serum total bilirubin ≤ 1.5 × the (ULN) 
9) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 
× ULN 
10) International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless 
subject is receiving anticoagulant therapy and PT or partial thromboplastin 
time (PTT) must be within the therapeutic range of intended use of 
anticoagulants 
11) Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant 
therapy, and the PT or PTT must be within the therapeutic range of intended 
use of anticoagulants. 


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12) Female subjects must have a negative urine or serum pregnancy test within 
72 hours prior to taking study medication if of childbearing potential as 
defined in this protocol. Women of childbearing potential (WOCBP) must be 
willing to use 2 medically acceptable methods of contraception from Day 1 
through 120 days after the last dose of trial treatment. The 2 medically 
acceptable birth control methods can be either 2 barrier methods or a barrier 
method plus a hormonal method to prevent pregnancy. The following are 
considered adequate barrier methods of contraception:  diaphragm, condom 
(by the partner), copper intrauterine device, sponge, or spermicide as per 
local regulations or guidelines. Appropriate hormonal contraceptives will 
include any registered and marketed contraceptive agent that contains an 
estrogen and/or a progestational agent (including oral, subcutaneous, 
intrauterine, or intramuscular agents). 
13) Ability to understand and sign informed consent form (ICF) and comply with 
treatment protocol 
Exclusion Criteria: 
A subject with any one of the following criteria is not eligible for the study: 
1) Diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy (including immune 
modulators or systemic corticosteroids) within 7 days prior to study 
enrollment 
2) Positive for hepatitis B (HBsAg reactive), hepatitis C (HCV RNA 
qualitative), or human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 
3) Diagnosis of mantle or diffuse large-cell lymphoma, Grade 3B follicular 
lymphoma (Harris, Swerdlow et al. 2008), or gastric mucosa-associated 
lymphoid tissue (MALT) lymphoma 
4) Clinically significant pleural effusion 
5) Active infection including cytomegalovirus 
6) Pregnant or breast feeding within the projected duration of trial participation 
through 4 months after the last dose of study treatment 
7) Autoimmune disease including systemic lupus erythematosus, rheumatoid 
arthritis, multiple sclerosis, Sjӧgren’s syndrome, autoimmune 
thrombocytopenia, history of uveitis, or other if clinically significant 
8) Lymphoma involvement of the central nervous system 
9) Received any prior therapy for lymphoma 
10) Use of any investigational agent within the last 28 days 


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11) Serious, non-healing wound, ulcer, or bone fracture 
12) If a subject received major surgery, must have recovered adequately from the 
toxicity and/or complications from the intervention prior to enrollment 
13) Clinically significant cardiovascular disease (eg, uncontrolled hypertension, 
myocardial infarction, unstable angina), New York Heart Association 
(NYHA) Grade II or greater congestive heart failure, serious cardiac 
arrhythmia requiring medication within 1 year prior to Day -1 (Visit 1); 
Grade II or greater peripheral vascular disease at study entry 
14) Any other significant medical or psychiatric condition, laboratory 
abnormality, or difficulty complying with protocol requirements that may 
increase the risk associated with study participation or study drug 
administration that may interfere with the interpretation of study results and, 
in the judgment of the investigator, would make the subject inappropriate for 
this study 
15) History of sensitivity to any component of SD-101 
16) A diagnosis of cancer within the last 3 years prior to enrollment or any 
known additional malignancy that is progressing or requires active treatment. 
Exceptions are B-cell lymphoma, basal cell carcinoma of the skin, squamous 
cell carcinoma of the skin that has undergone potentially curative therapy, 
and in situ cervical cancer. 
17) Is taking systemic corticosteroids (more than 3 consecutive days) or other 
immunomodulators or immune suppressive medication 
Study Endpoints 
Primary Endpoints  
• 
DLTs 
• 
Incidence of injection-site reactions, AEs and serious adverse events (SAEs) 
• 
Changes in IFN-inducible genes 
Secondary Endpoints 
• 
Plasma concentrations of SD-101 (Part 1 only) 
• 
Response rate of the treated lesion(s) according to Cheson criteria 
• 
Time to response of treated lesion(s) according to Cheson criteria 
• 
Response rate of untreated lesion(s) according to Cheson criteria 
• 
Time to response of untreated lesion(s) according to Cheson criteria 
Exploratory Endpoints 
• 
Duration of response of the treated lesion (s) according to Cheson criteria 
• 
Duration of response of untreated lesions according to Cheson criteria 
• 
Time to next treatment (TTNT) 
• 
Time to progression (TTP) 


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• 
Characterization of tumor infiltrating lymphocytes, co-stimulatory 
molecules, and other immune activated cells following SD-101 treatment  
Statistical Methods 
This trial is designed to allow preliminary assessments of safety and biological 
activity in approximately 25-31 subjects. No pre-specified hypothesis testing will 
be performed. All analyses of demographics, biological activity, and safety will 
be descriptive. 
A total of 13 subjects were enrolled in the Dose Escalation (Part 1) of the trial 
and approximately 18 subjects will be enrolled in Part 2. If the true response rate 
is 30%, a sample size of 12 subjects (per dose cohort) will have 74% chance to 
obtain 3 or more responders and 50% chance to obtain 4 or more responders. A 
90% exact binomial confidence interval will be constructed as preliminary 
efficacy information for further investigation. 
Table 12-1 details the probabilities of detecting the number of responses. AEs, 
SAEs, and abnormal laboratory values will be summarized by the proportion of 
subjects who experience them. 
PK and PD evaluations will assess changes in PK and PD parameters from before 
to after the second dose of SD-101. 
Response rate will be presented as the proportion of subjects who achieved CR or 
PR. Summary statistics will be provided for time to response, duration of 
response, TTP, and TTNT. 
 


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1.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation or Term 
Definition 
AE 
adverse event 
ALT 
alanine aminotransferase 
Anti-dsDNA 
antibodies to double-stranded deoxyribonucleic acid 
AST 
aspartate aminotransferase 
CBC 
complete blood count 
CLL 
chronic lymphocytic leukemia 
CpG 
cytosine phosphoguanosine  
Cr 
creatinine 
CFR 
Code of Federal Regulations 
CR 
complete response, complete remission 
CRF 
case report form 
CRO 
Contract Research Organization 
CT 
computerized tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic case report form 
ED 
early discontinuation 
EDC 
electronic data capture 
FDA 
United States Food and Drug Administration 
FLIPI 
follicular lymphoma international prognostic index 
FNA 
fine needle aspiration 
GCP 
good clinical practice 
Gy 
Gray, unit of radiation 
HCV 
hepatitis C virus 
Hgb 
hemoglobin 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 


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Abbreviation or Term 
Definition 
IFN 
interferon 
IMP 
investigational medicinal product 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
LDH 
lactate dehydrogenase 
MALT 
mucosa-associated lymphoid tissue  
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
Maximum Tolerated Dose 
NHL 
Non-Hodgkin’s lymphoma 
ODN 
oligodeoxynucleotide 
PD 
pharmacodynamics 
pDC 
plasmacytoid dendritic cell 
PET 
Positron Emission Tomography 
PK 
pharmacokinetics 
PR 
partial response, partial remission 
PS 
Performance Status 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAR 
suspected adverse reaction 
SLL 
small lymphocytic lymphoma 
SOC 
standard of care 
SPD 
sum of the products of greatest diameters 
SUSAR 
suspected unexpected serious adverse reaction 
TLR-9 
Toll-like receptor-9 
TTP 
time to progression 
TTNT 
time to next treatment 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
XRT 
radiation therapy 


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2.0 
INTRODUCTION AND RATIONALE 
2.1 
Background 
Non-Hodgkin’s lymphoma (NHL) is a group of histologically and perhaps biologically distinct 
lymphoid malignancies. Eighty to 90% of NHLs are B-cell lymphomas, and the great majority of 
the rest are T-cell lymphomas. Currently, NHL accounts for approximately 69,740 new cases per 
year, representing 4.2% of all cancers diagnosed in the United States, and 19,200 cancer deaths 
per year (National Cancer Institute 2014). Reporting from the US Surveillance, Epidemiology, 
and End Results (SEER) program indicates that the incidence of NHL has increased 0.5% per 
year for the past 10 years. 
NHLs encompass many histological types. The Revised European-American Classification of 
Lymphoid Neoplasms (REAL) developed in 1994 is the currently accepted classification of 
lymphoid neoplasms (Harris, Jaffe et al. 1994). This was further refined by the World Health 
Organization (WHO) classification of hematologic malignancies in 1997. Based on the WHO 
classification, NHLs are grouped into low-grade, aggressive, and highly aggressive lymphomas 
based on the clinical behavior of each entity. 
Low-grade lymphomas are subdivided into B-cell and T-cell types. The low-grade B-cell 
lymphomas include follicular lymphoma, B-chronic lymphocytic leukemia (CLL)/small 
lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma and marginal zone lymphoma. 
The T-cell group includes T-CLL and mycosis fungoides. 
All low-grade lymphomas share several common characteristics, including a relatively low-grade 
and prolonged clinical course, and a potential to transform to a more aggressive form of 
lymphoma. The tumor is often disseminated at diagnosis, and is rarely cured. Although the 
disease is sensitive to chemotherapy, radiotherapy, and immunotherapy, patients eventually 
exhaust all options and succumb to progression of disease. All low-grade B-cell lymphomas will 
be included in this trial. Follicular lymphoma is the major type of low-grade B-cell lymphoma, 
representing 13% of all NHLs. It has a prolonged clinical course and is not curable. The median 
survival of all patients with follicular lymphoma is at least 10 years. The prognosis of follicular 
lymphoma patients is largely determined by a constellation of clinical parameters, described as 
follicular lymphoma international prognostic index (FLIPI), determined at disease presentation 
(Solal-Celigny, Roy et al. 2004). FLIPI includes 1 “point” each for stage III/IV disease, number 
of nodal sites involved > 4, lactate dehydrogenase (LDH) > normal, age > 60 years, and 
hemoglobin (Hgb) < 12 gm/dL. Patients with 0 to 1, 2, or ≥ 3 risk factors belong to low-risk, 
intermediate, and poor risk groups, respectively. Follicular lymphoma is sensitive to many 
treatment modalities but the response is generally not durable and subjects eventually succumb 
to the disease. Therefore, novel therapies are needed to improve the outcome of subjects with 
follicular lymphoma and other low-grade B-cell lymphomas. 


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2.2 
Oligodeoxynucleotides With Cytosine Phosphoguanosine (CpG) Motifs 
Bacterial deoxyribonucleic acid (DNA) has long been recognized as having potent stimulatory 
effects on the immune system, including stimulating rejection of transplantable tumors in mice 
(Yamamoto, Kuramoto et al. 1988). This activity is mediated preferentially by specific DNA 
motifs containing a cytosine phosphoguanosine (CpG) dinucleotide and can be replicated by 
short synthetic oligodeoxynucleotides (CpG-ODN) (Kuramoto, Yano et al. 1992, Tokunaga, 
Yano et al. 1992, Roman, Martin-Orozco et al. 1997). CpG-ODNs stimulate specific immune 
cell types by activation of the innate recognition receptor, Toll-like receptor-9 (TLR-9) (Krieg 
2006), and have no activity in mice with a homozygous deletion of the TLR-9 gene (Campbell, 
Cho et al. 2009). 
Based on studies with cultured human peripheral blood mononuclear cells, CpG-ODNs can 
stimulate interferon (IFN)-alpha and interleukin-12 production as well as functional maturation 
in plasmacytoid dendritic cells (pDCs) (Duramad, Fearon et al. 2005) and can induce 
proliferation and immunoglobulin production in human B-cells (Krieg, Yi et al. 1995). Signaling 
by CpG-ODNs through TLR-9 requires active uptake of the ODN as TLR-9 is present only in 
specific intracellular compartments (Krieg 2002). TLR-9 signaling occurs in 2 distinct 
intracellular structures, early and late endosomes (Honda, Ohba et al. 2005, Guiducci, Ott et al. 
2006), leading to different outcomes. In pDCs, TLR-9 signaling in the early endosome leads to 
induction of type 1 IFNs, especially IFN-alpha, whereas signaling in late endosomes results in 
differentiation of pDCs to potent antigen-presenting cells. Differences in sequence and structure 
lead to different localization to these 2 intracellular compartments, allowing selection of CpG-
ODNs that stimulate low or high levels of type 1 IFNs (termed CpG-B and CpG-C class ODN, 
respectively). SD-101 belongs to the CpG-C class of CpG-ODN and was selected to stimulate 
very high levels on IFN-alpha as well as inducing maturation of pDC to antigen-presenting cells. 
Please refer to the Investigator’s Brochure for additional information on nonclinical testing. 
2.3 
Combined Radiotherapy and Intratumoral CpG-ODN Treatment of Lymphoma 
Radiation therapy (XRT) is being employed in this trial because tumor cells undergo cell death 
upon irradiation (Mirzaie-Joniani, Eriksson et al. 2002) causing the release of tumor antigens 
locally. These tumor antigens can be processed by antigen presenting cells to initiate a tumor-
specific immune response. Combination of XRT with intratumoral SD-101 may thus be able to 
boost the immunogenicity of the released antigens, promoting generation of a systemic, tumor-
specific immune response. 
In a number of different animal models, intratumoral injection of CpG-ODN has proven 
significantly more effective for tumor killing and generation of anti-tumor immunity than 
systemic administration (Kawarada, Ganss et al. 2001, Lou, Liu et al. 2011). Studies combining 
XRT and intratumoral CpG-ODN administration have shown efficacy in patients with indolent 
B-cell lymphomas (Brody, Ai et al. 2010) or cutaneous T-cell lymphoma (Kim, Gratzinger et al. 
2012). Regression of untreated tumor sites in a subset of patients provided evidence for 


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generation of anti-tumor immunity in each of these studies. These 2 studies, as well as virtually 
all other published studies of CpG-ODN treatment in cancer patients, were done with 
CpG-ODNs belonging to the CpG-B class, which induces significantly lower levels of type 1 
IFNs in humans than CpG-C class ODNs, such as SD-101. 
2.4 
Clinical Experience With SD-101 
In the phase 1, single-blind, dose-escalation study of SD-101 in 26 healthy normal male 
volunteers, aged 18 years and over (Study DV3-HNV-01), adverse events (AEs) included flu-
like symptoms such as headache, chills, fatigue, and pyrexia, as well as injection site reactions 
such as erythema, induration and pain. Dose-limiting toxicities (DLTs) of severe headache, 
injection site induration, and neck pain were observed in 1 subject given 5.0 mg of SD-101, 
resulting in a halt in dose escalation and accrual. Transient lymphopenia was the most common 
laboratory abnormality observed. There was no evidence of complement activation, coagulation 
abnormalities, auto-antibody development, or acute AE syndrome. 
In the phase 1 single-blind, dose-escalation study of SD-101 in 34 men and women, aged 18 to 
55 years, with chronic hepatitis C virus (HCV) infection, SD-101 was administered alone or in 
combination with ribavirin (Study DV3-HCV-01). Including doses up to 5 mg of SD-101, the 
majority of AEs were injection site reactions (erythema, swelling, pain, and pruritus), 
influenza-like illness, pyrexia, and myalgia. Most AEs were mild or moderate in reported 
severity. One subject in the SD-101 0.1 mg/ribavirin group experienced a serious adverse event 
(SAE) of hyperthyroidism that was considered probably related to SD-101 and unrelated to 
ribavirin. No deaths occurred during the study. 
In the phase 1b/2, open-label, multicenter, dose-escalation and expansion study, intratumoral 
SD-101 is being administered in combination with pembrolizumab in subjects with metastatic 
melanoma (Study DV3-MEL-01). As of 25 February 2016, 5 subjects have been enrolled and 
treated in Part 1 in the 2 mg SD-101 dose cohort. One subject permanently discontinued from the 
study at Day 22 due to disease progression. Further dose escalation and enrollment into the 4 mg 
and 8 mg SD-101 dose cohorts has not been initiated. No DLTs have been reported to date. The 
study is ongoing. 
A summary of the clinical studies conducted to date with SD-101 is provided in the 
Investigator’s Brochure. 
At the time of Protocol Amendment 4, for the current study (DV3-LYM-01), the DLT 
assessment period for all subjects in Part 1 has been completed and the study is ongoing with 
long term follow-up for subjects in Part 1 and planned enrollment of 18 subjects into Part 2, split 
evenly between 2 SD-101 dosing cohorts (1 mg and 8 mg). As of 25 February 2016, a total of 10 
subjects have been enrolled into Part 2 (6 at 1 mg and 4 at 8 mg). The decision for Part 2 SD-101 
dosing is described below. Of note, the data is preliminary and has not been fully monitored.  


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In Part 1 of this study, 13 subjects were enrolled and treated in 4 dose cohorts (1 mg, 2 mg, 4 mg, 
and 8 mg) with no DLTs reported. No determination of a Maximum Tolerated Dose (MTD) or 
optimal dose (for Part 2) was made. Three subjects were enrolled and treated in each of the 1 mg, 
2 mg, and 4 mg dose cohorts. Four subjects were enrolled and treated in the 8 mg cohort (1 
subject discontinued study treatment after one dose of SD-101 per subject decision for a Grade 2 
confusion that occurred secondary to fever and flu-like symptoms). Per preliminary data (study is 
ongoing), the primary toxicity observed from SD-101 was Grade 1 or 2 flu-like symptoms with 
onset 4 to 8 hours after SD-101 injection and resolved with symptomatic treatment. The most 
common laboratory abnormalities were transient decrease in neutrophils that occurred in some 
subjects and was more common in the 4 mg and 8 mg dose cohorts. One subject in the 8 mg dose 
cohort with a baseline Day 1 neutrophil count of 1390 cells/mm3 (etiology unknown) had 2 dose 
delays due to Grade 3 neutropenia which resolved in 10 to 11 days. There were no Grade 4 or 
higher AEs reported. Efficacy and pharmacodynamic/correlative translational data demonstrated 
a decrease in treated and overall tumor burden at the 1 mg, 2 mg, and 4 mg dose cohorts (8 mg 
efficacy data has not yet been obtained per protocol schedule and limited follow-up to date). The 
induction of IFN-alpha inducible genes was observed at all 4 dose levels without a substantial 
difference observed between the dose cohorts. The decision for dosing in Part 2 was to 
investigate both a low and higher SD-101 dose cohort (1 mg and 8 mg). Two subjects required a 
dose delay due to Grade 2 and Grade 3 neutropenia, respectively (both treated in the 1 mg dose 
cohort). There have been no reported Grade 4 or 5 events or SAEs reported for the Part 2 
subjects. The study is ongoing. 
The preliminary efficacy data from Part 1 (Cheson Criteria 1999) revealed a decrease in both 
treated and untreated disease. A reduction of the product of diameters in treated tumors occurred 
in 12 subjects (median -45.3%; range [-87, +100]) and in untreated tumors occurred in 11 
subjects (median -8.1%; range [-48, +45]). Induction of alpha-interferon genes, a surrogate for 
SD-101 activity, occurred at all dose levels with similar level of induction. At the treated site, 
regulatory T-cells (T Regs) were reduced in 8 of 10 subjects (average decrease 22.3 + 9.5%) at 
Day 8. There was an average reduction of 83.3 + 9.9% in follicular T helper cells (Tfh) at Day 8 
(n=9 with baseline Tfh). 
Five subjects in Part 1 discontinued due to disease progression (3 due to radiographic 
progression [1 each at 1, 2, and 4 mg], 1 due to increasing symptoms [abdominal pain] attributed 
to disease progression [2 mg], and 1 subject with CLL who had an increase in peripheral 
lymphocytes [4 mg]). One subject in Part 2 discontinued due to disease progression (1 mg dose 
cohort). All other subjects are ongoing. 
2.5 
Study Rationale and Doses to be Evaluated 
This open-label, dose-ranging, multicenter study was designed to evaluate the safety and 
preliminary efficacy of localized low-dose XRT and intratumoral injection of SD-101 for the 
treatment of untreated low-grade B-cell lymphoma. The hypothesis to be tested in this study is 
that SD-101, by virtue of its potency and its ability to induce high levels of IFN, will have 


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meaningful efficacy in generating antitumor immune responses when combined with XRT. IFNs 
have multiple effects on both the tumor cells and the tumor infiltrating leukocytes. IFNs can 
directly inhibit the proliferation of tumor cells and increase major histocompatibility complex 
class I expression, enhancing antigen recognition. Additionally IFNs have potent effects on 
tumor infiltrating leukocytes, including enhancing antigen presenting function of dendritic cells, 
increasing the effector function of T-cells, and activating cytotoxic activity of natural killer cells 
(Hervas-Stubbs, Perez-Gracia et al. 2011). 
The population to be studied will be subjects with untreated low-grade B-cell lymphomas who 
do not require immediate systemic therapy and are appropriate candidates for “watch and wait”. 
Treatment in Part 1 consists of 1 cycle of local radiation over 2 days (2 Gray [Gy] each day) 
followed by 5 weekly intratumoral injections of SD-101; doses of 1 mg, 2 mg, 4 mg, and 8 mg 
will be tested sequentially in a standard 3+3 study design. The dosing schedule is the same in 
Part 2, and in addition, subjects in Part 2 will have the option to undergo a second cycle of 
localized low-dose radiation and SD-101 treatment (Cycle 2) at the last dose level that they 
received in Part 2 Cycle 1. Subjects will be followed until next treatment or until approximately 
2 years after the first injection of SD-101. A key feature of this design is that the assessment of 
tumor regression will be done on one or more evaluable lesions that are neither irradiated nor 
injected with SD-101. The assumption is made that an effect on sites distal to the treated site 
provides evidence for generation of an effective systemic anti-tumor immune response. 
The SD-101 doses selected are based on previous clinical studies conducted with SD-101 
(DV3-HNV-01, DV3-HCV-01), the mechanism of action, and nonclinical studies with SD-101. 
Based on data from a study in healthy male volunteers (DV3-HNV-01), elevation of biomarkers 
was seen after a single 0.1 mg subcutaneous dose and increased with doses up to 5 mg. AEs were 
limited to flu-like symptoms and administration-site pain and induration. For further information, 
see the Investigator’s Brochure. 
The reason for choosing a low-dose radiation is that the low-dose therapy is sufficient to induce 
tumor cell death and will not jeopardize subjects’ opportunity to receive standard radiotherapy at 
the same anatomic site in the future. 
The rationale for choosing two doses to be explored in dose expansion (Part 2) is to obtain 
further safety and efficacy data to select a recommended Phase 2 dose. In Part 1, an MTD was 
not determined, activity was observed but not clearly different between dose cohorts, and 
induction of alpha-interferon gene expression was observed at all doses and did not differ 
significantly between dose cohorts. 
The rationale for adding a second cycle of localized low-dose XRT and SD-101 (Cycle 2 for 
subjects with at least stable disease assessed by Cheson criteria for untreated lesions [excluding 
Lesion A] on Day 180 imaging) is to allow further SD-101 treatment for those subjects who have 
demonstrated evidence of anti-tumor activity, have tolerated the initial study treatment cycle 
(Cycle 1) without having experienced a DLT, and are candidates for retreatment per 
safety-related eligibility criteria. Re-dosing to further stimulate an immune response is a general 


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immunologic strategy and will be assessed to potentially improve responses in this patient 
population. An anecdotal report of a patient further responding to retreatment with a TLR-9 
agonist (same target as SD-101) was reported by Brody 2010 (Brody, Ai et al. 2010). 
3.0 
STUDY OBJECTIVES 
3.1 
Primary Objectives 
• To assess the safety and tolerability of escalating doses of SD-101 in combination with 
localized low-dose XRT in subjects with untreated low-grade B-cell lymphoma 
• To evaluate the pharmacodynamic (PD) profile of IFN-inducible genes in whole blood 
24 hours after intratumoral injection of SD-101 
• To determine the MTD or Optimal Dose of intratumoral SD-101 in combination with 
localized low-dose XRT 
3.2 
Secondary Objectives 
• To evaluate the plasma pharmacokinetics (PK) of SD-101 
• To assess the preliminary response both locally and systemically 
• Tumor shrinkage of the treated lesion(s) (Local) 
• Tumor shrinkage outside the treated lesion(s) (Systemic) 
3.3 
Exploratory Objectives 
• To estimate the duration of tumor response both locally and systemically 
4.0 
INVESTIGATIONAL PLAN 
4.1 
Study Design 
This is a phase 1/2, non-randomized, open-label, multicenter, dose-escalation and expansion 
study designed to evaluate the safety and preliminary efficacy of localized low-dose XRT and 
intratumoral SD-101 injection into a single target lesion (denoted as “Lesion A” in Treatment 
Cycle 1) in subjects with untreated low-grade B-cell lymphomas who do not require systemic 
therapy and are appropriate candidates for “watch and wait”. 
In this protocol, treated lesion(s) is lesion(s) treated with XRT and SD-101; untreated lesion(s) is 
lesion(s) not treated with XRT and SD-101. 
“Lesion A” is the lesion identified to be treated with both XRT and SD-101. Additionally, at 
least 1 (up to 5) additional lesion(s) that is untreated and outside the field of radiation of “Lesion 
A” will be recorded and followed per Cheson criteria (1999) in Cycle 1. 
This study will be conducted in 2 parts (Study flow diagrams Figure 4-1 and Figure 4-2). Part 1 
(Dose Escalation) consists of the evaluation of 4 escalating dose levels, and Part 2 (Expansion), 


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Protocol DV3-LYM-01 
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CONFIDENTIAL AND PROPRIETARY 
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which includes enrollment of 18 total subjects (9 per cohort) into a 1 mg or 8 mg SD-101 dose 
cohort. 
Subjects in Part 2 will have the option to undergo a second cycle of localized low-dose radiation 
and SD-101 treatment (Cycle 2) at the last dose level that they received in Part 2 Cycle 1, once 
they meet eligibility as described in Section 10.3. During Part 2 Cycle 1, all subjects are required 
to have 2 fine needle aspiration (FNA) samples each from the treated lesion (Lesion A) and 
untreated lesion (Lesion B) that is located outside the radiation field of the treated lesion (Lesion 
A). During Part 2 Cycle 2, all subjects will be required to have only 1 FNA from the treated 
lesion, and an untreated lesion that is located outside the radiation field of the treated lesion. If 
no accessible untreated lesion is present on Day 180 imaging, then FNA is only required for the 
treated lesion. 
All subjects will undergo safety assessments, PK and PD assessments, tumor response 
determinations, and correlative biomarker testing performed at specified study visits, as indicated 
in the Schedule of Study Assessments (Appendix 1, Appendix 2, and Appendix 3). 
Once informed consent is obtained, baseline disease assessments will include: 
• Computerized tomography (CT) scan of neck, chest, abdomen, pelvis, and other areas, as 
clinically indicated. Positron Emission Tomography (PET) scans will only be permitted if 
PET/CT is the standard of care (SOC) at the participating institution. 
• Unilateral bone marrow biopsy and aspirate if not previously performed or if performed more 
than 90 days previously with negative results 
• Laboratory assessments 
• Copy of pathology report confirming diagnosis 
Disease assessment will include CT scans (or PET/CT) at 3 months (Day 90) and 6 months 
(Day 180) after the first study injection, and then every 6 months for the remainder of the trial. 
There is an additional CT scan at 9 months (Day 270) for subjects who are retreated at 6 months 
(Day 180) with a second cycle of localized low-dose radiation and SD-101. 
Response will be assessed by evaluating treated lesion(s) and all sites of disease outside of 
treated lesion(s). All untreated sites followed and recorded in the electronic case report form 
(eCRF) and used for assessment of disease response per Cheson criteria (1999) should be 
selected outside of the radiation field of the treated lesion.


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CONFIDENTIAL AND PROPRIETARY 
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Figure 4-1: 
Study Flow Diagram – Dose Escalation (Part 1) 
 
Figure 4-2: 
Study Flow Diagram – Dose Expansion (Part 2) 
 
4.2 
Parts of Study 
4.2.1 
Part 1:  Dose Escalation 
Part 1 is a dose-ranging study using a standard 3 + 3 study design. The starting dose of SD-101 
will be 1 mg administered intratumorally and will be given to a cohort of 3 subjects. 
If no DLT is observed (Section 9.1) in the first 3 subjects, the next cohort will be enrolled, and 
escalation will proceed to the next highest dose. 
Follow-up
D -30 …
D -2
D -1
D8 D15 D22 D29 D36 … D720
↑
↑
↑
↑
↑
↑
↑
D = day.
a   Lesion A is one site of disease and is the same site throughout the study.
Part 1 - Dose Escalation 
Untreated low-
grade Lymphoma 
subjects with at 
least 2 sites of 
measurable 
disease
Low dose 
radiation to 
Lesion Aa
(2 doses)
SD-101
Intratumoral injection 
into Lesion Aa
 (5 doses)
D1
Screening
Treatment - Cycle 1
Assess 
response to 
Lesion A 
and outside 
of Lesion A
Patients Undergoing 1 
Treatment Cycle:
Patients Undergoing 2 
Treatment Cycles:
D -30 …
D -2
D -1
D8 D15 D22 D29 D36
D90
D180
D188 D195 D202 D209 D216 … D720
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
↑
D = day.
a  Lesion A is one site of disease and is the same site throughout the study.
b  Imaging is Screening, Day 90, Day 180, Day 270, Day 360, Day 540, and Day 720
Assess 
response to 
treated and 
non-treated 
lesions
D1
SD-101
Intratumoral injection 
into Lesion Aa
 (5 doses)
Low dose 
radiation to 
Lesion Aa
(2 doses)
SD-101
Intratumoral injection into a 
lesionc
 (5 doses)
Assess 
response to 
Lesion A 
and outside 
of Lesion Ab
Treatment - Cycle 1
Treatment - Cycle 2
Follow-up
D181
Low dose 
radiation to 
a lesionc
(2 doses)
c  This lesion may be different than Lesion A from Cycle 1, must meet size requirements per Inclusion #2, and remain the same lesion 
throughout Treatment-Cycle 2.  
Follow-up
Screening
Treatment - Cycle 1
Part 2: Dose Expansion 
Untreated low-
grade Lymphoma 
subjects with at 
least 2 sites of 
measurable 
disease
Follow-up
Screening


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Protocol DV3-LYM-01 
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If a DLT is observed in 1 subject in a cohort, enrollment will proceed and the cohort size will be 
increased up to 6 subjects. 
If only 1 DLT is observed in 6 subjects in a cohort, escalation will proceed and the next cohort 
may begin enrollment. 
However, if ≥ 2 of 6 subjects experience a DLT in any cohort, dose escalation will cease and the 
previous lower dose of SD-101 will be designated the MTD unless an intermediate dose is 
chosen to be studied to define the MTD. 
The dose cohorts for SD-101 are 1 mg, 2 mg, 4 mg, and 8 mg. If an MTD is not identified, 
dosing will stop at 8 mg. Decisions to escalate the dose of SD-101 to the next highest level will 
be based on review of safety data from the time of the first injection (Day 1 [Visit 2]) through 7 
days following the last injection (Day 36 [Visit 8]). Intra-subject dose escalation is not permitted. 
An Optimal Dose may be selected based on all available data including an assessment of 
IFN-inducible genes and tolerability data. Based on this evaluation, the Medical Monitor and 
investigators may choose an intermediate dose instead of the MTD. 
4.2.2 
Part 2:  Expansion 
As discussed in Section 2.4, on completion of Part 1 dose escalation for all 4 planned cohorts (1, 
2, 4, and 8 mg) no DLT, no MTD, nor an Optimal Dose has been determined. As a result, Part 2 
dose expansion will be a dose range study with 2 cohorts (SD-101 at 1 mg and 8 mg). This part 
of the study will enroll 18 subjects (9 in the 1 mg cohort followed by 9 in the 8 mg cohort). The 
dosing schedule and imaging/tumor assessment will be the same for both parts of the study with 
the exception of changes described in Section 4.1. 
In addition, subjects in Part 2 will have the option to undergo a second cycle of treatment with 
localized low-dose XRT and SD-101 (Cycle 2) at the last dose level that they received during 
Part 2 Cycle 1. Part 2 procedures for subjects undergoing 1 treatment cycle and for subjects 
undergoing 2 treatment cycles are listed in the Schedule of Study Assessments Appendix 2 and 
Appendix 3, respectively. Localized low-dose radiation and SD-101 will be administered at the 
last dose level received in Part 2 Cycle 1 for a given subject. Of note, the treated lesions may be 
different between the first and second dosing cycles (in subjects who undergo repeat dosing at 
Day 180). The same lesion should be treated for a given Treatment Cycle. In order to receive 
retreatment at Day 180, subjects must meet all laboratory and eligibility criteria described in 
Section 10.3. 
If during the enrollment of the expansion cohort, the type and duration of AEs suggests that the 
MTD has been exceeded, any remaining accrual to that cohort will be temporarily halted and 
available safety data will be reviewed and discussed with the investigators. A decision will then 
be made either to close a cohort, stop the study, or to restart enrollment at a lower dose level. 


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4.3 
Duration of Study 
The total duration of subject participation in this study is up to 748 days for all subjects who 
enroll in this study. This includes a Screening period beginning up to 28 days prior to the first 
treatment, a 30-day treatment period, and a follow-up period of up to 690 days for all subjects in 
dose escalation (Part 1) and all subjects in dose expansion (Part 2) who do not receive 
retreatment at Day 180. For subjects undergoing Cycle 2 treatment, the second treatment period 
is 30 days (Day 180-Day 210) followed by a follow-up period of up to 510 days 
(Day 216-Day 720). 
4.4 
Study Endpoints 
4.4.1 
Primary Endpoints 
• DLTs 
• Incidence of injection-site reactions, AEs, and SAEs 
• Changes in IFN-inducible genes 
4.4.2 
Secondary Endpoints 
• Plasma concentrations of SD-101 (Part 1 only) 
• Response rate of treated lesion(s) according to Cheson criteria 
• Time to response of treated lesion(s) according to Cheson criteria 
• Response rate of untreated lesion(s) according to Cheson criteria 
• Time to response of untreated lesion(s) according to Cheson criteria 
4.4.3 
Exploratory Endpoints 
• Duration of response treated lesion(s) according to Cheson criteria 
• Duration of response outside of treated lesion(s) according to Cheson criteria 
• Time to next treatment (TTNT) 
• Time to progression (TTP) 
• Characterization of tumor infiltrating lymphocytes, co-stimulatory molecules, and other 
immune activated cells following SD-101 treatment 
4.5 
Randomization 
None of the subjects in this study will be randomized. 
4.6 
Blinding 
Blinding will not be performed as this is an open-label study. 


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4.7 
Appropriateness of Measurements 
The measure of response of lesions in this study is based on the Cheson criteria for low-grade 
B-cell lymphomas (Cheson, Horning et al. 1999, Cheson, Pfistner et al. 2007) (Appendix 4). This 
is the standard clinical trial assessment of tumor response in NHL clinical studies. The measures 
of safety in the study are routine clinical and laboratory procedures and assessment of AEs is 
adapted from the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 
(National Cancer Institute 2010) (Table 11-1). The measurement of injection site reactions (listed 
on the Diary Card) is based on the Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials (Center for Biologics Evaluation and 
Research 2007) (Appendix 6). 
4.8 
Study Termination 
The final study visit will occur when the last subjects completes the last study visit. The end-of-
study date is defined as the date of the last visit of the last participant. However, the sponsor 
reserves the right to terminate the study at any time. Reasons for discontinuation include but are 
not limited to: 
• Inability to enroll sufficient subjects into the study 
• Good Clinical Practices (GCP) compliance issues that compromise the validity of the study 
Additional information about stopping the study can be found in Sections 9.1 and 9.2. 
Procedures for withdrawal of individual subjects can be found in Section 5.4. 
5.0 
SELECTION OF SUBJECTS 
The study population will include men and women with untreated low-grade B-cell lymphoma 
with at least 2 measurable sites of disease, 1 of which must be palpable and accessible in a low-
risk site (eg, inguinal, axillary, cervical, subcutaneous) for intratumoral injection (denoted as 
“Lesion A” in Treatment Cycle 1) and a second lesion that will not be included in the radiation 
field of the treated lesion. Subjects must not be in immediate need of systemic therapy and must 
be good candidates for “watch and wait”. In addition, subjects must meet the Inclusion and 
Exclusion Criteria as described in detail in Sections 5.1 and 5.2. 
A number of measures will be taken to ensure the safety of subjects participating in this trial. 
These measures will be addressed through inclusion/exclusion criteria and routine monitoring. 
Many of the exclusion criteria for this study were selected to guard the safety of subjects in this 
trial. 


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5.1 
Inclusion Criteria 
A subject must meet all of the following criteria to be eligible for the study: 
1) Biopsy confirmed, untreated low-grade B-cell lymphoma, including follicular (Grade 1, 2, or 
3A) (Harris, Swerdlow et al. 2008), or marginal, or CLL/SLL with lymph node involvement 
2) At least 2 sites of measurable disease per Cheson criteria (must measure at least 1.5 cm in 
any diameter or 1.0 cm in the shortest diameter if one of the diameters is not ≥ 1.5 cm), 1 of 
which must be palpable and easily accessible in a low-risk site (eg, inguinal, axillary, 
cervical, subcutaneous) for intratumoral injection (denoted as “Lesion A” in Treatment Cycle 
1) and at least one additional untreated lesion that is located outside the radiation field of the 
treated lesion (Lesion A) and is accessible for an FNA aspirate. 
3) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 
(Appendix 5) 
4) Aged 18 years and older 
5) Absolute neutrophil count (ANC) ≥ 1500/mm3 
6) Platelet count >100,000/µL 
7) Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) 
8) Serum total bilirubin ≤ 1.5 × the ULN 
9) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN 
10) International normalized ratio or prothrombin time (PT) ≤ 1.5 × ULN unless subject is 
receiving anticoagulant therapy, and the PT or partial thromboplastin time (PTT) must be 
within the therapeutic range of the intended use of anticoagulants 
11) Activated PTT (aPTT) ≤ 1.5 × ULN unless subject is receiving anticoagulant therapy, and the 
PT or PTT is within therapeutic range of intended use of anticoagulants 
12) Female subjects must have a negative urine or serum pregnancy test within 72 hours prior to 
taking study medication if of childbearing potential as defined in this protocol. Women of 
childbearing potential (WOCBP) must be willing to use 2 medically acceptable methods of 
contraception from Day 1 through 120 days after the last dose of trial treatment. The 2 
medically acceptable birth control methods can be either 2 barrier methods or a barrier 
method plus a hormonal method to prevent pregnancy. The following are considered 
adequate barrier methods of contraception:  diaphragm, condom (by the partner), copper 
intrauterine device, sponge, or spermicide as per local regulations or guidelines. Appropriate 
hormonal contraceptives will include any registered and marketed contraceptive agent that 
contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, 
or intramuscular agents). 
13) Ability to understand and sign informed consent form (ICF) and comply with treatment 
protocol 


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5.2 
Exclusion Criteria 
A subject with any one of the following criteria is not eligible for the study: 
1) Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of 
immunosuppressive therapy (including immune modulators or systemic corticosteroids) 
within 7 days prior to study enrollment 
2) Positive for hepatitis B (HBsAg reactive), HCV ribonucleic acid (RNA) qualitative, or 
human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 
3) Diagnosis of mantle or diffuse large-cell lymphoma, Grade 3B follicular lymphoma (Harris, 
Swerdlow et al. 2008), or gastric mucosa-associated lymphoid tissue (MALT) lymphoma 
4) Clinically significant pleural effusion 
5) Active infection including cytomegalovirus 
6) Pregnant or breast feeding within the projected duration of trial participation through 4 
months after the last dose of study treatment 
7) Autoimmune disease including systemic lupus erythematosus, rheumatoid arthritis, multiple 
sclerosis, Sjӧgren’s syndrome, autoimmune thrombocytopenia, history of uveitis, or other if 
clinically significant 
8) Lymphoma involvement of the central nervous system  
9) Received any prior therapy for lymphoma 
10) Use of any investigational agent within the last 28 days 
11) Serious, non-healing wound, ulcer, or bone fracture 
12) If a subject received major surgery, must have recovered adequately from the toxicity and/or 
complications from the intervention prior to enrollment 
13) Clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial 
infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater 
congestive heart failure, serious cardiac arrhythmia requiring medication within 1 year prior 
to Day -1 (Visit 1); Grade II or greater peripheral vascular disease at study entry 
14) Any other significant medical or psychiatric condition, laboratory abnormality, or difficulty 
complying with protocol requirements that may increase the risk associated with study 
participation or study drug administration that may interfere with the interpretation of study 
results and, in the judgment of the investigator, would make the subject inappropriate for this 
study 
15) History of sensitivity to any component of SD-101 


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Protocol DV3-LYM-01 
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CONFIDENTIAL AND PROPRIETARY 
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16) A diagnosis of cancer within the last 3 years prior to enrollment or any known additional 
malignancy that is progressing or requires active treatment. Exceptions are B-cell lymphoma, 
basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone 
potentially curative therapy, and in situ cervical cancer. 
17) Is taking systemic corticosteroids (more than 3 consecutive days) or other 
immunomodulators or immune suppressive medication 
5.3 
Definition of Women of Childbearing Potential 
WOCBP includes any female who has experienced menarche and who has not undergone 
successful surgical sterilization (eg, bilateral tubal ligation, or bilateral oophorectomy) or is not 
postmenopausal. All female subjects are considered to be WOCBP except if they have had a 
hysterectomy, been postmenopausal for at least 2 years or surgically sterile for at least 1 year. 
The only exception is that women who have undergone a hysterectomy are considered not to be 
WOCBP after surgery and are not required to be surgically sterile for a year for study 
eligibility/treatment. 
Postmenopause is defined as: 
• Women on hormone replacement therapy 
• Amenorrhea ≥ 12 consecutive months without another cause and a documented serum 
follicle stimulating hormone (FSH) level >35 mIU/mL 
• Women with irregular menstrual periods and a documented FSH level > 35 mIU/mL 
NOTE:  FSH level testing is not required for women > 62 years old with amenorrhea 
for > 1 year. Women who are using oral contraceptives, other hormonal contraceptives (vaginal 
products, skin patches, or implanted or injectable products), or mechanical products such as an 
intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, 
or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered 
to be of childbearing potential. 
5.4 
Removal of Subjects From Study 
Subjects may choose to withdraw from the study at any time. The reason for withdrawal will be 
recorded on the case report form (CRF). Subjects who do not complete at least 4 injections for 
reasons other than discontinuation for toxicity or who do not have at least one post Screening 
assessment of tumor response may be replaced. Subjects who permanently discontinue study 
treatment prior to completion of all 5 planned doses of SD-101 must be followed per protocol 
according to the Schedule of Assessments for 28 days after the last SD-101 injection (including 
an early discontinuation [ED] Visit) and do not require any further study procedures. At the 
discretion of the investigator, these subjects may continue to be followed with SOC imaging and 
procedures up to a maximum time on study of 720 days (Visit 13) outlined in Appendix 2. 


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Protocol DV3-LYM-01 
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CONFIDENTIAL AND PROPRIETARY 
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Subjects may also be discontinued from the study by the investigator for any of the following 
reasons: 
• Did not receive the first injection of SD-101 
• Is required to permanently discontinue SD-101 injections due to AEs or dose delay due to 
AEs > 14 days as described in Section 9.2 
• Initiation of new treatment for lymphoma 
• Noncompliance with study procedures as determined by the investigator or sponsor 
• At the discretion of the investigator if it is felt to no longer be in the best interest of the 
subject to remain on study 
• The sponsor decides to terminate the study 
The investigator or designee should discuss and consult with Dynavax prior to withdrawing a 
subject from the study before Day 720 (Visit 13). When a subject discontinues prior to study 
completion, the procedures detailed for the ED Visit should be performed. When a subject 
discontinues study prior to completion of all 5 planned SD-101 study treatments, they should 
undergo an ED Visit at 28 days after the last dose of study drug, if possible.  
Additional information about stopping treatment or terminating the study may be found in 
Sections 4.8, 9.1, and 9.2. 
6.0 
STUDY MATERIALS AND SUPPLIES 
6.1 
Low-dose Radiation Therapy 
XRT will be administered locally in 2 fractions of 2 Gy over 2 days (Day -1 [Visit 1] and Day 1 
[Visit 2]) for a total of 4 Gy prior to the first injection of SD-101 (which begins on Study Day 1 
after the XRT is completed). For subjects who have consented to undergo a retreatment of 
SD-101, a second cycle of localized low-dose XRT will be administered over Day 180 [Visit 10] 
and Day 181 [Visit 11] prior to the first SD-101 injection during the retreatment period. 
6.2 
SD-101 
6.2.1 
Investigational Medicinal Product 
SD-101 Drug Product is a clear to slightly opalescent, colorless to pale yellow solution free of 
visible particles and will be supplied by Dynavax in single use vials. Dilution with sterile 0.9%, 
preservative free sodium chloride to the appropriate concentration for dosing will be required for 
all doses; instructions for dilution are provided in the Pharmacy Manual. 
6.2.2 
Instructions for Administration 
SD-101 Drug Product will be administered by intratumoral injection into a single target lesion 
weekly for 5 injections. The doses to be administered are 1 mg, 2 mg, 4 mg, and 8 mg in Part 1 


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Protocol DV3-LYM-01 
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(Dose Escalation). In Part 2 (Expansion), the doses to be administered are 1 mg and 8 mg. In 
addition, subjects in Part 2 will have the option to undergo a second cycle of localized low-dose 
radiation and SD-101 treatment (Cycle 2) at the last dose level that they received in Part 2 Cycle 
1, once they meet eligibility as described in Section 10.3. For all subjects, dose delay for up to 2 
weeks (14 days) is allowed for AEs as described in Section 9.2. For subjects in the 8 mg dose 
cohort, a maximum of 2 dose reductions is allowed (from 8 mg to 6 mg and then to 4 mg, 
respectively) for AEs assessed as possibly related or probably related to SD-101 by the 
investigator (definitions provided in Section 11.3). If the sponsor chooses to close enrollment in 
the 8 mg dose cohort and enroll at a lower intermediate dose cohort, then allowed dose reduction 
levels will be provided by the Dynavax Medical Monitor. No dose reduction is allowed for 
subjects enrolled in the 1 mg cohort. Note:  Dose reductions at the 8 mg dose cohort in Part 2 
require the approval of the Dynavax Medical Monitor by phone or e-mail prior to 
implementing. 
The target lesion, “Lesion A”, will be the tumor site selected to receive XRT and SD-101 
injections in Treatment Cycle 1. The investigator shall endeavor to choose the largest and most 
easily accessible tumor site as Lesion A. Lesion A must be easily palpable and in a low-risk site 
(eg, inguinal, axillary, cervical, subcutaneous). For subjects undergoing retreatment at Day 180, 
the investigator should follow the same guidance as used to select Lesion A for Treatment Cycle 
1. The preference is to select the same treated lesion for Treatment Cycle 2, unless it has 
completely regressed, then the investigator should choose a different lesion to inject for 
Treatment Cycle 2. The same lesion should be injected for a given cycle. The same lesion that is 
irradiated for a given treatment cycle should also be injected. SD-101 injection for a given 
treatment cycle should not be initiated until the subject has received the planned 2 days of XRT 
for that cycle. 
Ultrasound may be used to assess and provide guidance for injection into the injected lesion. 
Notation in the source documents should specify location and size (in 2 dimensions) in as much 
detail as possible. 
Designated study-site personnel will be responsible for preparing and administering the study 
injection. At minimum, syringes will be labeled with the protocol number, subject initials, and 
subject number. 
Prior to injection, the tumor site should be thoroughly cleansed and then wiped with alcohol. 
Ultrasound may be used to assist injection. Injection should be made as close to the center of the 
tumor as possible. All of the drug should be injected. If in subsequent injections, the tumor has 
disappeared, the injection should be made in the same area of the tumor using a subcutaneous 
injection. Details are provided in the Pharmacy Manual. 


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Protocol DV3-LYM-01 
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6.2.3 
Labeling 
At a minimum, SD-101 Drug Product will be labeled with the following information:  product 
name, contents, volume, concentration, sponsor name, and a statement indicating that the drug is 
for investigational use only.  
6.2.4 
Storage and Handling Instructions 
SD-101 Drug Product contains no preservatives and must be stored under refrigerated conditions 
(2°C to 8°C). SD-101 Drug Product is not to be frozen. Vials of SD-101 Drug Product are for 
single use only. 
A detailed description of the storage and handling instructions for SD-101 Drug Product is 
provided in the Pharmacy Manual. 
The clinical supplies storage area at the site must be monitored closely by the designated site 
staff for temperature consistency and documentation of temperature monitoring should be 
maintained. Temperature excursions outside of the recommended storage range may impact 
product quality and must be reported to Dynavax or designee per the detailed instructions in the 
Pharmacy Manual. 
6.2.5 
Control and Accountability of Investigational Medicinal Product 
SD-101, the investigational medicinal product (IMP), must be received by a trained designated 
person at the study site, handled and stored safely and properly, and kept in a secured location 
with limited access. 
The investigator (or responsible designee) must maintain current and accurate records of the 
receipt (documentation from shipments of IMP received), administration (subject-by-subject and 
overall accounting), and return of IMP to a Dynavax-specified facility for destruction. All IMP 
must be stored in a secure location under appropriate conditions with access restricted to 
authorized personnel. 
A study monitor will be responsible for monitoring the drug accountability at the site. The 
monitor should be contacted with any questions concerning administration of IMP. 
Records of IMP accountability, storage, and handling must be made available to the study 
monitor for the purposes of IMP accountability. Any discrepancy and/or deficiency must be 
recorded with an explanation. 
The investigator must retain all used vials and expired, damaged, and unused IMP until 
accountability has been confirmed by the study monitor. Any exceptions to this policy must be 
specifically granted by Dynavax. 


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Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 37 of 84 
At the end of the study, or upon request by Dynavax, all unused IMP must be returned to a 
Dynavax specified facility for adequate disposition. 
Refer to the Pharmacy Manual for detailed instructions on IMP accountability, storage, handling, 
and return. 
IMP may not be used for any purpose other than that described in the protocol. 
6.2.6 
Treatment Compliance 
All study injections and XRT will be administered by designated study personnel only. 
7.0 
TREATMENT OF SUBJECTS 
7.1 
Treatment Administered 
Each subject in Part 1 will receive localized low-dose XRT administered in 2 fractions of 2 Gy 
each for a total of 4 Gy over 2 days (Day-1 [Visit 1], Day 1 [Visit 2]) prior to and followed by 
5 weekly intratumoral SD-101 injections to a single target lesion, Lesion A (same tumor site 
treated throughout the study). 
The dosing schedule will be the same as Part 1 for Part 2 Treatment Cycle 1. In addition, subjects 
in Part 2 will have the option to undergo a second cycle of localized low-dose XRT over Day 
180 [Visit 10] and Day 181 [Visit 11] followed by 5 weekly intratumoral SD-101 injections 
(Treatment Cycle 2). 
By default, the same lesion (Lesion A) treated in Treatment Cycle 1 should be retreated in 
Treatment Cycle 2. If at any point during treatment the treated Lesion A has completely 
regressed, remaining injections will be given by subcutaneous injection into the site of the 
treated Lesion A. Retreatment at Day 180 (Treatment Cycle 2) may only be applied to a lesion 
other than Lesion A if Lesion A has regressed and does not meet minimum size requirement as 
described in the retreatment criteria unless otherwise approved by a Dynavax Medical Monitor. 
Once a lesion is selected, the same lesion must be injected for a given treatment cycle. 
The SD-101 doses planned for administration in the Part 1 dose escalation are 1 mg, 2 mg, 4 mg, 
and 8 mg. Subjects enrolled in Part 1 will be assigned to the current dose being evaluated, and 
subjects enrolled in Part 2 will be assigned to the 1 mg or 8 mg dose cohorts in the order of 
subject enrollment and a dose level which is open and available at the time of enrollment. 
Subjects who have consented to Cycle 2 treatment will receive SD-101 at the last dose level they 
received for Part 2 Cycle 1. Intra-subject dose escalation is not permitted. Dose reduction for 
AEs are only allowed for the 8 mg cohort in Part 2 or other lower dose Part 2 cohort per the 
Dynavax Medical Monitor. No dose reductions for AEs are allowed for the 1 mg cohort in Part 2 
or any Part 1 subjects. For Part 2, dose interruptions (allowed for all subjects) may occur 
(Section 6.2.2) and rules for dose reductions (not allowed for subjects in the 1 mg dose cohort) 
are given in Section 9.0. 


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7.2 
Treatment Period 
The treatment period is 30 days for each cycle. For Treatment Cycle 1, localized low-dose XRT 
will be administered on Day-1 (Visit 1) and Day 1 (Visit 2) prior to the first SD-101 injection. 
SD-101 injections are to be administered at Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 5), 
Day 22 (Visit 6), and Day 29 (Visit 7). For the optional Treatment Cycle 2, localized low-dose 
XRT will be administered on Day 180 (Visit 10) and Day 181 (Visit 11) prior to the first SD-101 
injection during the retreatment period. SD-101 injections are to be administered at Day 181 
(Visit 11), Day 188 (Visit 12), Day 195 (Visit 14), Day 202 (Visit 15), and Day 209 (Visit 16). 
Subjects will be followed until TTNT or until approximately 2 years after the first injection of 
SD-101 (Day 720 [Visit 13 for single-cycle treatment and Visit 21 for retreatment]), whichever 
occurs earlier. 
7.3 
Treatment Precaution 
IFN-alpha has been shown to inhibit cytochrome P450 (CYP) enzyme 1A2 (Brennan 2012). 
Since SD-101induces IFN-alpha, SD-101 may inhibit metabolism of drugs by CYP 1A2. The 
following drugs should be used with caution from Day 1 through Day 36 (and optional Day 180 
through Day 216 if consent is provided for SD-101 retreatment):  caffeine, theophylline, 
warfarin, tricyclic antidepressants, clozapine, fluvoxamine, ciprofloxacin, propranolol, and 
verapamil. 
7.4 
Prohibited Treatments or Therapies 
Subjects may receive other medications that the investigator deems to be medically necessary, 
with the exception of the medications listed below, which are prohibited during the trial. Subjects 
who, in the assessment by the investigator, require the use of any of the following treatments for 
clinical management should be removed from study treatment (see Section 5.4): 
• Antineoplastic systemic chemotherapy or biologic therapy 
• Any investigational therapy 
• Immunosuppressive agents not specified in this protocol (except when used for treating 
AEs). If used for AEs, the agents must be discontinued prior to resumption of SD-101. 
• Systemic steroids and topical steroids whose absorption is expected to result in systemically 
immunosuppressive steroid levels (that exceeds 10 mg per day of prednisone or equivalent) 
is prohibited during study treatment and until 30 days after the last dose of SD-101 and is 
only allowed when used for the acute treatment of AEs. 
• Additional XRT after the initiation of SD-101 with the exception that XRT to a symptomatic 
solitary lesion or to the brain may be considered on an individual case by case basis with 
Dynavax Medical Monitor approval 


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• Prophylactic use of colony-stimulating factors including granulocyte colony-stimulating 
factor (G-CSF), pegylated G-CSF, or granulocyte macrophage colony-stimulating factor 
(GM-CSF) 
• Surgery, unless approved by the Dynavax Medical Monitor 
7.5 
Permitted Therapy 
Topical or inhaled or intranasal corticosteroids (with minimal systemic absorption) and 
non-absorbed intra-articular steroid injections are permitted to treat AEs and may be continued 
with approval of the Dynavax Medical Monitor. A brief (< 24 hours) course of steroids for 
prophylaxis against contrast dye allergy is permitted for subjects undergoing tumor assessments 
per institutional standard. 
For flu-like symptoms, prophylactic treatment is recommended pre and post-treatment for the 8 
mg cohort and is recommended pre- and post-SD-101 dosing for all subsequent dosing for 1 mg 
cohort subjects who experience post-treatment flu-like symptoms. 
For All Subjects in the 8 mg Dose cohort Pre-Treatment Prophylaxis: 
• Subjects should be treated prophylactically with 1 gm acetaminophen approximately 
2 hours before and 4 to 6 hours after injection with SD-101. 
• Subjects should continue dosing with acetaminophen for 48 hours per acetaminophen 
dosing guidelines (not to exceed a dose of 3 gm in 24 hours). 
• Ibuprofen may also be given pre- and post-treatment for prophylaxis and is 
recommended for subsequent dosing if subjects have flu-like symptoms that are not 
adequately treated by acetaminophen. 
For All Part 2 Subjects in the 1 mg Dose cohort Pre-Treatment Prophylaxis: 
• Subjects are required to be treated prophylactically at the 1 mg dose with 1 gm 
acetaminophen approximately 2 hours before each injection of SD-101. 
• If a subject has significant flu-like symptoms at any dose level, then follow the pre-
treatment prophylaxis listed for the 8 mg cohort above. 
For All Subjects Post-Treatment in Part 2: 
• If a subject experiences any flu-like symptoms up to 48 hours following SD-101 
injection, then the subject may take acetaminophen (maximum 3 gm per day), 
odansetron, or prochlorperazine as needed for 24 to 48 hours post-injection. If 
symptoms are severe and unresponsive to standard therapy, codeine may be used. 
If the flu-like symptoms that are not adequately treated with acetaminophen, ibuprofen may also 
be used pre- and/or post treatment. Efforts should be made to keep all other concurrent 


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medications at stable doses during the trial and to refrain from starting any new medications, 
unless clinically indicated. Therapy to prevent or treat local and/or systemic reactions following 
administration of study drug may include analgesics, antipyretics, and antihistamines. 
8.0 
ASSESSMENT OF RESPONSE 
Response assessments will be performed at specified time points as listed in the Schedule of 
Study Assessments (Appendix 1 and Appendix 2). Disease response (radiographic and biomarker 
[FNA] samples) will be assessed for treated and untreated disease. Treated disease is the injected 
and irradiated lesion (denoted as “Lesion A” in Cycle 1) and untreated disease is all other target 
lesions identified at Screening (up to 5 lesions; denoted as “Lesion B through F” in Cycle 1). All 
untreated disease that is used for assessment of response and recorded in the eCRF must be 
located outside the radiation field of the treated lesion (Lesion A). 
8.1 
Interferon-inducible Genes 
IFN-inducible gene expression will be measured to determine the induction of IFN-alpha by 
different doses of SD-101. The levels of IFN-inducible gene expression, along with all available 
data, will be used to determine the Optimal Dose of SD-101 for Part 2. 
8.2 
RNA Analysis  
Blood for RNA analysis to explore changes in gene expression in response to treatment will be 
collected.  
8.3 
Biomarker Analysis 
When collected, FNA samples of the treated lesion (denoted as “Lesion A” in Cycle 1), and 1 or 
more other accessible untreated lesions which are located outside the radiation field of the treated 
lesion (denoted as “Lesions B through F” in Cycle 1), will be analyzed for changes in correlative 
biomarkers (changes over time relative to baseline). In Part 2, this biopsy requirement will 
include 2 FNA samples collected at each required timepoint for biomarker analysis of both FNA 
samples for cellular phenotyping and NanoString RNA gene expression analysis. For subjects 
who undergo a second cycle of localized low-dose XRT and SD-101 injections starting at Day 
180 in Part 2, they will have additional tumor biopsies collected at Day 180 (Visit 10), Day 188 
(Visit 12), and Day 216 (Visit 17) from the treated lesion. A biopsy from an untreated lesion 
selected outside the field of radiation of the treated lesion may be collected at Day 180 (Visit 10), 
Day 216 (Visit 17), and Day 270 (Visit 18) as outlined in Section 10.9 and Appendix 3. The 
biopsies obtained following treatment Cycle 2 are only to be obtained for subjects undergoing 
Cycle 2 retreatment and only requires a single FNA of each lesion biopsied at a given timepoint. 
The biomarker analysis will only include NanoString RNA gene expression analysis (not cellular 
phenotyping). Note:  If an untreated lesion is not available or accessible, an FNA sample 
collection of an untreated lesion is not required for Cycle 2.


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8.4 
Response Evaluation and Criteria 
Response to treatment will be evaluated by the investigator at 3 and 6 months (and 9 months for 
subjects who undergo Cycle 2 treatment [Day 180]) after the first study injection and then every 
6 months for the remainder of the trial. 
Response of lesions will be assessed by CT or CT/PET and bone marrow biopsy using the 
Cheson criteria for lymphomas (Cheson, Horning et al. 1999). Response will be assessed on the 
basis of clinical, radiologic, and pathologic (ie, bone marrow) criteria: 
1) At a minimum, thoracic, abdominal, and pelvic CT scans will be performed even if those 
areas were not initially involved because of the unpredictable pattern of recurrence in NHL. 
CT/PET may be used if they are the standard tools for assessing disease status at a 
participating institution. 
2) Unilateral bone marrow biopsy and aspirates will be performed at Screening if not previously 
performed or if performed more than 90 days previously with negative results. The bone 
marrow biopsy will be performed to confirm a complete response (CR) if the subject was 
initially positive or if it is clinically indicated by new abnormalities in the peripheral blood 
counts or blood smear. 
Response of lesions will be recorded on the CRF based on the definitions in Table 8-1 or 
Appendix 4 as appropriate. Suspected relapse or disease progression must be confirmed by 
physical exam, laboratory assessments, repeat bone marrow biopsy (Cheson, Horning et al. 
1999) and CT scan. If confirmed, progressive disease should be reported to the sponsor within 7 
days. Subjects with suspected relapse or disease progression should continue to follow study 
procedures until they need another therapy. If a subject requires another therapy, date of 
treatment and type of treatment will be recorded and they will then be removed from the trial. 
Tumor progression is defined as ≥ 50% increase from nadir in the sum of the products of the 
greatest diameters (SPD), as defined in the Cheson response criteria for NHL (Cheson, Horning 
et al. 1999) (Table 8-1). The response criteria per Cheson (1999) should be recorded in the 
database. However, if the subject is evaluated by CT/PET scan then tumor response criteria 
should be evaluated using updated Cheson criteria (Cheson, Pfistner et al. 2007), which includes 
CT and PET scans.


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Table 8-1: 
Response Criteria for Non-Hodgkin’s Lymphoma 
Response 
Category 
Physical 
Examination 
Lymph Nodes 
Lymph Node Masses 
Bone Marrow 
Complete 
Response 
Normal 
Normal 
Normal 
Normal 
Complete 
Response/ 
Unconfirmed 
Normal 
Normal 
Normal 
Indeterminate 
 
Normal 
Normal 
≥ 75% decrease 
Normal or indeterminate 
Partial 
Response 
Normal 
Normal 
Normal 
Positive 
 
Normal 
≥ 50% decrease 
≥ 50% decrease 
Irrelevant 
 
Decrease in 
liver/spleen 
≥ 50% decrease 
≥ 50% decrease 
Irrelevant 
Relapse/ 
Progression 
Enlarging liver/ 
spleen; new sites 
New or increased 
New or increased 
Reappearance 
Source:  (Cheson, Horning et al. 1999). Stable disease is defined as less than a partial response but is not progressive disease. 
9.0 
MANAGEMENT OF STUDY TREATMENT TOXICITIES 
During the study follow-up period, safety will be evaluated through the careful monitoring of all 
clinical and laboratory AEs. Safety assessments will include specified laboratory parameters (eg, 
complete blood count [CBC], serum chemistry). See Section 10.4.5 for additional details of 
laboratory testing. 
9.1 
Dose-limiting Toxicity and Stopping Rules 
Standard safety monitoring consistent with International Conference on Harmonisation (ICH) 
guidelines will be employed for DLT assessment and dose-escalation decisions during the Part 1 
(Dose Escalation) of the study. All AEs will be considered in DLT assessment unless an event is 
clearly unrelated to SD-101. Before dose escalation at each dose level and at any other time that 
safety data warrant review during Cycle 1 or Cycle 2, as applicable, the coordinating principal 
investigator will participate in a teleconference with the Dynavax Medical Monitor and Contract 
Research Organization (CRO) Medical Monitor to review all safety data.  
All AEs, including DLTs, are to be reported according to instructions in the Study Reference 
Manual and graded using the National Cancer Institute CTCAE, Version 4.03 (National Cancer 
Institute 2010). If a subject experiences a DLT, he or she will be treated according to clinical 
practice and will be monitored for resolution of the toxicity. For dose escalation purposes, a DLT 
will be defined as any of the following AEs occurring from the time of the first injection (Day 
1 [Visit 2]) through 7 days following the last injection (Day 36 [Visit 8]): 
• Any non-hematological toxicity ≥ Grade 3 except for alopecia or nausea uncontrolled by 
medical management 


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• Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any requirement 
for platelet transfusion 
• Febrile neutropenia of any duration (ANC < 1000/mm3, temperature ≥ 38.5°C) 
• Grade 4 neutropenia lasting more than 5 days 
• Grade 4 anemia, unexplained by underlying disease 
• Any Grade ≥ 2 toxicity related to SD-101 (eg, post-injection reaction or influenza-like 
illness) that does not resolve to Grade ≤ 1 with standard treatment by the time of the next 
treatment 
If a subject has a DLT they should not receive further injections and should be encouraged to 
complete trial participation and followed for safety through Day 720 (Visit 13). 
If a subject is prevented from receiving additional injections per Section 9.2, a review of related 
safety information will be completed by the Dynavax Medical Monitor, or designee, to 
determine if the subject should continue in the study. 
The protocol may be discontinued by the sponsor at any time (Section 4.8). In the absence of 
unacceptable treatment-related toxicity or disease progression, subjects may be considered to 
receive SD-101 treatment for up to 1 year at the discretion of the investigator and beyond 1 year 
with the agreement of the investigator and the sponsor, under a compassionate use protocol.  
9.2 
Dose Modification for Adverse Events  
Withhold SD-101 for any of the following that are assessed as possibly related or probably 
related to SD-101 as defined in Section 11.5. 
• Grade 3 drug-related AEs of any duration or Grade 3 injection-site reaction (that persists for 
greater than 7 days). SD-101 treatment may be resumed once the AE has resolved to Grade 1 
or baseline with standard treatment. Subjects in the 8 mg cohort may undergo up to 2 dose 
reductions per investigator decision and Dynavax Medical Monitor approval as described in 
Section 9.2. If SD-101 is held for Grade 3 neutropenia, the neutrophil count must recover to 
≥ 1500 cells/mm3 prior to resuming SD-101 treatment. 
• If a subject requires > 10 mg per day of prednisone or equivalent to treat an AE, SD-101 may 
be resumed when the corticosteroid is discontinued or the dose is decreased to ≤ 10 mg per 
day of prednisone (or equivalent). 
A minimum of 5 days must also elapse between injections. If the 5-day interval cannot be 
adhered to, then the next injection should be delayed and administered at the time of the next 
scheduled injection. If SD-101 is delayed for > 14 days due to an AE, then SD-101 should not be 
resumed.


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Withdraw SD-101 for any of the following that are assessed as possibly related or probably 
related to SD-101 as defined in Section 11.5: 
• Grade 3 AE (except for alopecia or nausea) which is not controlled by medical management 
• Grade 4 AE 
• SD-101 dosing is delayed for more than 14 days 
• SAE that is assessed as a suspected adverse reaction (SAR) (Section 11.3.2) or an adverse 
reaction (Section 11.3.1) 
9.3 
Reasons for Stopping a Subject From Receiving Additional Injections 
Subjects may be discontinued from study treatment by the investigator for any of the following 
reasons: 
• Noncompliance with study procedures as determined by the investigator or sponsor 
• Pregnancy or begins breastfeeding 
• Use of or need for prohibited medications 
• Intercurrent illness that prevents further administration of treatment 
• Unacceptable AEs as defined in Section 9.2 
• Adverse drug reaction that requires study drug discontinuation per protocol (see Section 9.2) 
• Need for > 2 dose delays due to toxicity as per the dose modification guidelines described in 
Section 9.2 
If in the opinion of the investigator, a change or discontinuation of therapy would be in the best 
interest of the subject. 
The investigator or designee must notify Dynavax when a subject has been discontinued from 
treatment. Any subject who is discontinued from treatment prior to the completion of planned 5 
doses of SD-101 should be followed up with an ED visit scheduled 28 days after the last dose of 
SD-101. The subject then should be permanently discontinued from the study or may continue to 
be followed on study with SOC laboratory, x-ray, and safety evaluation until Day 720 (Visit 13). 
9.4 
Management of Subject Safety 
During active treatment, subjects undergo targeted physical exams and laboratory assessments, 
which will include a CBC with differential, coagulation testing, platelet assessment, chemistry, 
liver function tests, and LDH. 
Subjects who have consented to receive a second cycle of study treatment will have to meet 
eligibility as described in Section 10.3. 


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Subjects should receive full supportive care to treat injection site reactions and other toxicities. 
Management of adverse effects will be at the discretion of the treating investigator. An 
unscheduled visit (Section 10.10) should be performed if there is suspected disease progression 
or subject safety concerns. All supportive therapies will be recorded in the subject’s CRF. 
Injection-site reactions are expected to spontaneously subside. Local reactions are to be treated at 
the discretion of the treating physician. The site is not to be injected if local pain, tenderness, or 
swelling persists from a previous injection or other cause; the injection may be postponed until 
the symptoms have resolved or the injection may be skipped, following discussion with the 
Medical Monitor. 
Subjects who are stopped from receiving additional study injections will be followed for safety 
through Day 720 (Visit 13). 
Please refer to Section 10.11 for procedures regarding ED. 
9.5 
Pre-Treatment Prophylaxis and Post-Treatment 
Based on the safety review of these AEs in Part 1, prophylaxis and treatment of SD-101 related 
flu-like symptoms are recommended. Details are provided in Section 7.5. 
10.0 
TRIAL ASSESSMENTS 
All tests and evaluations required at specified time points are listed in the Schedule of Study 
Assessments (Appendix 1, Appendix 2, and Appendix 3). The results of these tests and 
evaluations must be entered in the subject’s source document and also recorded on the subject's 
electronic data capture (EDC) CRF. Additional evaluations may be done at the discretion of the 
investigator and with sponsor approval. 
Procedures to be performed for each study visit are described in Appendix 1, Appendix 2, and 
Appendix 3. 
For subjects who have not consented to receive Cycle 2 treatment of localized low-dose XRT 
and SD-101, these subjects will continue on study at Day 180 (Visit 10) and complete follow-up 
procedures as outlined in Appendix 2. These subjects include all Part 1 and Part 2 subjects who 
do not qualify for SD-101 retreatment as outlined in Section 10.3 or have withdrawn consent 
prior to receiving additional SD-101 injections in this study. 
10.1 
Informed Consent and Screening Log 
The investigator or designee must review the ICF with each prospective subject to be certain that 
the prospective subject understands the procedures and risks of the trial. Prospective subjects 
who wish to participate in the trial must provide written informed consent by signing the ICF 
before undergoing any Screening procedures (Appendix 1, Appendix 2, and Appendix 3). 
Informed consent must be obtained for subjects who choose to receive retreatment prior to 


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undergoing Cycle 2 treatment of localized low-dose XRT and SD-101 injections. A subject may 
withdraw consent to be treated with SD-101 at any time prior to or during the retreatment period. 
The investigator or designee will maintain a log of all subjects who sign the ICF. At a minimum, 
the log will include a subject identifier, the dates of informed consent and screening procedures, 
the outcome of the screening, and the reason the subject did not enroll in the trial. 
Additional requirements for informed consent are presented in Section 15.3. 
10.2 
Screening Assessments 
Assessments to be completed during the Screening period are listed in Appendix 1, Appendix 2, 
and Appendix 3. 
If a subject has results from SOC visits for any of the following assessments completed within 30 
days prior to signing the ICF for this trial, those results may be used in lieu of repeating the study 
procedures during the 28-day Screening period: 
• Vital signs 
• Physical exam 
• Electrocardiogram (ECG) 
• Hepatitis and HIV testing 
• Chemistry 
• Hematology 
• Coagulation 
Please note that SOC CT or PET/CT imaging conducted prior to the 28-day Screening period 
will not be permitted. This assessment must be completed at Screening to ensure current baseline 
measurements are captured. In addition, add a copy of a record of lesion size at a timepoint at 
least 3 months prior to baseline should be added to the subject’s CRF. 
10.3 
Cycle 2 Treatment 
Subjects in Part 2 must provide consent to receive a second cycle of study treatment (2 days of 
localized low-dose radiation over Day 180 and Day 181 followed by 5 weekly SD-101 injections 
starting on Day 181 at the last dose level that the subjects were previously treated with in Part 2 
Treatment Cycle 1).  
• Understand and consent to receive SD-101 retreatment, including all additional imaging 
and safety laboratory procedures and assessments 
• Have at least stable disease assessed by Cheson criteria for all Cycle 1 untreated lesions 
(excluding Lesion A) on Day 180 imaging 


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• Have at least 1 measurable and accessible lesion on Day 180 imaging which is injectable 
and meets the size criteria as a target lesion per Cheson criteria 
• Have an absolute neutrophil count (ANC) ≥ 1500/mm3 and platelet count >100,000/µL 
• Female subjects must have a negative urine or serum pregnancy test within 72 hours prior 
to taking study medication if of childbearing potential as defined in this protocol. 
WOCBP (Section 5.3) must be willing to use 2 medically acceptable methods of 
contraception from Day 1 through 120 days after the last dose of Cycle 2 treatment. 
Pregnant or breastfeeding subjects are not eligible to receive further study treatment. 
Subjects are INELIGIBLE to receive a second cycle of study treatment if one or more criteria 
are met below: 
• Prior DLT on this study during Treatment Cycle 1 
• History of sensitivity to any component of SD-101 
10.4 
Safety Assessments 
The safety assessments listed below will be the same for Part 1 and Part 2. The Schedule of 
Study Assessments is provided in Appendix 1, Appendix 2, and Appendix 3. 
10.4.1 
Medical and Medication History 
Medical history includes clinically significant diseases, surgeries, cancer history, and all 
medications (eg, prescription drugs, over-the-counter drugs, herbal/homeopathic remedies, 
nutritional supplements) used by the subject within 28 days prior to the Screening visit 
(Appendix 1, Appendix 2, and Appendix 3). 
10.4.2 
Vital Signs 
Vital signs will be recorded and will include measurements of heart rate, respiratory rate, and 
systolic and diastolic blood pressure. Vital signs taken at injection visits will include oral 
temperature. See Appendix 1, Appendix 2, and Appendix 3 for Schedule of Study Assessments. 
10.4.3 
Physical Examinations 
The investigator or qualified designee will conduct physical examinations. A complete physical 
examination will be conducted at Screening and ED visits, and a targeted physical examination 
(based on interval history and/or AEs) will be conducted at all other visits (Appendix 1, 
Appendix 2, and Appendix 3). 
Assessment of the Liver and Spleen must be done during the physical exams that are completed 
at Screening, Day 90, Day 180, Day 360, Day 540, Day 720, Unscheduled Visit, and ED Visit, 
where lesions are evaluated and the Cheson criteria are used to assess overall response. 


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10.4.4 
Electrocardiogram 
An ECG (12-lead with standard parameters of heart rate, shape, size and duration of P wave, P-R 
interval, QRS, and T wave configuration) will be performed at Screening, after treatment on Day 
15 (Visit 5), and on Day 36 (Visit 8) (Appendix 1, Appendix 2, and Appendix 3). 
10.4.5 
Safety Laboratory Assessments 
Laboratory assessments are listed below and will be performed according to the Schedule of 
Study Assessments (Appendix 1, Appendix 2, and Appendix 3). All safety laboratory tests are to 
be performed at the trial site’s local laboratory. Sample collections are to be done pre-injection 
on treatment days. 
• Hepatitis and HIV testing at Screening:  hepatitis B surface antigen, hepatitis B core antigen, 
anti-HCV, and anti-HIV 
• Chemistry:  sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), Cr, 
glucose, calcium, AST, ALT, gamma glutamyl transpeptidase (GGT), LDH, bilirubin, 
alkaline phosphatase, and C-reactive protein (CRP) 
• Hematology:  Hgb, hematocrit, white blood cell count with differential, and platelet count 
• Coagulation:  prothrombin time (PT) and activated partial thromboplastin time (APTT) 
• For WOCBP, serum pregnancy testing will be conducted at Screening. Serum or urine 
pregnancy must be negative prior to initiation of study treatment as outlined in Appendix 1, 
Appendix 2, and Appendix 3. Serum or urine pregnancy must be negative prior to study 
treatment. Dipstick can be used. All female subjects are considered to be WOCBP except as 
defined in Section 5.3. 
• Reserve serum aliquot specimens will be collected and stored frozen for possible future 
testing. 
• Blood for antibodies to double-stranded deoxyribonucleic acid (anti-dsDNA) will be 
collected as outlined in Appendix 1, Appendix 2, and Appendix 3. Quantitative results for 
anti-dsDNA are required. 
• Additional details for specific tests are provided in the Laboratory Manual.


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10.4.6 
Injection-site Reaction Assessments 
Assessments of local injection-site reactions to intratumoral injections will be collected for 
7 days following each injection. 
Prior to study injection on Day 1 (Visit 2), Day 8 (Visit 3), Day 15 (Visit 5), Day 22 (Visit 6), 
and Day 29 (Visit 7), subjects will receive a new Diary Card with instructions to measure and 
record local injection-site reactions and solicited AEs. The completed Diary Cards will be 
reviewed with the subjects at their next study visit. 
Subjects are to be observed for a minimum of 30 minutes post-injection for the collection of any 
local injection-site reactions during the SD-101 Treatment Cycle 1 and optional Treatment 
Cycle 2. 
See Appendix 1, Appendix 2, and Appendix 3 for Schedule of Study Assessments. 
10.4.7 
Adverse Events 
AEs, as defined in Section 11.3, will be evaluated from immediately after the first study 
treatment from Day -1 (Visit 1) through Day 90 (Visit 9) and, if dosing in Cycle 2, from Day 180 
[Visit 10] until Day 270 [Visit 18] (Appendix 1, Appendix 2, and Appendix 3). AE assessments 
at the ED Visit should occur 7 days or more after their last study injection. Subjects who are 
withdrawn due to an AE should have an AE assessment completed 28 days or more after their 
last study drug injection. If the subject is discontinuing study, the ED can be performed at the 
same visit as the AE assessment. 
10.4.8 
Serious Adverse Events 
SAEs, as defined in Section 11.4.1, will be evaluated from the time the consent is signed through 
the duration of trial participation (Appendix 1, Appendix 2, and Appendix 3). Any SAE 
occurring from the time the consent is signed through completion, whether or not related to IMP, 
must be reported within 24 hours to Dynavax or its designee within 24 hours of the knowledge of 
the event. 
10.4.9 
 Concomitant Medications 
Any prescription medication and over-the-counter drug or natural/herbal preparations, including 
vitamins and dietary supplements, including those for the treatment of any AEs, taken by the 
subject from Screening through the end of the treatment period (Day 90 [Visit 9] for 1 cycle of 
treatment or Day 270 [Visit 18] for 2 cycles of treatment) will be reported (Appendix 1, 
Appendix 2, and Appendix 3). Concomitant medications used to treat an SAE or 
immunomodulator drugs taken after Day 90 (Visit 9) for 1 cycle of treatment or after Day 270 
(Visit 18) for 2 cycles of treatment through Day 720 (Visit 13) or ED are also to be reported.


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10.5 
Disease Assessments 
Disease assessments will be the same for Part 1 and Part 2 (Appendix 1, Appendix 2, and 
Appendix 3). 
• Disease assessment will consist of CT scan of neck, chest, abdomen and pelvis, and other 
areas as clinically indicated. PET scans will only be permitted if PET/CT is SOC at the 
participating institution. 
• Unilateral bone marrow biopsy and aspirate will be performed at Screening if not previously 
performed or if performed more than 90 days previously with negative results. The bone 
marrow biopsy will be performed to confirm a CR if they were initially positive or if it is 
clinically indicated by new abnormalities in the peripheral blood counts or blood smear. 
10.6 
Pharmacokinetic Assessments 
PK assessments will be done for Part 1 only. PK samples will be collected for Part 1 before and 
after the second dose of SD-101 in Part 1 only. Collections are to be performed pre-dose; 1, 2, 4, 
and 6 hours (± 10 minutes) post-dose on Day 1; and 24 (± 3) hours post-dose on Day 9 in Part 1 
only (Appendix 1). 
10.7 
Pharmacodynamic Assessments 
Details of testing for PD assessments (blood draws and FNA sampling) are provided in the 
Schedule of Assessments (Appendix 1, Appendix 2, and Appendix 3) and the Laboratory 
Manual. Blood will be collected for RNA analysis. Collections are to be done pre-XRT or 
pre-injection on treatment days. 
• Blood for IFN-alpha inducible gene expression. Collections are to be done pre-XRT or 
pre-injection on treatment days. On Day 9, the sample is to be collected 24 (± 3) hours after 
the Day 8 injection. These IFN samples will also be collected in Part 2 for subjects who have 
consented to receive Cycle 2 treatment of SD-101 injections; on Day 189, the sample is to be 
collected 24 (± 3) hours after the Day 188 injection. 
• Blood for RNA expression assessment is collected in both Part 1 and Part 2 as listed in the 
Schedule of Assessments. Samples will be retained for possible gene expression studies to be 
performed using other techniques. 
• RNA gene expression analysis and profiling will be conducted on one of the 2 FNA samples 
of tumor lesions in Part 2 Treatment Cycle 1 (target treated lesion [denoted as “Lesion A”] 
and an untreated lesion [denoted as “Lesion B”]). In Part 2 Treatment Cycle 2, a single FNA 
sample of the target treated and the untreated lesions will be collected. Note:  If an untreated 
lesion is not available or accessible for subjects at Day 180 who are undergoing Cycle 2, an 
FNA sample collection of an untreated lesion is not required Details are provided in the 
Laboratory Manual. 


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• Assessment of tumor infiltrating lymphocytes will be conducted on the second FNA sample 
of tumor lesions (treated and untreated) in Part 2 Treatment Cycle 1. Note:  If an untreated 
lesion is not available or accessible, an FNA sample collection of an untreated lesion is not 
required. There will be no FNA samples collected in Part 2 Treatment Cycle 2 that will 
involve the analysis of tumor infiltrating lymphocytes with flow cytometry. Details are 
provided in the Laboratory Manual. 
10.8 
Immunogenicity Assessment 
Blood for antibodies to SD-101 will be collected at Days -1 (Visit 1), 36 (Visit 8), and 360 (Visit 
11) in Part 1 and Part 2 (Appendix 1, Appendix 2), and optional Days 181 (Visit 11), 216 (Visit 
17), 270 (Visit 18) and 360 (Visit 19) for SD-101 retreatment in Part 2 (Appendix 3). 
10.9 
Fine Needle Aspirate of Tumor Lesions 
Exploratory assessments for Part 1 and Part 2 are described separately in the Schedule of Study 
Assessments (Appendix 1, Appendix 2, and Appendix 3). 
• In Part 1, a single FNA sampling is obtained from the treated lesion (Lesion A) on Day-1 and 
Day 8 with optional sampling on Day 36 and following disease progression. FNA sampling 
of an additional untreated (Lesion B) is optional but recommended. 
• In Part 2 Treatment Cycle 1, 2 FNA samples each from each lesion biopsied is required. FNA 
sampling is required from both the treated lesion (Lesion A) and a second untreated lesion 
(Lesion B) selected outside the field of radiation of the treated lesion (Lesion A). Two FNA 
samples will be collected each from Lesion A at Day 1, Day 8, and Day 36. Two FNA 
samples will be collected each from Lesion B at Day 1, Day 36, and Day 90. 
• In Part 2 Treatment Cycle 2, one single FNA sample collected from the treated lesion is 
required, and one single FNA sample collected from the untreated lesion that is located 
outside the field of radiation of the treated lesion is recommended. The FNA sample 
collected from the untreated lesion must be selected outside the field of radiation of the 
treated lesion. FNA sampling is required at Day 180, Day 188 and Day 216 from the treated 
lesion. FNA sampling from the untreated lesion is recommended but optional at Day 180, 
Day 216 and Day 270. Note:  If a second untreated lesion is not available or accessible, an 
FNA sample collection of a second untreated lesion is not required. 
10.10 Unscheduled Visit 
An unscheduled visit (Appendix 1, Appendix 2, and Appendix 3) should be performed if there is 
suspected disease progression or subject safety concerns. If disease progression is suspected, it 
must be reported to the sponsor within 24 hours (Section 8.4) and confirmation of disease 
progression should be documented by completing a targeted physical examination (including 
assessment of the Liver and Spleen [Section 10.4.3]) based on subject-reported symptoms 
including vital signs (heart rate, blood pressure, respiratory rate), serum chemistry, hematology, 
CT scan, and unilateral bone marrow biopsy and aspirate if clinically indicated by new 


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abnormalities in the peripheral blood counts or blood smear (Section 8.4). Fine needle aspirate 
samples may be collected at an unscheduled visit, if the ± 21 days visit window at Visit 8 is used, 
or at a visit to assess disease progression. If an unscheduled visit is performed because of a safety 
concern related to IMP, at a minimum, the following should be performed:  a targeted physical 
examination based on subject-reported symptoms including vital signs (heart rate, blood 
pressure, and respiratory rate), serum chemistry, and hematology. 
10.11 Early Discontinuation Visit 
Subjects should be encouraged to complete the entire study; however, if a subject decides to 
withdraw, every effort should be made to complete the ED visit (Appendix 1, Appendix 2, and 
Appendix 3) within a window no later than the next scheduled study visit (and at least 7 days 
following the last injection). Subjects who are withdrawn due to an AE should have an AE 
assessment completed 28 days or more after their last study drug injection. If the subject is 
discontinuing study, the ED can be performed at the same visit as the AE assessment. 
11.0 
 REPORTING AND DOCUMENTATION OF ADVERSE EVENTS 
11.1 
Investigator’s Responsibilities 
This trial will be conducted in accordance with the protocol; GCP as defined in ICH guidelines 
and applicable local legal and regulatory requirements. Investigators are responsible for 
monitoring the safety of subjects throughout the course of the study and for providing 
appropriate medical care. The investigator will perform all tasks directly or is responsible for 
overseeing and training qualified site personnel as delegated to perform trial tasks. In addition, 
investigators are responsible for alerting Dynavax to any event that seems unusual and for 
reporting all AEs, SAEs, and deaths in the appropriate CRFs. 
11.2 
Injection-site Reactions 
Local reactions (eg, redness, swelling, pain at or near the injection site) to intratumoral injections 
will be collected for 7 days following each injection. Local injection site reactions are considered 
AEs if they persist longer than 7 days. The severity for all local reactions (including those which 
persist longer than 7 days) will be graded using the Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Appendix 6). 
Dynavax will capture all local reactions that occur, even if their diameter of the largest 
dimension does not meet a Grade 1 on the severity scale. As such, any reaction smaller than this 
size cannot be graded, but will still be recorded in the clinical database and the severity will be 
marked as “not applicable” (“N/A”). 
The subject will be provided with a Diary Card at timepoints outlined in the Schedule of Study 
Assessments. Instructions will be provided to the subject on measuring and recording local 
injection-site reaction data (eg, redness, swelling, pain at or near injection site). Further, the 
Diary Card solicits certain pre-defined AEs (eg, malaise, headache, chills, myalgia, fatigue, 


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fever) and other health changes. All data documented by the subject on Diary Cards will be 
collected, reviewed by the study nurse/coordinator with the subject, and recorded on the 
appropriate CRF. The severity of predefined AEs and other health changes will be assessed and 
confirmed by the investigator and will be graded using the CTCAE Version 4.03 grading scale 
by system organ class (National Cancer Institute 2010). If the appropriate grading or description 
cannot be applied, then the investigator may elect to use the adapted CTCAE Version 4.03 
grading scale (Table 11-1) to assess the AE. 
Further information will be provided in the Study Reference Manual. 
11.3 
Adverse Events 
An AE is any untoward medical occurrence in a subject who receives a pharmaceutical product, 
whether or not there is a causal relationship with the investigational treatment. An AE can 
therefore be any unfavorable and unintended sign (including a clinically significant abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
Medical conditions present at Screening (ie, before informed consent is obtained) or present 
before the first study treatment (Day -1 [Visit 1]) are not AEs and are not recorded on the AE 
CRF. These medical conditions should be adequately documented on the Medical History CRFs. 
Any increase in severity or frequency of a medical condition documented as medical history after 
first study treatment will be recorded as an AE and will be captured on the AE CRF. 
An uncomplicated pregnancy is not an AE or SAE and should not be reported as an AE/SAE. 
Subjects should be followed as described in Section 11.6. 
The reporting period for all non-serious AEs begins at the time of first study treatment (Day -1 
[Visit 1]) through Day 90 (Visit 9) and, if dosing in Cycle 2, from Day 180 [Visit 10] until Day 
270 [Visit 18]. Subjects who are withdrawn due to an AE should have an AE assessment 
completed 28 days or more after their last study drug injection. All AEs will be captured on the 
AE CRF. 
AEs should be documented in terms of a single medical diagnosis. When this is not possible, the 
AE should be documented in terms of signs and/or symptoms observed by the principal 
investigator or reported by the subject at each trial visit. 
If an AE is associated with or resulted from an overdose of IMP (for the purpose of this trial 
defined as more than twice the protocol-specified dose), it will be documented on the AE CRF 
and will also be reported to Dynavax or the Dynavax designee within 24 hours. Clinically 
significant laboratory abnormalities, as determined by the investigator, will be recorded as AEs. 
All related AEs observed during the trial are to be followed by the principal investigator until the 
AEs are resolved, or until the subject has completed the trial. Dynavax may request additional 
follow-up on specific unresolved events. 


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11.3.1 
Definition of Adverse Reaction 
An adverse reaction (AR) is defined as any AE caused by the use of a pharmaceutical product. 
ARs are a subset of all suspected AEs for which there is reason to conclude that the 
pharmaceutical product caused the event. 
11.3.2 
Definition of Suspected Adverse Reaction 
Suspected adverse reaction (SAR) means any AE for which there is a reasonable possibility that 
the study treatment caused the AE. “Reasonable possibility” means there is evidence to suggest a 
causal relationship between the study treatment and AE. An SAR implies a lesser degree of 
certainty about causality than AR, which means an AE caused by a study treatment. 
11.3.3 
Definition of Unexpected Adverse Event or Suspected Adverse Reactions 
An AE or SAR is considered “unexpected” if it is not listed in the Investigator Brochure or is not 
listed at the specificity or severity that has been previously observed. 
11.4 
Serious Adverse Events 
11.4.1 
Definition of Serious Adverse Events 
An AE is considered an SAE if it meets any of the following criteria: 
• Results in death 
• Is life-threatening 
Note:  An AE or SAR is considered “life-threatening” if, in the view of the either the 
investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an AE or SAR that, had it occurred in a more severe form, might 
have caused death. 
• Requires inpatient hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability or incapacity 
That is, the event severely or permanently disrupts the subject's ability to perform normal life 
functions or daily activities. 
• Results in a congenital anomaly or birth defect 
• Is medically significant (important medical event) 


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Medical and scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient. Examples 
of such events are allergic bronchospasm requiring treatment in an emergency room, serious 
blood dyscrasias or seizures/convulsions that do not result in hospitalization. The 
development of drug dependence or drug abuse would also be examples of important medical 
events. 
11.4.2 
Serious Adverse Event Reporting Requirements 
Any SAE that occurs from the time the consent is signed through completion of the subject’s 
participation in the study, whether or not the SAE is related to the investigational product, must 
be reported to Dynavax or its designee within 24 hours of investigator awareness of the 
event. The contact information for reporting SAEs is provided in the Study Reference Manual. 
General SAE reporting instructions are as follows: 
• Record all SAEs on the AE CRF 
• Submit SAE documents according to instructions in the Study Reference Manual 
• For SAEs, record the primary event on the AE CRF; describe events occurring secondary to 
that primary event on the SAE form in the narrative description of the case 
• Death is an outcome, not an event. Record the event that resulted in the death on the AE 
CRF. 
• For hospitalizations for surgical or diagnostic procedures, record the illness leading to the 
surgical or diagnostic procedure as the SAE, not the procedure itself. Capture the procedure 
in the narrative as part of the action taken in response to the illness 
• Elective hospitalizations will not be considered SAEs and do not need to be reported. 
However, complications that prolong elective hospitalizations should be recorded as SAEs. 
Emergency room visits of less than 24 hours do not meet the criterion of hospitalization for 
SAE reporting purposes. 
The report should contain, at a minimum, the following information: 
• Subject identifiers (ie, subject number) 
• Suspected medicinal product 
• AE term (must be listed as serious) 
• Contact information for person reporting event 
The relationship of the SAE to study treatment will be assessed by the investigator 
(Section 11.5.2). Follow-up information should be actively sought and submitted as it becomes 
available. 


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If the SAE is assessed as possibly or probably related to study treatment, it must be followed 
until it is considered stable or resolved. 
Any SAE assessed as not related to study treatment will be followed as clinically indicated until 
its resolution or, if non-resolving, until it is considered chronic or stable or until study 
completion. 
The investigator will assess relationship to study treatment. In addition, the sponsor will assess 
relationship to study treatment and determine expectedness based on the current Investigator 
Brochure. The sponsor’s determination of relatedness will define whether an event is a suspected 
unexpected serious adverse reaction (SUSAR). The sponsor will report all SUSARs to regulatory 
authorities as expedited reports in accordance with applicable regulatory requirements (21 Code 
of Federal Regulations [CFR] 312.32[c] in the US). All other SAEs will be reported as part of 
regulatory safety updates, as required, such as in annual reports. 
11.5 
Adverse Event Severity and Relationship to Study Treatment 
11.5.1 
Severity Grading of Adverse Events 
The severity of AEs will be graded based on adapted CTCAE, Version 4.03 (Table 11-1). 
Table 11-1: 
Common Terminology Criteria for Adverse Events (CTCAE, Version 
4.03) 
AE Severity 
Definition 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADLa. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADLb. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Source:  Adapted from CTCAE, Version 4.03 (National Cancer Institute 2010). 
ADL = activities of daily living; AE = adverse event. 
a 
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b 
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
For all AEs and SAEs, if there is a change in the severity after onset, the event should be 
reported as a single entry with the maximum severity grading captured. 


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11.5.2 
Relationship of Adverse Events to Study Treatment 
The investigator will determine the relationship of the AE to study treatment using the 
definitions provided in Table 11-2. 
Table 11-2: 
Definitions for Relationship of Adverse Events to Study Treatment 
Relationship to 
Study Treatment 
Definition 
Not Related 
Another cause of the event is most plausible; or clinically plausible temporal sequence is 
inconsistent with the onset of the event and the study treatment administration; or a 
causal relationship is considered biologically implausible. 
Possibly Related 
An event that follows a reasonable temporal sequence from administration of the study 
treatment or a known or expected response pattern to the suspected drug, but that could 
readily have been produced by a number of other factors. 
Probably Related 
An event that follows a reasonable temporal sequence from administration of the study 
treatment, and there is a biologically plausible mechanism for study treatment causing or 
contributing to the AE, and the event could not be reasonably explained by the known 
characteristics of the subject’s clinical state. In addition, the relationship may be 
confirmed by improvement on stopping the study treatment and reappearance of the 
event on repeated exposure. 
AE = adverse event. 
The investigator will follow all related AEs observed during the study until the AEs are 
considered resolved, or until the subject has completed the study. 
The investigator will follow all related SAEs observed during the study assessed as possibly or 
probably related to study treatment until the SAEs are considered stable or resolved. 
The sponsor may request additional follow-up on specific unresolved AEs. 
11.6 
Reporting and Documentation of Pregnancy 
Any subject who becomes pregnant during the study will be discontinued from study treatment 
and followed for pregnancy outcome. Follow-up information should be actively sought by the 
principal investigator and submitted to Dynavax or designee as soon as it becomes available. The 
principal investigator will complete the pregnancy reporting form and all other relevant CRFs. 
Uncomplicated pregnancies are not considered an AE/SAE. A complicated pregnancy or a 
pregnancy with an adverse outcome may meet criteria for an AE or SAE and would then also be 
reported according to the appropriate requirements. 
A subject who becomes pregnant will be instructed to report the pregnancy to the study site as 
soon as possible. A report of the pregnancy will be completed by the principal investigator or 
designee and will document details of the pregnancy, outcome of pregnancy, and details of 
delivery. The subject should be followed by the principal investigator through the remainder of 
the pregnancy for safety assessments. 


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The sponsor or designee must be notified as soon as possible once the study site learns of a 
pregnancy. Pregnancy report forms provided by the sponsor or designee must be completed and 
submitted to Dynavax or designee. The contact information for reporting pregnancy is provided 
in the Study Reference Manual. 
12.0 
STATISTICAL METHODS  
12.1 
General 
This trial is designed to allow preliminary assessments of safety and biological activity. No pre-
specified hypothesis testing will be performed. All analyses of demographics, biological activity, 
and safety will be descriptive. Details of statistical analyses for this study will be provided in the 
Statistical Analysis Plan. 
AEs, SAEs, and abnormal laboratory values will be summarized by the proportion of subjects 
who experience them. 
Response rate will be presented as the proportion of subjects who achieved CR or partial 
response (PR). Summary statistics will be provided for time to response, duration of response, 
TTP, and TTNT. 
In general, categorical data will be summarized as counts and percentages (or proportions) and 
continuous data will be summarized with descriptive statistics such as mean, standard deviation, 
median, minimum and maximum. 
Final analyses will be carried out after the last participant has completed the Final Study Visit, 
the study database has been authorized by Dynavax as complete and final, and major protocol 
deviations have been identified. Subject data will be reviewed for major protocol deviations by 
the Dynavax Medical Monitor prior to database lock. A listing of subjects with major protocol 
deviations will be provided, sorted by treatment and describing their deviations.


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12.2 
Sample-size Considerations 
This trial is designed to allow preliminary assessments of safety and biological activity in 
approximately 25 to 31 subjects. Thirteen subjects were enrolled in the dose escalation part of 
the trial and approximately 12 to 18 subjects are planned in the second part. Table 12-1 
summarizes the probabilities of detecting the number of responses if a total of 9 or 12 subjects 
(including subjects already enrolled in Phase 1) are enrolled in the target Phase 2 cohort. For 
example, if the true response rate is 30%, a sample size of 12 subjects will have 74% chance to 
obtain 3 or more responders and 50% chance to obtain 4 or more responders. A 90% exact 
binomial confidence interval will be constructed as preliminary efficacy information for further 
investigation. The numbers of responses and probabilities of detecting a response if total 
population size for a cohort is 9 or 12 subjects is provided in Table 12-1. 
Subjects who do not complete at least 4 injections for reasons other than discontinuation for 
toxicity or who do not have at least one post Screening assessment of tumor response may be 
replaced. 
Table 12-1: 
Probabilities of Detecting Response 
Number of Responses  
Probabilities of Detecting Response 
Subjects Enrolled  
(N=9) 
Subjects Enrolled  
(N=12) 
≥ 1 
95% 
98% 
≥ 2 
80% 
91% 
≥ 3 
53% 
74% 
≥ 4 
27% 
50% 
≥ 5 
9% 
27% 
12.3 
Study Analysis Populations 
The safety population will include all subjects who receive radiation treatment and at least one 
dose of SD-101. 
The efficacy population will include all subjects in the safety population who receive Screening 
imaging and bone marrow biopsy and at least one post baseline imaging assessment or who die 
prior to first post-baseline imaging. 
12.4 
 Demographic and Baseline Characteristics 
Demographic and baseline characteristics for the safety population will be listed by subject and 
summarized. Descriptive summary statistics (sample size, mean, median, standard deviation, and 
range, when appropriate) will be provided for the continuous variables such as age, weight, and 
height. Count and percentage will be reported for categorical variables such as sex, race, and 
ethnicity. 


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Age will be calculated between a subject's birth date and the date of his/her consent. 
12.5 
Pharmacokinetic and Pharmacodynamic Analyses 
The PK and PD population will consist of all subjects in the safety population who receive the 
second dose of SD-101 and have assessments at pre-dose through 24 hours post-dose. 
For PK, changes from pre-second dose to 24 hours post-second dose of SD-101 will be 
summarized by dose level. Maximum observed concentration (Cmax), time to reach Cmax (Tmax), 
half-life, and area under the concentration-time curve will be evaluated. 
IFN-alpha inducible genes will be assayed by quantitative polymerase chain reaction (qPCR) 
before administration of the first and second doses of SD-101 and after administration of 
SD-101. These genes will be assessed during Cycle 1 and, as applicable, Cycle 2. The fold 
increase will be analyzed as a surrogate for the activity of SD-101. The core group of genes 
measured will be ISG-54, Mx-B, IFN-alpha, TNF-alpha, IP-10, IRF-7, GBP-1, MCP-1, and 
MCP-2. Other genes may be tested to elucidate the patterns seen in the core genes. The fold 
increases will be analyzed per individual gene and as the geometric mean of their combination or 
a subset of the same. 
Additional analyses will include analysis of tumor samples (FNA) including analysis for RNA 
gene expression profiling and the analysis of immunologic related cells. The procedure for FNA 
collection is described in Section 10.9 and in the Laboratory Manual. 
12.6 
 Safety Analyses 
All safety data will be analyzed descriptively for the safety population. The most important 
safety parameters will be presented for all sites combined. Summary statistics will be used to 
describe the incidence of all injection-site reactions, AEs, SAEs, and deaths. DLTs occurring in 
Part 1 will be summarized by dose level received and presented in both tables and listings. 
12.7 
Response Analyses 
Rate of response of Lesion A and rate of response outside Lesion A will be analyzed 
descriptively and 90% exact binomial confidence interval will be calculated for both lesion 
response rates and overall response rate. Time to response and duration of response will be 
summarized for subjects who achieved CR or PR on study. Time to response is measured from 
first dose of SD-101 to CR or PR. Duration of response is measured from initial response (CR, 
PR) to progression or end of follow up for those who do not have disease progression. 
12.8 
 Interim Analysis 
No formal interim analysis is planned for this study. 


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13.0 
STUDY DOCUMENTATION AND DIRECT ACCESS 
13.1 
Source Documents 
The investigator must maintain detailed records of all study participants who are enrolled in the 
study or who undergo Screening. Source documents include, but are not limited to, subject 
medical records and investigator’s subject study files, as well as all test results. 
The following minimum information should be entered into the enrolled subject’s source 
documents: 
• The date the subject entered the study and the subject number 
• The study protocol number and the name Dynavax Technologies  
• The date that informed consent was signed 
• Evidence that the subject meets study eligibility requirements (eg, medical history, study 
procedures and/or evaluations) 
• The dates of all study-related subject visits 
• Evidence that study-required procedures and/or evaluations were completed 
• Use of any concurrent medications 
• Documentation of study medication accountability 
• Occurrence and status of any AEs 
• The date the subject exited the study, and a notation as to whether the subject completed the 
study or was discontinued early, including the reason for discontinuation 
• Any deviations from the protocol 
13.2 
Direct Access to Source Data/Documents 
Qualified individuals designated by Dynavax or its representative will monitor all aspects of the 
study at regular intervals throughout the study and following study completion. This monitoring 
is for the purpose of verifying adherence to the protocol including appropriate storage of IMP, 
completeness and exactness of the data being entered onto the CRFs, and compliance with 
United States Food and Drug Administration (FDA) or other regulatory agency regulations. The 
investigator and investigator’s institution agree to allow these monitors access to all study 
records, CRFs, and corresponding portions of the subject’s clinical study files; to allow access to 
the clinical supplies, dispensing, and storage areas; and if requested, to assist the monitors. The 
investigator further agrees to permit direct access to source data/documents for trial-related 
monitoring, audits, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
review, and regulatory inspection(s). 


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In certain circumstances, a secondary audit may be conducted by members of Dynavax’s Quality 
Assurance group or by Dynavax’s designated representative. The investigator will be notified if 
this is to take place, and advised as to the nature of the audit. 
14.0 
DATA QUALITY ASSURANCE 
The study sites will be monitored by Dynavax or its designee according to GCP and standard 
operating procedures. Prior to initiation of the study, representatives from Dynavax or its 
designee will review with the site personnel information about the investigational product, 
proper storage of IMP, protocol requirements, and monitoring requirements. During and after the 
study, periodic site visits will be made to monitor for compliance, including verification of the 
accuracy and completeness of data recorded on the CRFs, source documents, and IMP 
accountability records.  
15.0 
ETHICS 
15.1 
Institutional Review Board/Independent Ethics Committee 
The protocol and informed consent documents must be reviewed and approved by an 
appropriately composed IRB. The study will not be initiated at a site until appropriate written 
IRB approval of the protocol, ICF, and all recruiting materials (if applicable) is obtained by the 
investigator. Copies should be reviewed and approved by Dynavax prior to submission to the 
IRB. The investigator will submit periodic reports on the progress of the study as required by the 
IRB, in accordance with applicable governmental regulations, and in agreement with the policy 
established by Dynavax. In addition, the investigator will inform the IRB of any protocol 
amendments and administrative changes, and will obtain appropriate written IRB approval of all 
protocol amendments.  
15.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the protocol; GCP as defined in ICH guidelines 
and applicable local regulatory requirements.  
The study will be registered as a Phase 1/2 study on www.clinicaltrials.gov. 
15.3 
Informed Consent 
The investigator is responsible for obtaining informed consent from each subject participating in 
the study in compliance with US CFR Title 21, Part 50, Title 45 Part 46, and ICH and IRB 
guidelines. Prior to initiation of the study at the site, the ICF must be reviewed and accepted by 
Dynavax and approved by the governing IRB. The investigator or authorized designee will 
discuss the purpose and pertinent details of the study with each subject, and the subject must 
understand, sign, and date the appropriate IRB-approved ICF before undergoing any study-
specific procedures. The ICF must be personally signed and dated by the subject and by the 
person who conducted the informed consent discussion. Additional signature requirements may 
exist. The original signed and dated ICF will be retained with the subject’s study records, and a 


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copy of the signed ICF will be given to the subject. The investigator or designee will maintain a 
log of all subjects who sign the ICF. At a minimum, the log will include a subject identifier, the 
dates of informed consent and screening procedures, the outcome of the screening, and the 
reason the subject did not enroll in the trial. 
15.4 
Subject Confidentiality 
The investigator is responsible for maintaining the privacy and confidentiality of the subject’s 
medical or health information collected during the study. The investigator is also responsible for 
ensuring that all use, review and disclosure of subject’s medical or health information is in 
accordance with HIPAA regulations and the ICF approved by the IRB and signed by the subject. 
Specifically, all data collected about a subject during the study will be identified only by a 
number and the subject’s initials.  
16.0 
DATA HANDLING AND RECORD KEEPING 
16.1 
Case Report Forms 
Electronic case report forms (eCRF) will be used at the clinical trial site to collect trial data for 
enrolled subjects. Information on subjects who fail Screening, including demographic 
information and reason for screen fail, will be collected. The eCRFs are part of a controlled-
access EDC system managed by Dynavax or its authorized representative. Study staff with 
access to this EDC system will be trained prior to use. When data are available, authorized 
clinical trial site personnel will carefully and accurately record the data on the eCRF. The EDC 
system may be used to record original data and changes of data, with all changes tracked by the 
system in an electronic audit trail. Sites must ensure that all source documents are maintained 
according to ICH/GCP guidance and support the data that are entered onto the eCRFs. 
The eCRF data will be captured in a system validated according to procedures that comply with 
the applicable local legal and regulatory requirements and the ICH Guidelines for GCP (Topic 
E6, July 1996, Section 5.5.3). The eCRFs will be reviewed and signed by the investigator listed 
on FDA Form 1572 or applicable regulatory investigator agreement. After database lock, the 
investigator will receive a copy of the subject data for archiving at the study site. 
16.2 
Data Handling 
The sponsor will designate a CRO to perform data management. The CRO will write a data 
management plan outlining the data management systems, procedures, and agreements between 
the CRO and sponsor. The plan will be reviewed and signed by a representative of the sponsor’s 
data management department. 
Validation checks will be conducted to capture data errors, and data clarification queries will be 
generated at the time of data monitoring. Validation checks and queries will be issued to the 
investigational site for resolution, and the database will be updated to reflect query resolutions as 
appropriate. 


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Page 64 of 84 
Data verification against the source documents at the site will be performed by the sponsor or its 
designee prior to any interim analysis and prior to locking of the trial database. Following the 
completion of source data verification, a thorough review of data will be completed manually by 
the clinical data managers to ensure data consistency and to identify and request correction of 
any remaining data errors. All queries will be resolved or closed with written documentation 
providing reasons for irresolvable queries. Additional manual validation checks will be 
performed as needed. 
16.3 
Coding of Adverse Events, Drugs, and Diseases 
AEs and medical histories will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Prior and concomitant medications will be coded according to the World Health 
Organization Drug Dictionary (WHO Drug). 
16.4 
Record Retention 
The investigator must retain all records relating to the conduct of this study (including subject’s 
study records, receipt and disposition of all investigational materials, subject exclusion logs, 
signed consent forms, CRFs, all correspondence, and other supporting documentation) for at 
least 2 years after a marketing application for the drug is approved; or if an application is not 
filed or not approved for the drug, for at least 2 years after clinical development for the drug has 
been formally discontinued. However, in certain instances, documents may need to be retained 
for a longer period if required by regulatory requirements or by an agreement with Dynavax.  
The investigator may withdraw from the responsibility of retaining records only after transferring 
custody of the records to another individual who will accept responsibility for them. A written 
notice of transfer must be provided to Dynavax prior to or no later than 10 days after transfer.  
The investigator must allow representatives of the FDA, the governing IRB, or other regulatory 
agencies to inspect all study records. If informed of such an inspection, the investigator will 
notify Dynavax immediately. 
The investigator must obtain written approval from Dynavax prior to the destruction of any 
records relating to the conduct of this study. 
17.0 
USE OF INFORMATION AND PUBLICATION 
It is understood by the investigator that the information generated in this study is the property of 
Dynavax. It is understood that the investigator is obliged to provide Dynavax with complete test 
results, all study data, and access to all study records. 
All efforts should be made for abstracts and publications to be jointly authored by investigators 
and Dynavax. No publications based upon any preliminary study data shall occur prior to full 
completion of the clinical trial. Dynavax will be furnished with a copy of any other proposed 


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Page 65 of 84 
publication. Dynavax’s comments shall be given without undue delay, and not later than within 
60 days. 
Results from the investigation shall not be made available to any third party by the investigators 
or any of their staff. 
It is understood by the investigator that the information generated in this study may be used by 
Dynavax in connection with the development of the product and therefore may be disclosed to 
government agencies in various countries. To allow for the use of information derived from the 
study, it is understood that the investigator is obligated to provide Dynavax with complete test 
results, all study data, and access to all study records. 
Dynavax recognizes the importance of communicating medical study data, and therefore 
encourages their publication in reputable scientific journals and at seminars or conferences. 
Any results of medical investigations with Dynavax’s products and all publications, lectures, and 
manuscripts based thereon shall be exchanged and discussed by the investigators and Dynavax’s 
representatives prior to submission for publication or presentation. Due regard shall be given to 
Dynavax's legitimate interests, eg, manuscript authorship, obtaining optimal patent protection, 
coordinating and maintaining the proprietary nature of submissions to health authorities, 
coordinating with other ongoing studies in the same field, and protecting confidential data and 
information. 
Dynavax will be furnished with a copy of any proposed publication and allowed to make 
comments. In cases of publications or presentations of material arising from multicenter clinical 
investigations, Dynavax is to serve as coordinator and referee. Individual investigators who are 
part of a multicenter investigation may not publish or present data that are considered common to 
a multicenter investigation without the consent and the prior review of Dynavax. In case of 
disagreement among the investigators participating in a multicenter investigation, Dynavax will 
be the final arbiter. If Dynavax’s comments are not accepted, the senior author of the manuscript 
and Dynavax’s representatives shall promptly meet and endeavor to agree mutually on the final 
wording and disposition of the publication. The above procedure also applies to information on 
prematurely discontinued and other incomplete studies. 
Results from investigations shall not be made available to any third party by the investigating 
team outside the publication procedure as outlined previously. Dynavax will not quote from 
publications by investigators in its scientific information or promotional material without full 
acknowledgment of the source (ie, author and reference). 


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18.0 
REFERENCES 
Brennan, B. J., Xu, Z.X., Grippo, J.F. (2012). "Effect of peginterferon alfa-2a (40KD) on 
cytochrome P450 isoenzyme activity." 
Brody, J. D., W. Z. Ai, D. K. Czerwinski, J. A. Torchia, M. Levy, R. H. Advani, Y. H. Kim, R. 
T. Hoppe, S. J. Knox, L. K. Shin, I. Wapnir, R. J. Tibshirani and R. Levy (2010). "In situ 
vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study." J 
Clin Oncol 28(28): 4324-4332. 
Campbell, J. D., Y. Cho, M. L. Foster, H. Kanzler, M. A. Kachura, J. A. Lum, M. J. Ratcliffe, A. 
Sathe, A. J. Leishman, A. Bahl, M. McHale, R. L. Coffman and E. M. Hessel (2009). "CpG-
containing immunostimulatory DNA sequences elicit TNF-alpha-dependent toxicity in rodents 
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Center for Biologics Evaluation and Research (2007). Guidance for Industry: Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Trials, U.S. Department of Health and Human Services, Food and Drug Administration. 
Cheson, B. D., S. J. Horning, B. Coiffier, M. A. Shipp, R. I. Fisher, J. M. Connors, T. A. Lister, 
J. Vose, A. Grillo-Lopez, A. Hagenbeek, F. Cabanillas, D. Klippensten, W. Hiddemann, R. 
Castellino, N. L. Harris, J. O. Armitage, W. Carter, R. Hoppe and G. P. Canellos (1999). "Report 
of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI 
Sponsored International Working Group." J Clin Oncol 17(4): 1244. 
Cheson, B. D., B. Pfistner, M. E. Juweid, R. D. Gascoyne, L. Specht, S. J. Horning, B. Coiffier, 
R. I. Fisher, A. Hagenbeek, E. Zucca, S. T. Rosen, S. Stroobants, T. A. Lister, R. T. Hoppe, M. 
Dreyling, K. Tobinai, J. M. Vose, J. M. Connors, M. Federico and V. Diehl (2007). "Revised 
Response Criteria for Malignant Lymphoma." Journal of Clinical Oncology 25(5): 579-586. 
Duramad, O., K. L. Fearon, B. Chang, J. H. Chan, J. Gregorio, R. L. Coffman and F. J. Barrat 
(2005). "Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent 
death in vivo from systemic inflammation." J Immunol 174(9): 5193-5200. 
Guiducci, C., G. Ott, J. H. Chan, E. Damon, C. Calacsan, T. Matray, K. D. Lee, R. L. Coffman 
and F. J. Barrat (2006). "Properties regulating the nature of the plasmacytoid dendritic cell 
response to Toll-like receptor 9 activation." J Exp Med 203(8): 1999-2008. 
Harris, N. L., E. S. Jaffe, H. Stein, P. M. Banks, J. K. Chan, M. L. Cleary, G. Delsol, C. De 
Wolf-Peeters, B. Falini, K. C. Gatter and et al. (1994). "A revised European-American 
classification of lymphoid neoplasms: a proposal from the International Lymphoma Study 
Group." Blood 84(5): 1361-1392. 
Harris, N. L., S. H. Swerdlow, E. S. Jaffe, G. Ott, B. N. Nathwani, D. de Jong, T. Yoshino and 
D. Spagnolo (2008). Follicular lymphoma. WHO Classification of Tumours of Haematopoietic 
and Lymphoid Tissues. S. H. Swerdlow, E. Campo, N. L. Harris et al. Lyon, France, 
International Agency for Research on Cancer (IARC): 220-226. 


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Hervas-Stubbs, S., J. L. Perez-Gracia, A. Rouzaut, M. F. Sanmamed, A. Le Bon and I. Melero 
(2011). "Direct Effects of Type I Interferons on Cells of the Immune System." Clinical Cancer 
Research 17(9): 2619-2627. 
Honda, K., Y. Ohba, H. Yanai, H. Negishi, T. Mizutani, A. Takaoka, C. Taya and T. Taniguchi 
(2005). "Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon 
induction." Nature 434(7036): 1035-1040. 
Kawarada, Y., R. Ganss, N. Garbi, T. Sacher, B. Arnold and G. J. Hammerling (2001). "NK- and 
CD8(+) T cell-mediated eradication of established tumors by peritumoral injection of CpG-
containing oligodeoxynucleotides." J Immunol 167(9): 5247-5253. 
Kim, Y. H., D. Gratzinger, C. Harrison, J. D. Brody, D. K. Czerwinski, W. Z. Ai, A. Morales, F. 
Abdulla, L. Xing, D. Navi, R. J. Tibshirani, R. H. Advani, B. Lingala, S. Shah, R. T. Hoppe and 
R. Levy (2012). "In situ vaccination against mycosis fungoides by intratumoral injection of a 
TLR9 agonist combined with radiation: a phase 1/2 study." Blood 119(2): 355-363. 
Krieg, A. M. (2002). "CpG motifs in bacterial DNA and their immune effects." Annu Rev 
Immunol 20: 709-760. 
Krieg, A. M. (2006). "Therapeutic potential of Toll-like receptor 9 activation." Nat Rev Drug 
Discov 5(6): 471-484. 
Krieg, A. M., A. K. Yi, S. Matson, T. J. Waldschmidt, G. A. Bishop, R. Teasdale, G. A. 
Koretzky and D. M. Klinman (1995). "CpG motifs in bacterial DNA trigger direct B-cell 
activation." Nature 374(6522): 546-549. 
Kuramoto, E., O. Yano, Y. Kimura, M. Baba, T. Makino, S. Yamamoto, T. Yamamoto, T. 
Kataoka and T. Tokunaga (1992). "Oligonucleotide sequences required for natural killer cell 
activation." Jpn J Cancer Res 83(11): 1128-1131. 
Lou, Y., C. Liu, G. Lizee, W. Peng, C. Xu, Y. Ye, B. A. Rabinovich, Y. Hailemichael, A. 
Gelbard, D. Zhou, W. W. Overwijk and P. Hwu (2011). "Antitumor activity mediated by CpG: 
the route of administration is critical." J Immunother 34(3): 279-288. 
Mirzaie-Joniani, H., D. Eriksson, A. Sheikholvaezin, A. Johansson, P.-O. Löfroth, L. Johansson 
and T. Stigbrand (2002). "Apoptosis induced by low-dose and low-dose-rate radiation." Cancer 
94(S4): 1210-1214. 
National Cancer Institute (2010). Common Terminology Criteria for Adverse Events (CTCAE), 
Version 4.03. National Cancer Institute, National Institutes of Health, U.S. Department of Health 
and Human Services. 
National Cancer Institute. (2014). "SEER Cancer Statistics Factsheets: Non-Hodgkin 
Lymphoma."   Retrieved 28Mar2014, from http://seer.cancer.gov/statfacts/html/nhl.html  
 


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Oken, M. M., R. H. Creech, D. C. Tormey, J. Horton, T. E. Davis, E. T. McFadden and P. P. 
Carbone (1982). "Toxicity and response criteria of the Eastern Cooperative Oncology Group." 
Am J Clin Oncol 5(6): 649-655. 
Roman, M., E. Martin-Orozco, J. S. Goodman, M. D. Nguyen, Y. Sato, A. Ronaghy, R. S. 
Kornbluth, D. D. Richman, D. A. Carson and E. Raz (1997). "Immunostimulatory DNA 
sequences function as T helper-1-promoting adjuvants." Nat Med 3(8): 849-854. 
Solal-Celigny, P., P. Roy, P. Colombat, J. White, J. O. Armitage, R. Arranz-Saez, W. Y. Au, M. 
Bellei, P. Brice, D. Caballero, B. Coiffier, E. Conde-Garcia, C. Doyen, M. Federico, R. I. Fisher, 
J. F. Garcia-Conde, C. Guglielmi, A. Hagenbeek, C. Haioun, M. LeBlanc, A. T. Lister, A. 
Lopez-Guillermo, P. McLaughlin, N. Milpied, P. Morel, N. Mounier, S. J. Proctor, A. Rohatiner, 
P. Smith, P. Soubeyran, H. Tilly, U. Vitolo, P. L. Zinzani, E. Zucca and E. Montserrat (2004). 
"Follicular lymphoma international prognostic index." Blood 104(5): 1258-1265. 
Tokunaga, T., O. Yano, E. Kuramoto, Y. Kimura, T. Yamamoto, T. Kataoka and S. Yamamoto 
(1992). "Synthetic oligonucleotides with particular base sequences from the cDNA encoding 
proteins of Mycobacterium bovis BCG induce interferons and activate natural killer cells." 
Microbiol Immunol 36(1): 55-66. 
Yamamoto, S., E. Kuramoto, S. Shimada and T. Tokunaga (1988). "In vitro augmentation of 
natural killer cell activity and production of interferon-alpha/beta and -gamma with 
deoxyribonucleic acid fraction from Mycobacterium bovis BCG." Jpn J Cancer Res 79(7): 866-
873. 
 
 


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APPENDIX 1: 
SCHEDULE OF STUDY ASSESSMENTS (PART 1 ONLY) 
Trial Period: 
Screening 
Treatment 
Follow-up 
EDa 
UNSb 
Procedure: 
Visit: 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
ED 
UNS 
Day: 
- 30 to -2 
-1 
1 
8 
9c 
15 
22 
29 
36 
90 
180 
360 
540 
720 
 
 
Visit Window (days): 
 
 
 
 
 
 
 
 
±3 
±14 
±14 
±14 
±14 
±14 
 
 
 
 
 
DLT Evaluation Periodd 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary carde 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Medical and medication history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signsf,w 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
Physical examinationg,w 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogramw  
X 
 
 
 
 
Xh 
 
 
X 
 
 
 
 
 
 
 
HIV and hepatitis testingi,w, y  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistryj,w, y 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyk,w, y 
X 
X 
 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulationl,w, y  
X 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
X 
 
Pregnancy testingm, y 
X 
X 
 
X 
 
X 
X 
X 
 
 
 
 
 
 
X 
 
Unilateral bone marrow biopsy and aspirate n  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Localized XRT 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD-101 intratumoral injectionz 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Post-treatment observation (minimum 30 minutes) 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Injection-site reaction assessment 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Blood for IFN-alpha inducible gene expression (PD) o  
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for RNA to study gene expression changesp  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Fine needle aspirateq  
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
X 
 


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APPENDIX 1: 
SCHEDULE OF STUDY ASSESSMENTS (PART 1 ONLY) (CONT’D) 
Trial Period: 
Screening 
Treatment 
Follow-up 
EDa UNSb 
Procedure: 
Visit: 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
ED 
UNS 
Day: 
- 30 to -2 
-1 
1 
8 
9c 
15 
22 
29 
36 
90 
180 
360 
540 
720 
 
 
Visit Window (days): 
 
 
 
 
 
 
 
 
±3 
±14 
±14 
±14 
±14 
±14 
 
 
 
 
 
DLT Evaluation Periodd 
 
 
 
 
 
 
 
Serum for anti-dsDNAx, y 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
Serum for anti-SD-101 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
Plasma for pharmacokineticsr 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Reserve serum aliquots  
 
X 
 
X 
X 
 
X 
 
X 
 
 
 
 
 
X 
 
CT Scan (Neck/Chest/Abdomen/Pelvis)t 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Eventsu  
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
Serious Adverse Events  
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medicationsv  
 
X 
X 
X 
 
X 
X 
X 
X 
Xv 
Xv 
Xv 
Xv 
Xv 
Xv 
 


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Page 71 of 84 
APPENDIX 1: 
SCHEDULE OF STUDY ASSESSMENTS (PART 1 ONLY) (CONT’D) 
FOOTNOTES 
AE = adverse event; ALT = alanine aminotransferase; anti-dsDNA = antibodies to double-stranded deoxyribonucleic acid; APTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; Cr = creatinine; CR = complete response; CRP = C-reactive protein; CT = computed tomography; D = Day; DLT = dose-limiting toxicity; ED = early 
discontinuation; FNA = fine needle aspiration; GGT = gamma-glutamyl transpeptidase; HBc = hepatitis B core antigen; HCV = hepatitis C virus; Hgb = hemoglobin; HIV = human immunodeficiency 
virus; IFN = interferon; IMP = investigational medicinal product; LDH = lactate dehydrogenase; PD = pharmacodynamics; PET/CT = Positron Emission Tomography/computed tomography; 
PK = pharmacokinetics; PT = prothrombin time; RNA = ribonucleic acid; SAE = serious adverse event; SOC = standard of care; UNS = unscheduled visit; WBC = white blood cell; 
WOCBP = women of childbearing potential; XRT = radiation therapy. 
a 
Every effort should be made to complete the ED visit within a window no later than the next scheduled study visit (and at least 7 days following the last injection). Subjects who are withdrawn 
due to an AE should be followed for up to 28 days or more after their last dose of study drug. If the subject is discontinuing study, the ED can be performed at the same visit as the AE 
assessment. 
b 
An unscheduled visit should be performed if there is suspected disease progression or subject safety concerns. If disease progression is suspected, it must be reported to the sponsor within 24 
hours (Section 8.4) and confirmation of disease progression should be documented by completing a targeted physical examination (including assessment of the liver and Spleen) based on subject-
reported symptoms including vital signs (heart rate, blood pressure, respiratory rate), serum chemistry, hematology, CT scan, and unilateral bone marrow biopsy and aspirate if clinically 
indicated by new abnormalities in the peripheral blood counts or blood smear (Section 8.4). Fine needle aspirate samples are only to be collected at an unscheduled visit if the ±21 days visit 
window at Visit 8 is used or at a visit to assess disease progression. If an unscheduled visit is performed because of a safety concern related to IMP, at a minimum, the following should be 
performed:  a targeted physical examination based on subject-reported symptoms including vital signs (heart rate, blood pressure, and respiratory rate), serum chemistry, and hematology. 
c  
The Day 9 visit (Visit 4) must occur 1 day (24 ± 3 hours) after the Day 8 (Visit 3) visit. 
d 
DLT evaluation will be based on review of safety data through 7 days following the end of treatment (Day 36 [Visit 8] or ED). 
e 
A new diary card should be issued at Visits 2, 3, 5, 6 and 7 prior to study injection. Diary cards should be reviewed for injection site reactions and solicited AEs at Visits 3, 5, 6, 7, and 8. 
f 
Includes oral temperature (only at study injection visits), heart rate, respiratory rate, and systolic and diastolic blood pressure. 
g 
The investigator or qualified designee will conduct physical examinations. A complete physical examination is conducted at Screening and ED, and a targeted physical examination (based on 
interval history and/or AEs) is conducted at all other visits. Assessment of the liver and spleen must be done during the physical exams that are completed at Screening, Day 90, Day 180, Day 
360, Day 540, Day 720, Unscheduled Visit and ED Visit, where lesions are evaluated and the Cheson criteria are used to assess overall response. 
h 
Electrocardiogram on Day 15 to be performed after SD-101 dosing. 
i 
Hepatitis and HIV testing to include hepatitis B surface antigen, anti-HBc, anti-HCV, and anti-HIV. 
j 
Chemistry (includes sodium, potassium, chloride, bicarbonate, BUN, Cr, glucose, calcium, AST, ALT, GGT, LDH, bilirubin, alkaline phosphatase) and CRP. 
k 
Includes Hgb, hematocrit, WBC count with differential, and platelet count. 
l 
Includes PT and APTT.


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Page 72 of 84 
APPENDIX 1: 
SCHEDULE OF STUDY ASSESSMENTS (PART 1 ONLY) (CONT’D) 
FOOTNOTES (CONT’D) 
m 
For WOCBP, serum pregnancy testing will be conducted at Screening and serum or urine pregnancy test at subsequent visits. Serum or urine pregnancy must be negative prior to study treatment. 
Dipstick can be used. All female subjects are considered to be WOCBP except as defined in Section 5.3. 
n 
Unilateral bone marrow biopsy and aspirates will be performed at Screening if not previously performed or if performed more than 90 days previously with negative results. The bone marrow 
biopsy will be performed to confirm a CR if the subject was initially positive or if it is clinically indicated by new abnormalities in the peripheral blood counts or blood smear (Section 8.4). 
o 
IFN-inducible gene expression measured at Day -1 (Visit 1, baseline) prior to radiation, at Day 1 (Visit 2) prior to injection, at Day 8 (Visit 3) prior to injection, and at Day 9 (Visit 4) which is 24 
(± 3) hours after injection. 
p 
Blood for RNA analysis is to be collected pre-injection on treatment days. 
q 
FNA samples will be collected from Lesion A at Visit 1 and 3. Collection of FNA samples from 1 or more additional lesions, if accessible, is encouraged but is optional. Collection of FNA 
samples at Visit 8 and a visit to assess disease progression is optional. Collections are to be done pre-XRT or pre-injection on treatment days. The Day 36 sample can be collected ±21 days from 
Visit 8. 
r 
Plasma PK samples will be obtained pre-dose; 1, 2, 4, and 6 hours (± 10 minutes) post-dose (Visit 3); and 24 (± 3) hours post-dose (Visit 4) in Part 1 only. 
s 
An extra aliquot of serum will be collected and stored frozen for possible future testing. 
t 
PET scans will only be permitted if PET/CT is the SOC at the participating institution. Perform a CT scan of neck, chest, abdomen, pelvis and other areas as clinically indicated at all imaging 
timepoints. 
u 
The AE assessment at the ED Visit should occur 7 days or more after the subject’s last study injection. Subjects who are withdrawn due to a AE should have an AE assessment completed 28 days 
or more after the last study drug injection. If the subject is discontinuing study, the ED can be performed at the same visit as the AE assessment. 
v 
All concomitant medications taken by the subject from Screening through Day 90 (Visit 9) will be reported. Concomitant medications used to treat an SAE or immunomodulator drugs taken after 
Day 90 (Visit 9) through Day 720 (Visit 13) or ED are also to be reported. 
w 
Results from SOC assessments completed within 30 days prior to a subject signing informed consent, may be used in lieu of repeating those study procedures during the 28 day Screening 
window:  vital signs, physical exam, electrocardiogram, hepatitis and HIV testing, chemistry, hematology, coagulation. In addition, a copy of a record of lesion size at a timepoint at least 3 
months prior to baseline should be added to the subject’s CRF. 
x 
Quantitative results for anti-dsDNA are required. 
y 
All safety laboratory tests are to be performed at the local laboratory. 
z 
The treated lesion should be labeled as Lesion A. The same lesion should be injected throughout Cycle 1, and if the lesion regresses, SD-101 should be injected into a peritumoral area. 
 
 


Dynavax Technologies Corporation 
 
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CONFIDENTIAL AND PROPRIETARY 
Page 73 of 84 
APPENDIX 2: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 1 TREATMENT CYCLE) 
Trial Period: 
Screening 
Treatment - Cycle 1 
Follow-up 
EDa 
UNSb 
Procedure: 
Visit: 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
ED 
UNS 
Day: 
- 30 to -2 
-1 
1 
8 
9c 
15 
22 
29 
36 
90 
180 
360 
540 
720 
 
 
Visit Window (days): 
 
 
 
±1 
 
±1 
±1 
±1 
±3 
±14 
±14 
±14 
±14 
±14 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary cardd 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Medical and medication history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signse, f 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
X 
X 
Physical examinationf,g 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogramf 
X 
 
 
 
 
Xh 
 
 
X 
 
 
 
 
 
 
 
HIV and hepatitis testingf,i,t 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistryf,j,t 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Hematologyf,k,t 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulationf,l,t 
X 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
X 
 
Pregnancy testingm, t 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unilateral bone marrow biopsy and aspirate n  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Localized XRT 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
SD-101 intratumoral injectiony  
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Post-treatment observation (minimum 30 minutes) 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Injection-site reaction assessment 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Blood for IFN-alpha inducible gene expression (PD) o 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for RNA to study gene expression changesp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Fine needle aspirate of treated lesion (Lesion A)q 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
Fine needle aspirate of untreated lesion (Lesion B)r 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 74 of 84 
APPENDIX 2: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 1 TREATMENT CYCLE) 
(CONT’D) 
Trial Period: 
Screening 
Treatment - Cycle 1 
Follow-up 
EDa 
UNSb 
Procedure: 
Visit: 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
ED 
UNS 
Day: 
- 30 to -2 
-1 
1 
8 
9c 
15 
22 
29 
36 
90 
180 
360 
540 
720 
 
 
Visit Window (days): 
 
 
 
±1 
 
±1 
±1 
±1 
±3 
±14 
±14 
±14 
±14 
±14 
 
 
Serum for anti-dsDNAs,t 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
Serum for anti-SD-101 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
Reserve serum aliquotu  
 
X 
 
X 
 
 
X 
 
X 
 
 
 
 
 
X 
 
CT Scan (Neck/Chest/Abdomen/Pelvis)v 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Eventsw 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
X 
 
Serious Adverse Events  
 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medicationsx 
 
X 
X 
X 
 
X 
X 
X 
X 
Xx 
Xx 
Xx 
Xx 
Xx 
Xx 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 75 of 84 
APPENDIX 2: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 1 TREATMENT CYCLE) 
(CONT’D) 
FOOTNOTES 
AE = adverse event; ALT = alanine aminotransferase; anti-dsDNA = antibodies to double-stranded deoxyribonucleic acid; APTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; Cr = creatinine; CR = complete response; CRP = C-reactive protein; CT = computed tomography; D = Day; DLT = dose-limiting toxicity; ED = early 
discontinuation; FNA = fine needle aspiration; GGT = gamma-glutamyl transpeptidase; HBc = hepatitis B core antigen; HCV = hepatitis C virus; Hgb = hemoglobin; HIV = human immunodeficiency 
virus; IFN = interferon; IMP = investigational medicinal product; LDH = lactate dehydrogenase; PD = pharmacodynamics; PET/CT = Positron Emission Tomography/computed tomography; PT = 
prothrombin time; RNA = ribonucleic acid; SAE = serious adverse event; SOC = standard of care; UNS = unscheduled visit;; WBC = white blood cell; WOCBP = women of childbearing potential; 
XRT = radiation therapy. 
a 
Every effort should be made to complete the ED visit within a window no later than the next scheduled study visit (and at least 7 days following the last injection). Subjects who are withdrawn 
due to an AE should be followed for up to 28 days or more after their last dose of study drug. If the subject is discontinuing study, the ED can be performed at the same visit as the AE 
assessment. 
b 
An unscheduled visit should be performed if there is suspected disease progression or subject safety concerns. If disease progression is suspected, it must be reported to the sponsor within 24 
hours (Section 8.4) and confirmation of disease progression should be documented by completing a targeted physical examination (including assessment of the Liver and Spleen) based on 
subject-reported symptoms including vital signs (heart rate, blood pressure, respiratory rate), serum chemistry, hematology, CT scan, and unilateral bone marrow biopsy and aspirate if clinically 
indicated by new abnormalities in the peripheral blood counts or blood smear (Section 8.4). Fine needle aspirate samples are only to be collected at an unscheduled visit if the ±21 days visit 
window at Visit 8 is used or at a visit to assess disease progression. If an unscheduled visit is performed because of a safety concern related to IMP, at a minimum, the following should be 
performed:  a targeted physical examination based on subject-reported symptoms including vital signs (heart rate, blood pressure, and respiratory rate), serum chemistry, and hematology. 
c  
The Day 9 visit (Visit 4) must occur 1 day (24 ± 3 hours) after the Day 8 (Visit 3) visit. 
d 
A new diary card should be issued at Visits 2, 3, 5, 6 and 7 prior to study injection. Diary cards should be reviewed for injection site reactions and solicited AEs at Visits 3, 5, 6, 7, and 8. 
e 
Includes oral temperature (only at study injection visits), heart rate, respiratory rate, and systolic and diastolic blood pressure. 
f 
Results from SOC assessments completed within 30 days prior to a subject signing informed consent, may be used in lieu of repeating those study procedures during the 28-day Screening 
window:  vital signs, physical exam, electrocardiogram, hepatitis and HIV testing, chemistry, hematology, coagulation. In addition, a copy of a record of lesion size at a timepoint at least 3 
months prior to baseline should be added to the subject’s CRF. 
g 
The investigator or qualified designee will conduct physical examinations. A complete physical examination is conducted at Screening and ED, and a targeted physical examination (based on 
interval history and/or AEs) is conducted at all other visits. Assessment of the liver and spleen must be done during the physical exams that are completed at Screening, Day 90, Day 180, Day 
360, Day 540, Day 720, Unscheduled Visit and ED Visit, where lesions are evaluated and the Cheson criteria are used to assess overall response. 
h 
Electrocardiogram on Day 15 to be performed after SD-101 dosing. 
i 
Hepatitis and HIV testing to include hepatitis B surface antigen, anti-HBc, anti-HCV, and anti-HIV. 
j 
Chemistry (includes sodium, potassium, chloride, bicarbonate, BUN, Cr, glucose, calcium, AST, ALT, GGT, LDH, bilirubin, alkaline phosphatase) and CRP.  
k 
Includes Hgb, hematocrit, WBC count with differential, and platelet count. 
l 
Includes PT and APTT. 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 76 of 84 
APPENDIX 2: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 1 TREATMENT CYCLE) 
(CONT’D) 
FOOTNOTES (CONT’D) 
m 
For WOCBP, serum pregnancy testing will be conducted at Screening. Serum or urine pregnancy must be negative prior to initiation of study treatment. All female subjects are considered to be 
WOCBP except as defined in Section 5.3.  
n 
Unilateral bone marrow biopsy and aspirates will be performed at Screening if not previously performed or if performed more than 90 days previously with negative results. The bone marrow 
biopsy will be performed to confirm a CR if the subject was initially positive or if it is clinically indicated by new abnormalities in the peripheral blood counts or blood smear (Section 8.4). 
o 
IFN-inducible gene expression measured at Day -1 (Visit 1, baseline) prior to radiation, at Day 1 (Visit 2) prior to injection, at Day 8 (Visit 3) prior to injection, and at Day 9 (Visit 4) which is 24 
(± 3) hours after injection. 
p 
Blood for RNA analysis is to be collected pre-injection on treatment days. 
q 
Two FNA samples will be collected from Lesion A on Day -1, Day 8 (Visit 3), and Day 36 (Visit 8). Collections are to be done pre-XRT or pre-injection on treatment days. There is a ± 21 day 
window for the FNA sample collection at Day 36.  
r 
Collection of 2 FNA samples from Lesion B, on Day -1, Day 36 (Visit 8), and Day 90 (Visit 9). Collections are to be done pre-XRT or pre-injection on treatment days. There is a ± 21 day 
window for the FNA sample collection at Day 90. 
s 
Quantitative results for anti-dsDNA are required. 
t 
All safety laboratory tests are to be performed at the local laboratory. 
u 
An extra aliquot of serum will be collected and stored frozen for possible future testing. 
v 
PET scans will only be permitted if PET/CT is the SOC at the participating institution. Perform a CT scan of neck, chest, abdomen, pelvis and other areas as clinically indicated at all imaging 
timepoints. 
w 
The AE assessment at the ED Visit should occur 7 days or more after the subject’s last study injection. Subjects who are withdrawn due to a AE should have an AE assessment completed 28 days 
or more after the last study drug injection. If the subject is discontinuing study, the ED can be performed at the same visit as the AE assessment. 
x 
All concomitant medications taken by the subject from Screening through Day 90 (Visit 9) will be reported. Concomitant medications used to treat an SAE or immunomodulator drugs taken after 
Day 90 (Visit 9) through Day 720 (Visit 13) or ED are also to be reported. 
y 
The treated lesion should be labeled as Lesion A. The same lesion should be injected throughout Cycle 1, and if the lesion regresses, SD-101 should be injected into a peritumoral area. 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 77 of 84 
APPENDIX 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 2 TREATMENT CYCLES) 
Trial Period: 
Screening Treatment - Cycle 1 Follow-up 
Treatment - Cycle 2 
Follow-up 
EDa UNSb 
Procedure: 
Visit: 
Screen 
1 2 3 4 5 6 7 
8 
9 
10 
11 
12 13 14 15 
16 
17 
18 
19 
20 
21 ED UNS 
Day: - 30 to -2 -1 1 8 9c 15 22 29 36 
90 
180 y 181y 188 189 195 202 209 216 270 360 540 720 
 
 
Visit Window (days): 
 
 
 ±1  ±1 ±1 ±1 ±3 ±14 
±14 
 
±1 
 
±1 ±1 
±1 
±3 ±14 ±14 ±14 ±14 
 
 
Informed consenty 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary cardd 
 
 X X  X X X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and medication history 
X 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signse, f 
X 
X X X  X X X 
X 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
X 
X 
Physical examinationf,g 
X 
X  
 
 
 
X 
 
X 
X 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogramf 
X 
 
 
 
 Xh  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV and hepatitis testingf,i,t 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistryf,j,t,z 
X 
X  
 
 
 
X 
 
X 
X 
X 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
Hematologyf,k,t,z 
X 
X  X  X X X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulationf,l,t,z 
X 
X  
 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
Pregnancy testingm, t 
X 
 
 
 
 
 
 
 
 
 
Xm 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unilateral bone marrow biopsy and aspiraten  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Localized XRTy 
 
X X  
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
SD-101 intratumoral injectiony 
 
 X X  X X X 
 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
Post-treatment observation (minimum 30 minutes) 
 
 X X  X X X 
 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
Injection-site reaction assessment 
 
 X X  X X X 
X 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
Blood for IFN-alpha inducible gene expression (PD)o 
 
X X X X  
 
 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Blood for RNA to study gene expression changesp 
X 
X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Fine needle aspirate of treated Lesionq 
 
X  X 
 
 
 
 
X 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
Fine needle aspirate of untreated Lesionr 
 
X  
 
 
 
 
 
X 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 78 of 84 
APPENDIX 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 2 TREATMENT CYCLES) 
(CONT’D) 
Trial Period: 
Screening Treatment - Cycle 1 Follow-up 
Treatment - Cycle 2 
Follow-up 
EDa UNSb 
Procedure: 
Visit: 
Screen 
1 2 3 4 5 6 7 
8 
9 
10 
11 
12 13 14 15 
16 
17 
18 
19 
20 
21 ED UNS 
Day: - 30 to -2 -1 1 8 9c 15 22 29 36 
90 
180 y 181y 188 189 195 202 209 216 270 360 540 720 
 
 
Visit Window (days): 
 
 
 ±1  ±1 ±1 ±1 ±3 ±14 
±14 
 
±1 
 
±1 ±1 
±1 
±3 ±14 ±14 ±14 ±14 
 
 
Serum for anti-dsDNAs,t 
 
X  
 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
Serum for anti-SD-101 
 
X  
 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
 
 
 
Reserve serum aliquotu  
 
X  X  
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
 
 
 
X 
 
CT Scan (Neck/Chest/Abdomen/Pelvis)v 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Adverse Eventsw 
 
X X X  X X X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
X 
 
Serious Adverse Events  
 
X X X  X X X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medicationsx 
 
X X X  X X X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 79 of 84 
APPENDIX 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 2 TREATMENT CYCLES) 
(CONT’D) 
FOOTNOTES 
AE = adverse event; ALT = alanine aminotransferase; anti-dsDNA = antibodies to double-stranded deoxyribonucleic acid; APTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; Cr = creatinine; CR = complete response; CRP = C-reactive protein; CT = computed tomography; D = Day; DLT = dose-limiting toxicity; ED = early 
discontinuation; FNA = fine needle aspiration; GGT = gamma-glutamyl transpeptidase; HBc = hepatitis B core antigen; HCV = hepatitis C virus; Hgb = hemoglobin; HIV = human immunodeficiency 
virus; IFN = interferon; IMP = investigational medicinal product; LDH = lactate dehydrogenase; PD = pharmacodynamics PET/CT = Positron Emission Tomography/computed tomography; PT = 
prothrombin time; RNA = ribonucleic acid; SAE = serious adverse event; SOC = standard of care; UNS = unscheduled visit;; WBC = white blood cell; WOCBP = women of childbearing potential; 
XRT = radiation therapy. 
a 
Every effort should be made to complete the ED visit within a window no later than the next scheduled study visit (and at least 7 days following the last injection). Subjects who are withdrawn 
due to an AE should be followed for up to 28 days or more after their last dose of study drug. If the subject is discontinuing study, the ED can be performed at the same visit as the AE 
assessment. 
b 
An unscheduled visit should be performed if there is suspected disease progression or subject safety concerns. If disease progression is suspected, it must be reported to the sponsor within 24 
hours (Section 8.4) and confirmation of disease progression should be documented by completing a targeted physical examination (including assessment of the Liver and Spleen) based on 
subject-reported symptoms including vital signs (heart rate, blood pressure, respiratory rate), serum chemistry, hematology, CT scan, and unilateral bone marrow biopsy and aspirate if clinically 
indicated by new abnormalities in the peripheral blood counts or blood smear (Section 8.4). Fine needle aspirate samples are only to be collected at an unscheduled visit if the ±21 days visit 
window at Visit 8 is used or at a visit to assess disease progression. If an unscheduled visit is performed because of a safety concern related to IMP, at a minimum, the following should be 
performed:  a targeted physical examination based on subject-reported symptoms including vital signs (heart rate, blood pressure, and respiratory rate), serum chemistry, and hematology. 
c  
The Day 9 visit (Visit 4) must occur 1 day (24 ± 3 hours) after the Day 8 (Visit 3) visit. 
d 
A new diary card should be issued at Visits 2, 3, 5, 6 and 7 prior to study injection. Diary cards should be reviewed for injection site reactions and solicited AEs at Visits 3, 5, 6, 7, and 8. 
e 
Includes oral temperature (only at study injection visits), heart rate, respiratory rate, and systolic and diastolic blood pressure. 
f 
Results from SOC assessments completed within 30 days prior to a subject signing informed consent, may be used in lieu of repeating those study procedures during the 28-day Screening 
window:  vital signs, physical exam, electrocardiogram, hepatitis and HIV testing, chemistry, hematology, coagulation. In addition, a copy of a record of lesion size at a timepoint at least 3 
months prior to baseline should be added to the subject’s CRF. 
g 
The investigator or qualified designee will conduct physical examinations. A complete physical examination is conducted at Screening and ED, and a targeted physical examination (based on 
interval history and/or AEs) is conducted at all other visits. Assessment of the liver and spleen must be done during the physical exams that are completed at Screening, Day 90, Day 180, Day 
360, Day 540, Day 720, Unscheduled Visit and ED Visit, where lesions are evaluated and the Cheson criteria are used to assess overall response. 
h 
Electrocardiogram on Day 15 to be performed after SD-101 dosing. 
i 
Hepatitis and HIV testing to include hepatitis B surface antigen, anti-HBc, anti-HCV, and anti-HIV. 
j 
Chemistry (includes sodium, potassium, chloride, bicarbonate, BUN, Cr, glucose, calcium, AST, ALT, GGT, LDH, bilirubin, alkaline phosphatase) and CRP. 
k 
Includes Hgb, hematocrit, WBC count with differential, and platelet count. 
l 
Includes PT and APTT. 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 80 of 84 
APPENDIX 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 2 TREATMENT CYCLES) 
(CONT’D) 
FOOTNOTES (CONT’D) 
m 
For WOCBP, serum pregnancy testing will be conducted at Screening. Serum or urine pregnancy must be negative prior to initiation of Cycle 1 study treatment and within 3 days prior to 
initiation of Cycle 2 study treatment. Study treatment consists of localized low-dose radiation and SD-101 injections. All female subjects are considered to be WOCBP except as defined in 
Section 5.3. 
n 
Unilateral bone marrow biopsy and aspirates will be performed at Screening if not previously performed or if performed more than 90 days previously with negative results. UNS bone marrow 
biopsy will be performed only if indicated per SOC. The bone marrow biopsy will be performed to confirm a CR if the subject was initially positive or if it is clinically indicated by new 
abnormalities in the peripheral blood counts or blood smear (Section 8.4). 
o 
IFN-inducible gene expression measured at Day -1 (Visit 1, baseline) prior to radiation, at Day 1 (Visit 2) prior to injection, at Day 8 (Visit 3) prior to injection, and at Day 9 (Visit 4) which is 24 
(± 3) hours after injection. 
p 
Blood for RNA analysis is to be collected pre-injection on treatment days. 
q 
In Part 2, Treatment Cycle 1, the collection of 2 FNA samples are required from an treated lesion (Lesion A) on Day -1 (Visit 1), Day 8 (Visit 3), and Day 36 (Visit 8). In Part 2 Treatment Cycle 
2, a single FNA sample will be collected from the Treatment Cycle 2 treated lesion on Day 180 (Visit 10), Day 188 (Visit 12), and Day 216 (Visit 17). Collections are to be done pre-XRT or pre-
injection on treatment days. There is a ± 21 day window for the FNA sample collection at Day 36 and Day 216. 
r 
In Part 2, Treatment Cycle 1, the collection of 2 FNA samples each are required from an untreated lesion (Lesion B) on Day -1 (Visit 1), Day 36 (Visit 8), and Day 90 (Visit 9). 
 
For Part 2, Treatment Cycle 2, a single FNA of an untreated lesion may be collected on Day 180 (Visit 10), Day 216 (Visit 17) and Day 270 (Visit 18). The untreated lesion must be selected 
outside the field of radiation of the treated lesion. There is a ± 21 day window for the FNA sample collection at Day 90 and Day 270. If there is no accessible untreated lesion(s), then FNA 
untreated lesion is not required. 
s 
Quantitative results for anti-dsDNA are required. 
t 
All safety laboratory tests are to be performed at the local laboratory. 
u 
An extra aliquot of serum will be collected and stored frozen for possible future testing. 
v 
PET scans will only be permitted if PET/CT is the SOC at the participating institution. Perform a CT scan of neck, chest, abdomen, pelvis and other areas as clinically indicated at all imaging 
timepoints. The Day 180 CT scan can be done within 2 weeks prior to the subject receiving the first dose of localized radiation at the Day 180 visit only if the subject has consented to be treated 
with a second treatment cycle of localized low-dose radiation and SD-101.  
w 
The AE assessment at the ED Visit should occur 7 days or more after the subject’s last study injection. Subjects who are withdrawn due to a AE should have an AE assessment completed 28 days 
or more after the last study drug injection. If the subject is discontinuing study, the ED can be performed at the same visit as the AE assessment. 
x 
All concomitant medications taken by the subject from Screening through the end of the treatment period (Day 90 [Visit 9] for 1 cycle of SD-101 treatment or Day 270 [Visit18] for 2 cycles of 
SD-101 treatment) will be reported. Concomitant medications used to treat an SAE or immunomodulator drugs taken after Day 90 (Visit 9) for 1 cycle of treatment or after Day 270 (Visit 18) for 
2 cycles of treatment through Day 720 (Visit 13) or ED are also to be reported.


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 81 of 84 
APPENDIX 3: 
SCHEDULE OF STUDY ASSESSMENTS (PART 2 – SUBJECTS UNDERGOING 2 TREATMENT CYCLES) 
(CONT’D) 
FOOTNOTES (CONT’D) 
y  
Day 180 is the first day of localized low-dose XRT and Day 181 is the second day of localized low-dose XRT for subjects who have consented to receive Cycle 2 treatment of SD-101. Day 180 
and Day 181 XRT procedures should be completed before a subject receives Cycle 2 treatment of SD-101. The dose of SD-101 is the last dose level received in Part 2 Cycle 1. If a subject does 
not consent to be treated with localized low-dose radiation and SD-101 at Day 180, the subject will continue on the study and complete follow-up procedures outlined in Appendix 2. A lesion 
injected for Cycle 2 may be different than Cycle 1 but must meet size requirements per Inclusion Criterion #2. Do not change the label of lesions from Cycle 1 (ie, the lesion injected in Cycle 2 
may be Lesion A-G). The same lesion should be injected throughout a cycle. If the lesion regresses, then SD-101 should be injected in a peritumoral area.  
z 
Subject must meet eligibility criteria for laboratory assessments to receive Cycle 2 SD-101 treatment. 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 82 of 84 
APPENDIX 4: 
RESPONSE DEFINITIONS FOR CLINICAL TRIALS 
Response 
Definition 
Nodal Masses 
Spleen, Liver 
Bone Marrow 
CR 
Disappearance of all 
evidence of disease 
(a) FDG-avid or PET 
positive prior to therapy; 
mass of any size 
permitted if PET negative 
(b) Variably FDG-avid or 
PET negative; regression 
to normal size on CT 
Not palpable, nodules 
disappeared 
Infiltrate cleared on 
repeat biopsy; if 
indeterminate by 
morphology, 
immunohistochemistry 
should be negative 
PR 
Regression of 
measurable disease and 
no new sites 
≥ 50% decrease in SPD 
of up to 6 largest 
dominant masses; no 
increase in size of other 
nodes 
(a) FDG-avid or PET 
positive prior to therapy; 
1 or more PET-positive at 
previously involved site 
(b) Variably FDG-avid or 
PET negative; regression 
on CT 
≥ 50% decrease in SPD 
of nodules (for single 
nodule in greatest 
transverse diameter); no 
increase in size of liver 
or spleen 
Irrelevant if positive 
prior to therapy; cell 
type should be specified 
Stable 
Disease 
Failure to attain 
CR/PR or progressive 
disease 
(a) FDG-avid or PET 
positive prior to therapy; 
PET positive at prior sites 
of disease and no new 
sites on CT or PET 
(b) Variably FDG-avid or 
PET negative; no change 
in size of previous lesions 
on CT 
 
 
Relapsed 
disease or 
progressive 
disease 
Any new lesion or 
increase by ≥ 50% of 
previously involved 
sites from nadir 
Appearance of a new 
lesion(s) > 1.5 cm in any 
axis, ≥ 50% increase in 
SPD of > 1 node, or ≥ 
50% increase in longest 
diameter of a previously 
identified node > 1 cm in 
short axis 
Lesions PET-positive if 
FDG-avid lymphoma or 
PET positive prior to 
therapy 
> 50% increase from 
nadir in the SPD of any 
previous lesions 
New or recurrent 
involvement 
Source:  (Cheson, Pfistner et al. 2007). 
CR = complete response; CT = computed tomography; FDG = [18F] fluorodeoxyglucose; PET = Positive Emission Tomography; 
PR = partial response; SPD = sum of the products of the diameters. 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 83 of 84 
APPENDIX 5: 
ECOG PERFORMANCE STATUS INDEX 
The ECOG Performance Status is credited to the Eastern Cooperative Oncology Group, Robert 
Comis M.D., Group Chair. 
Status 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light housework, office work. 
2 
Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about 
more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead. 
Source:  (Oken, Creech et al. 1982). 
Available at:  http://www.ecog.org/general/perf_stat.html. Accessed 09 October 2015. 
 
 


Dynavax Technologies Corporation 
 
Protocol DV3-LYM-01 
SD-101 
 
Amendment #4 
 
CONFIDENTIAL AND PROPRIETARY 
Page 84 of 84 
APPENDIX 6: 
TOXICITY GRADING SCALE FOR HEALTHY ADULT AND 
ADOLESCENT VOLUNTEERS ENROLLED IN PREVENTIVE 
VACCINE CLINICAL TRIALS 
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with 
activity 
Any use of narcotic 
pain reliever or 
prevents daily activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant discomfort 
at rest 
ER visit or 
hospitalization 
Erythema/Rednessa 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or 
exfoliative dermatitis 
Induration/Swellingb 2.5 – 5 cm and does 
not interfere with 
activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or prevents 
daily activity 
Necrosis 
Source:  (Center for Biologics Evaluation and Research 2007). 
a         In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a 
continuous variable. 
b        Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
 

SAP_001.pdf: 
Sponsor: Dynavax Technologies
Protocol Identifier: DV3-LYM-01
Protocol Title: A Phase 1/2, Non-randomized, Open-label, Multicenter, Dose Escalation and 
Expansion Study of Intratumoral Injections of SD-101 in Combination With Localized Low-dose 
Radiation in Patients With Untreated Low-grade B-cell Lymphoma
Document: Statistical Analysis Plan
Document Date: 05 May 2017
NCT #: NCT02266147


Dynavax Technologies Corporation 
STATISTICAL ANALYSIS PLAN 
Study Title: 
A Phase 1/2, Non-randomized, Open-label, 
Multicenter, Dose Escalation and Expansion Study 
of Intratumoral Injections of SD-101 in 
Combination With Localized Low-dose Radiation 
in Patients With Untreated Low-grade B-cell 
Lymphoma 
Protocol Identifier: 
DV3-LYM-01 
Phase 
Phase 1/2 
Investigational Product: 
SD-101 
Indication: 
Low-grade B-cell Lymphoma 
Sponsor: 
Dynavax Technologies Corporation 
2929 Seventh Street, Suite 100  
Berkeley, CA 94710  
United States of America 
Reference Numbers: 
United States IND No.122809 
Original Version: 
Version 1 (26 June 2015) 
    Protocol Referenced: 
Amendment # 2 (10 April 2015) 
Current Version: 
Version 2 (05 May 2017) 
    Protocol Referenced: 
Amendment #4 (21 March 2016) 
CONFIDENTIAL
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Dynavax Technologies 
DVJ-LYM-01 
FINAL STATISTICAL ANALYSIS PLAN APPROVAL 
Prepared by: 
Approved by: 
Biao Xing, PhD 
Director, Biometrics 
Dynavax Technologies Corporation 
rftp~6tA~ 
Robert Janssen, MD 
Vice President Clinical Development 
and Regulatory Affairs 
and ChiefMedical Officer 
Dynavax Technologies Corporation 
Abraham Leung, MD 
Vice President Clinical Development 
Dynavax Technologies Corporation 
CONFIDENTIAL AND PROPRIETARY 
Date 
Date 
05 MAY 2017 
Page 2 of27 
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TABLE OF CONTENTS 
1.0 
INTRODUCTION..............................................................................................................6 
2.0 
STUDY OVERVIEW ........................................................................................................6 
3.0 
STUDY OBJECTIVES ......................................................................................................7 
3.1 
Primary Objectives...................................................................................................7 
3.2 
Secondary Objectives...............................................................................................7 
3.3 
Exploratory Objective ..............................................................................................7 
4.0 
ANALYSIS VARIABLES .................................................................................................7 
4.1 
Primary Endpoints ...................................................................................................7 
4.1.1 
Dose Limiting Toxicity ...........................................................................7 
4.1.2 
Incidence of Injection-Site Reactions .....................................................8 
4.1.3 
Changes in Interferon-Inducible Genes ..................................................8 
4.2 
Secondary Endpoints ...............................................................................................8 
4.3 
Exploratory Endpoints .............................................................................................9 
4.4 
Efficacy Variables ....................................................................................................9 
4.5 
Safety Variables .....................................................................................................10 
4.5.1 
Adverse Events......................................................................................10 
4.5.2 
Serious Adverse Events.........................................................................10 
4.5.3 
Laboratory Assessments........................................................................10 
4.5.4 
Vital Signs .............................................................................................11 
4.5.5 
Physical Examinations ..........................................................................11 
4.5.6 
Electrocardiograms ...............................................................................11 
4.6 
Pharmacokinetic/Pharmacodynamic Variables .....................................................11 
5.0 
SAMPLE SIZE CONSIDERATIONS ...........................................................................12 
6.0 
ANALYSIS POPULATIONS .........................................................................................12 
6.1 
Enrolled Population ...............................................................................................12 
6.2 
Safety Population ...................................................................................................12 
6.3 
Efficacy Population ................................................................................................13 
6.4 
Pharmacokinetic and Pharmacodynamic Population .............................................13 
7.0 
DEFINITIONS, COMPUTATIONS, AND CONVENTIONS ....................................13 
7.1 
Definitions and Computations ...............................................................................13 
7.2 
Conventions ...........................................................................................................14 
7.3 
Rules for Missing Data ..........................................................................................14 
8.0 
TIMING OF ANALYSES ...............................................................................................15 
9.0 
STATISTICAL METHODS ...........................................................................................15 
9.1 
Subject Disposition ................................................................................................16 
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9.2 
Protocol Deviations ................................................................................................16 
9.3 
Demographics and Baseline Characteristics ..........................................................16 
9.4 
Concomitant Medications ......................................................................................17 
9.5 
Medical History .....................................................................................................17 
9.6 
Analyses of Sepcified Endpoints ...........................................................................17 
9.6.1 
Primary Endpoints .................................................................................17 
9.6.1.1 
Dose Limiting Toxicities ...............................................................17 
9.6.1.2 
Incidence of Injection-Site Reactions ............................................17 
9.6.1.3 
Changes in IFN-Inducible Genes ...................................................17 
9.6.2 
Secondary Endpoints .............................................................................18 
9.6.2.1 
Plasma Concentrations of SD-101 .................................................18 
9.6.2.2 
Overall Response Rate and Response Rate of Treated 
Lesion(s) and Untreated Lesion(s) Respectively ...........................18 
9.6.2.3 
Time to Overall Response and Time to Response of 
Treated Lesion(s) and Untreated Lesion(s) Respectively ..............18 
9.6.3 
Exploratory Endpoints ..........................................................................18 
9.6.3.1 
Duration of Overall Response and Duration of Response of 
Treated Lesion(s), and Untreated Lesion(s) Respectively .............18 
9.6.3.2 
Time to Next Treatment .................................................................18 
9.6.3.3 
Time to Progression .......................................................................19 
9.6.3.4 
Other Exploratory Analyses ...........................................................19 
9.7 
Safety Analyses ......................................................................................................19 
9.7.1 
Adverse Events......................................................................................19 
9.7.2 
Laboratory Assessments........................................................................20 
9.7.3 
Vital Signs .............................................................................................20 
9.7.4 
Physical Examinations ..........................................................................20 
9.7.5 
Electrocardiograms ...............................................................................20 
9.8 
Analysis of Pharmacokinetics/Pharmacodynamics ...............................................21 
9.9 
Other Analyses .......................................................................................................21 
9.10 
Interim Analysis .....................................................................................................21 
9.11 
Reporting Output ...................................................................................................21 
10.0 
REVISION HISTORY ....................................................................................................22 
11.0 
REFERENCES .................................................................................................................22 
12.0 
LIST OF TABLES ...........................................................................................................23 
13.0 
LIST OF FIGURES .........................................................................................................25 
14.0 
LIST OF SUBJECT DATA LISTINGS .........................................................................26 
APPENDIX 1:  
RESPONSE DEFINITIONS FOR CLINICAL TRIALS ................27 
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List of Abbreviations and Terms 
Abbreviation 
Definition 
AE 
Adverse event 
AUC 
Area under the curve 
Cmax 
Maximum plasma concentration 
CR 
Complete response 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
Dose limiting toxicity 
ECG 
Electrocardiogram 
FNA 
Fine needle aspiration 
IFN 
Interferon  
MedDRA 
Medical Dictionary for Regulatory Activities 
MTD 
Maximum tolerated dose 
PBMC 
Peripheral blood mononuclear cells 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PR 
Partial response 
SAP 
Statistical analysis plan 
t1/2 
Terminal elimination half-life 
Tmax 
Time to maximum plasma concentration 
TEAE 
Treatment-emergent adverse event 
TTNT 
Time to next treatment 
TTP 
Time to progression 
WOCBP 
Women of child bearing potential 
XRT 
Radiation therapy 
 
 
 
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1.0 
INTRODUCTION 
This statistical analysis plan (SAP) contains definitions of analysis populations and 
endpoints, outlines the timing of statistical analyses, and provides a comprehensive 
description of statistical analyses to assess the pharmacokinetics (PK), pharmacodynamics 
(PD), preliminary efficacy, and safety of SD-101 as described in Protocol DV3-LYM-01 
(Amendment #4, 21 March 2016):  A Phase 1/2, Non-randomized, Open-label, Multicenter, 
Dose Escalation and Expansion Study of Intratumoral Injections of SD-101 in Combination 
With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell 
Lymphoma. 
2.0 
STUDY OVERVIEW 
This open-label, dose-ranging, multicenter study was designed to evaluate the safety and 
preliminary efficacy of localized low-dose radiation therapy (XRT) and intratumoral 
injection of SD-101 for the treatment of untreated low-grade B-cell lymphoma. The 
hypothesis to be tested in this study is that SD-101, by virtue of its potency and its ability to 
induce high levels of interferon-alpha (IFN-α), will generate antitumor immune responses 
when combined with XRT.  
IFNs have multiple effects on both the tumor cells and the tumor infiltrating leukocytes. 
IFNs can directly inhibit the proliferation of tumor cells and increase major 
histocompatibility complex class I expression, enhancing antigen recognition. Additionally 
IFNs have potent effects on tumor infiltrating leukocytes, including enhancing antigen 
presenting function of dendritic cells, increasing the effector function of T-cells, and 
activating cytotoxic activity of natural killer cells (Hervas-Stubbs, Perez-Gracia et al. 2011). 
The population to be studied will be subjects with untreated low-grade B-cell lymphomas 
who do not require immediate systemic therapy and are appropriate candidates for “watch 
and wait”.  
The study has 2 phases: Phase 1 (Dose Escalation) includes the evaluation of 4 levels of 
doses of SD-101 (1 mg, 2 mg, 4 mg, and 8 mg) that are tested sequentially using a 3+3 dose 
escalation study design; Phase 2 (Dose Expansion) includes the evaluation of approximately 
18 subjects (9 per cohort) into a 1 mg and 8 mg SD-101 dose cohort. 
Study treatment consists of local radiation over 2 days (2 Gy each day) followed by 5 weekly 
intratumoral injections of SD-101. Subjects enrolled in Phase 2 Expansion cohorts who 
achieve a response of at least stable disease according to Cheson critera for the untreated 
lesions on Day 180 will have an option to receive a second cycle of low dose radiation and 
SD-101 injections. Subjects will be followed for safety through Day 720 and for disease 
assessment per Cheson criteria until next treatment or until approximately 2 years after the 
first injection of SD-101.  
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3.0 
STUDY OBJECTIVES 
3.1 
Primary Objectives 
• To assess the safety and tolerability of escalating doses of SD-101 in combination with 
localized low-dose XRT in subjects with untreated low-grade B-cell lymphoma  
• To evaluate the PD profile of interferon (IFN)-inducible genes in whole blood 24 hours 
after intratumoral injection of SD-101  
• To determine the Maximum Tolerated Dose (MTD) or Optimal Dose of intratumoral 
SD-101 in combination with localized low-dose XRT  
3.2 
Secondary Objectives 
• To evaluate the plasma PK of SD-101  
• To assess the preliminary response both locally and systemically 
• Tumor shrinkage of the treated lesion(s), which is (are) lesion(s) treated with both 
XRT and SD-101 (Local) 
• Tumor shrinkage outside the treated lesion(s) (Systemic)  
3.3 
Exploratory Objective 
• To estimate the duration of tumor response both locally and systemically 
 
4.0 
ANALYSIS VARIABLES 
4.1 
Primary Endpoints 
4.1.1 
Dose Limiting Toxicity 
Dose limiting toxicity (DLT) is defined as any of the following AEs occurring from the time 
of the first injection (Day 1 [Visit 2]) through 7 days following the last injection (Day 36 
[Visit 8]): 
1) Any non-hematological toxicity ≥ Grade 3 except for alopecia or nausea controlled by 
medical management  
2) Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding or any 
requirement for platelet transfusion 
3) Febrile neutropenia of any duration (ANC < 1000/mm3, temperature ≥ 38.5°C)  
4)  Grade 4 neutropenia lasting more than 5 days 
5)  Grade 4 anemia unexplained by underlying disease 
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6) Any Grade 2 or higher toxicity related to SD-101 (eg, post-injection reaction or 
influenza-like illness) that does not resolve to Grade ≤ 1 with standard treatment by the 
time of the next treatment 
4.1.2 
Incidence of Injection-Site Reactions 
Injection-site reactions are defined as local AEs that occur following injection of SD-101. 
The study has specific procedures for collecting injection-site reactions that will be recorded 
as AEs in the study database. Local reactions (eg, redness, swelling, pain at or near the 
injection site) to intratumoral injections will be collected for 7 days following each injection. 
Local injection site reactions are considered AEs if they persist longer than 7 days. The 
severity of the local reactions will be graded using the Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (refer to 
Appendix 6 of protocol).  
All local reactions that occur will be captured, even if the diameter of the largest dimension 
does not meet a Grade 1 on the severity scale. As such, any reaction smaller than this size 
cannot be graded but will still be recorded in the clinical database, and the severity will be 
marked as not applicable (N/A).  
The subject will be provided with a Diary Card. Instructions will be provided to the subject 
on measuring and recording local injection-site reaction data (eg, redness, swelling, pain at or 
near injection site). Further, the Diary Card will solicit certain pre-defined AEs (eg, malaise, 
headache, chills, myalgia, fatigue, fever) and other health changes. All data documented by 
the subject on Diary Cards will be collected, reviewed by the study nurse/coordinator with 
the subject, and recorded on the appropriate CRF.  
4.1.3 
Changes in Interferon-Inducible Genes  
IFN-alpha inducible genes will be assayed by quantitative polymerase chain reaction (qPCR) 
of mRNA isolated from whole blood collected before administration of the first and second 
doses of SD-101 and after administration of the second dose of SD-101. 
The core group of genes measured will be ISG-54, Mx-B, IFN-alpha, TNF-alpha, IP-10, 
IRF-7, GBP-1, MCP-1, and MCP-2. Other genes may be tested to elucidate the patterns seen 
in the core genes. 
4.2 
Secondary Endpoints  
• Plasma concentrations of SD-101 
PK samples will be collected only in Phase 1 portion of the study at pre-dose and 1,2,4 
and 6 hours pose-dose on Day 1, and 24 hours post-dose on Day 9.   
• Overall response rate and response rate of  treated and untreated lesion(s), respectively 
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• Time to overall response and time to response of treated and untreated lesion(s), 
respectively 
 
4.3 
Exploratory Endpoints 
• Duration of overall response and duration of response of treated and untreated lesion(s), 
respectively  
• Time to next treatment (TTNT)  
• Time to progression (TTP) 
• Characterization of tumor infiltrating lymphocytes, co-stimulatory molecules, and other 
immune activated cells following SD-101 treatment 
 
4.4 
Efficacy Variables 
Response to treatment will be evaluated by the investigator at 3 and 6 months after the first 
study injection and then every 6 months for the remainder of the trial. 
Response as assessed by computerized tomography (CT)/positron emission tomography (PET) is 
in Appendix 1 (Cheson, Horning et al. 1999; Cheson, Pfistner et al. 2007). Response will be 
assessed on the basis of clinical, radiologic, and pathologic (ie, bone marrow) criteria. 
Response rate is defined as the proportion of subjects who achieved complete response (CR) 
or partial response (PR). Time to response is defined as time from first dose of SD-101 to 
time of initial response (CR, PR) for subjects who have response. For subjects who do not 
have response, time to response will be censored at the last tumor assessment before the end 
of follow up. For  subjects who have a response, duration of response will be measured from 
the date of initial response (CR, PR) to the date of progression for those who have disease 
progression. For those who do not have disease progression, duration of response will be 
censored by the date of last tumor assessment before the end of follow up or before initiation 
of subsequent therapy. 
Time to next treatment is defined as time from last dose of SD-101 to the time of next 
treatment for those who have next treatment (ie, non-protocol cancer treatment); for subjects 
who do not have next treatment, time to next treatment will be censored at the end of follow 
up. Time to progression is defined as the time from first dose of SD-101 to time of disease 
progression for those who have disease progression; for subjects who do not have disease 
progression, time to progression will be censored at the date of last tumor assessment before 
the end of follow up.  
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4.5 
Safety Variables 
4.5.1 
Adverse Events 
Non-serious AE collection will begin at the time of study drug administration and continue 
through Day 90 and, if treated in Cycle 2, from Day 180 until Day 270 or, for early 
discontinuation, 7 days or more after the last study injection. Additionally, per protocol 
section 10.11 - Subjects who are withdrawn due to an AE should have an AE assessment 
completed 28 days or more after their last study drug injection. Serious adverse event (SAE) 
collection and reporting will begin at the time the subject signs the informed consent and 
continue through the duration of trial participation. The severity of AEs will be assessed and 
confirmed by the investigator and will be graded using the CTCAE Version 4.03 grading 
scale (Table 11-1 of the protocol). For injection-site reactions, the severity will be assessed 
using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials (see Protocol Appendix 6). 
Screening/Predose Adverse Events 
AEs that started or worsened during the time of obtaining informed consent up to the first 
administration of study drug will be captured on the medical history case report form and in 
the subject’s clinical record.  
Treatment-Emergent Adverse Events 
Treatment-emergent adverse events (TEAEs) are AEs that started or worsened after 
administration of SD-101 and occurred during the protocol specified collection period. 
Treatment-Related Adverse Events 
Treatment-related TEAEs are defined as TEAEs assessed by investigators as possibly or 
probably related to study treatment. TEAEs with missing relationship to study treatment will 
be treated as treatment-related in the summary. 
4.5.2 
Serious Adverse Events  
An AE is considered an SAE if it meets any of the criteria stated in Section 11.4 of the 
protocol.  
4.5.3 
Laboratory Assessments 
Laboratory assessments are listed below and will be performed according to the Schedule of 
Study Assessments (Appendix 1-3 of protocol). Sample collections are to be done pre-
injection on treatment days.  
• Hepatitis and human immunodeficiency virus (HIV)- testing at Screening: hepatitis B 
surface antigen, anti-HBc, anti-HCV, and anti-HIV  
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• Chemistry: sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), Cr, 
glucose, calcium, AST, ALT, gamma glutamyl transpeptidase (GGT), LDH, bilirubin, 
alkaline phosphatase, and C-reactive protein (CRP)  
• Hematology: hemoglobin (Hgb), hematocrit, white blood cell count with differential, and 
platelet count 
• Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT)  
• For women of child bearing potential (WOCBP), serum pregnancy testing will be 
conducted at Screening and serum or urine pregnancy testing at subsequent visits as 
outlined in Appendix 1 of the protocol. Serum or urine pregnancy must be negative prior 
to study treatment. Dipstick can be used. All female subjects are considered to be 
WOCBP except if they have been post-menopausal for at least 2 years or surgically 
sterile for at least 1 year. 
• Reserve serum aliquot specimens will be collected and stored frozen for possible future 
testing.  
• Blood for antibodies to double-stranded DNA (anti-dsDNA) will be collected according 
to the Schedule of Study Assessments (Appendix 1-3 of protocol).  
• Additional details for specific tests are provided in the Laboratory Manual. 
4.5.4 
Vital Signs 
Vital signs will be recorded and will include measurements of heart rate, respiratory rate, and 
systolic and diastolic blood pressure. Vital signs taken at injection visits will include oral 
temperature. 
4.5.5 
Physical Examinations 
The investigator or qualified designee will conduct physical examinations. A complete 
physical examination will be conducted at Screening and early discontinuation (ED) visits, 
and a targeted physical examination (based on interval history and/or AEs) will be conducted 
at all other visits. 
4.5.6 
Electrocardiograms 
An electrocardiogram (ECG; 12-lead with standard parameters of heart rate, shape, size and 
duration of P wave, P-R interval, QRS, and T wave configuration) will be performed at 
Screening, after treatment on Day 15 (Visit 5), and on Day 36 (Visit 8). 
4.6 
Pharmacokinetic/Pharmacodynamic Variables 
For PK, changes from pre-second dose to 24 hours post-second dose of SD-101 will be 
summarized by dose groups. Maximum observed concentration (Cmax), time to reach Cmax 
(Tmax), half-life, and area under the concentration-time curve will be evaluated. 
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PD variables consist of IFN-alpha inducible genes, which will be assayed by quantitative 
polymerase chain reaction (qPCR) of mRNA isolated from whole blood collected before 
administration of the first and second doses of SD-101 and after administration of the second 
dose of SD-101. The core group of genes measured will be ISG-54, Mx-B, IFN-alpha, TNF-
alpha, IP-10, IRF-7, GBP-1, MCP-1, and MCP-2. Other genes may be tested to elucidate the 
patterns seen in the core genes.  
5.0 
SAMPLE SIZE CONSIDERATIONS 
This trial is designed to allow preliminary assessments of safety and biological activity in 
approximately 25 to 31 subjects. Approximately 13 subjects may be enrolled in the dose 
escalation part of the trial and approximately 12 to 18 subjects in the second part of the trial. 
The sample size of the dose escalation is based on a standard 3+3 design and 4 planned 
dosing cohorts (3 subjects for the first 3 cohorts and a potential of 6 subjects for the last 
cohort). The sample size for evaluation of response rate is based on the plan to pool all 
subjects treated at the MTD or optimal dose level which would include 3 escalation subjects 
and the expansion subjects (approximately 9 to 12 per dose level). For dose expansion, if the 
true response rate is 30%, a sample size of 12 subjects will have 74% chance to obtain 3 or 
more responders and 50% chance to obtain 4 or more responders. A 90% exact binomial 
confidence interval will be constructed as preliminary efficacy information for further 
investigation. The numbers of responses and probabilities of detecting a response if total 
population size for a cohort is 9 or 12 subjects is as below: 
 
 
Number of Responses 
Probabilities of Detecting Response 
Subjects Enrolled (N=9) 
Subjects Enrolled (N=12) 
≥ 1 
95% 
98% 
≥ 2 
80% 
91% 
≥ 3 
53% 
74% 
≥ 4 
27% 
50% 
≥ 5 
9% 
27% 
Subjects who do not complete at least 4 injections for reasons other than discontinuation for 
toxicity or who do not have an assessment of tumor response may be replaced. 
6.0 
ANALYSIS POPULATIONS 
6.1 
Enrolled Population 
The enrolled population is defined as all subjects who enrolled in the study.  
6.2 
Safety Population 
The safety population is defined as all subjects who receive at least one injection of study 
drug. The safety population will be used for all analyses of safety data.  
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6.3 
Efficacy Population 
The efficacy population is defined as all subjects who receive at least one injection of study 
drug and have at least one post-treatment tumor assessment. The efficacy population will be 
used for all analyses of efficacy data. In addition, efficacy analyses will be performed for the 
Enrolled Population, in which subjects who do not have post-baseline tumor assessment will 
be treated as non-responders.  
6.4 
Pharmacokinetic and Pharmacodynamic Population 
The PK population will consist of all enrolled subjects who receive the second dose of 
SD-101 and have measurable assessments at pre-dose through 24 hours post-dose for the 
second dose of SD-101 (Visit Days 8 and 9). 
The PD population will consist of all enrolled subjects who receive at least 1 dose of study 
drug and both screening and at least 1 post-enrollment assessment of the PD marker of 
analysis interest. 
7.0 
DEFINITIONS, COMPUTATIONS, AND CONVENTIONS 
7.1 
Definitions and Computations 
Study Day 
Study day will be calculated in reference to the date of first dose (Day 1). For assessments 
conducted on or after the first dose date, study day is calculated as (assessment date – first 
dose date + 1). For assessments conducted before the first dose date, study day is calculated 
as (assessment date – first dose date). There will be no Day 0.  
Date of First Dose and Date of Last Dose of Study Drug 
The date of the first dose of study drug is defined as the date a subject receives the first dose 
of the study drug. The date of the last dose of study drug is the date a subject receives the last 
dose of the study drug. 
Treatment-Emergent Period 
For AEs, the treatment-emergent period is defined as the duration of time from the date and 
time of the first dose of study drug administration through Day 90 and, if treated in Cycle 2, 
from Day 180 until Day 270 or, for early discontinuation, within 30 days after their last study 
injection.  
For SAEs, the treatment-emergent period is defined as the duration of time from the date and 
time of the first dose of study drug administration through the duration of trial participation. 
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Baseline Value and Post-baseline Value 
Unless otherwise specified, the baseline value is defined as the last measurement before the 
first administration (date and time) of study drug. Post-baseline value is defined as 
any measurement taken after the first administration of study drug. Change from baseline is 
defined as (post-baseline value – baseline value). Both date and time of study drug 
administration and measurement will be considered when calculating baseline value. If time 
is not available, then date only will be used.  
7.2 
Conventions 
Unless otherwise specified, the following conventions will be applied to all analyses: 
• 1 year = 365.25 days. Year is calculated as (days/365.25) rounded up to 1 significant 
digit. 
• 1 month = 30.4375 days. Month is calculated as (days/30.4375) rounded up to 
1 significant digit. 
• Age will be calculated by the following SAS code: age = floor(yrdif(birth_date, 
consent_date, 'AGE')) 
• 1 pound = 0.454 kg 
• 1 inch = 2.54 cm 
• Missing safety data will not be imputed unless otherwise specified. 
• For laboratory results collected as < or > a numeric value, 0.0000000001 will be 
subtracted or added, respectively, to the value. 
• For safety analyses, percentages will be calculated based on the number of subjects in the 
analysis population. 
• For by-visit observed data analyses, percentages will be calculated based on the number 
of subjects with non-missing data as the denominator unless otherwise specified. 
• For other continuous endpoints, the summary statistics will include mean, standard 
deviation, median, and minimum and maximum. 
• For categorical endpoints, the summary statistics will include counts and percentages. 
• AEs and medical history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) version 18.1. 
• Prior therapies and concomitant medications will be coded using the World Health 
Organization (WHO) Drug Dictionary Enhanced Format B2 (June 2015). 
7.3 
Rules for Missing Data 
In general, missing data will not be imputed.  
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However, imputation may be performed on partially or completely missing dates of the start 
and/or end dates of an AE in order to flag whether an AE was treatment-emergent or not. For 
AEs with a partial date, available date parts (year, month, and day) of the partial date will be 
compared with the corresponding date components of the start date and end date of the 
treatment-emergent period to determine if the event is treatment emergent. When in doubt, 
the AE will be considered treatment emergent by default. The following rules will be applied 
to impute partial dates for AEs: 
• If start date of an AE is completely or partially missing, impute as follows: 
• If both month and day are missing and year = year of treatment start date, then set to 
treatment start date. 
• If both month and day are missing and year ≠ year of treatment start date, then set to 
January 1. 
• If day is missing and month and year = month and year of treatment start date, then 
set to treatment start date. 
• If day is missing and month and year ≠ month and year of treatment start date, then 
set to first of the month. 
• If start date is completely missing and AE end date is on or after the treatment start 
date, set to treatment start date.  
• If start date is completely missing and AE end date is prior to the treatment start date, 
do not impute an AE start date. 
• If end date of an AE is partially missing, impute as follows: 
• If both month and day are missing, then set to December 31. 
• If only day is missing, then set to last day of the month. 
• If end date is completely missing, do not impute. 
Listings will show the original date information without imputation. 
8.0 
TIMING OF ANALYSES 
Final Statistical analysis will be performed at the end of the study. No interim analysis is 
planned for this study. 
9.0 
STATISTICAL METHODS 
Descriptive statistics, including the number of subjects (n), mean, standard deviation (SD), 
median, minimum, and maximum, will be used to summarize continuous variables. 
Categorical variables will be summarized by number (n) and percentage (%) of subjects in 
each category. All data processing, summarization, and analyses will be performed using 
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SAS Version 9.4 or higher. Specifications for tables, graphs, and data listings will be 
provided in the tables, figures, listings (TFL) specifications document.  
9.1 
Subject Disposition 
Subject disposition will be summarized by dose group for all subjects as follows:  Subjects 
screened, subjects treated, subjects who completed treatment as well as subject who 
discontinue treatment and the reasons for discontinuation (as documented on the case report 
form, including death, loss to follow-up, protocol violation, consent withdrawn to continue 
treatment, disease progression, AE, or other).  
A listing of subjects discontinuing the study after enrollment will be produced.  
9.2 
Protocol Deviations 
Subjects with major protocol deviations will be listed by dose group. Categories of major 
deviations include at least the following: 
• Eligibility criteria not met 
• Excluded concomitant medication taken 
• Incorrect dose received 
• Informed consent not signed before study-specific procedures were performed 
• Failing to complete at least 4 injections for reasons other than discontinuation for toxicity 
or subject withdrawal 
• Missing baseline disease assessment or do not have a post-baseline assessment of tumor 
response. 
A detailed list of all major protocol deviations will be determined before database lock and a 
listing of all major deviations will be provided.  
9.3 
Demographics and Baseline Characteristics 
Summary statistics for age, weight, height, and body mass index at baseline will be presented. 
Frequency tabulations for sex, race and ethnicity will be presented. Disease history will 
include disease type, stage, grade and prognostic scores if collected. These summaries will be 
presented by dose group for the all enrolled, safety, and efficacy populations if they are 
different.  
Listings will be provided for these parameters for all subjects.  
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9.4 
Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization 
(WHO) Drug Dictionary Enhanced (B2 format, June 2015). Prior medications are drugs and 
therapies used before the first dose date. Medications or therapies are considered concomitant 
if exposure occurs after the first dose date. The number and percentage of subjects with 
concomitant medications will be presented alphabetically by anatomical therapeutic chemical 
(ATC) class Level 2 and by decreasing order of frequency of preferred terms within each 
ATC class for the safety population. Subjects taking the same medication multiple times will 
be counted once per medication.  
All medications recorded on the case report form will be listed. 
9.5 
Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA Version 18.1).  
All medical history data will be provided in a listing.  
9.6 
Analyses of Sepcified Endpoints 
9.6.1 
Primary Endpoints  
9.6.1.1 
Dose Limiting Toxicities 
Incidence of DLTs will be tabulated by dose groups, and bar chart of incidence rates of DLT 
by dose groups will be generated. 
9.6.1.2 
Incidence of Injection-Site Reactions 
Incidence of local site reactions, AEs, and SAEs will be tabulated by maximum severity and 
dose for all dose groups. 
9.6.1.3 
Changes in IFN-Inducible Genes 
For each IFN-inducible gene, the fold increase from baseline will be summarized by dose 
groups. A line graph of the fold increase from baseline by dose groups will be generated. A 
composite score for IFN-inducible genes may be generated by calculating the geometric 
mean of subsets of gene scores relative to baseline for each subject followed by calculating 
the arithmetic mean of the geometric means within each cohort. The analyses will be 
performed by the Preclinical Research Group at Dynavax. The outputs as well as the 
summary report will be attached to the Clinical Study Report (CSR) as an appendix. 
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9.6.2 
Secondary Endpoints  
9.6.2.1 
Plasma Concentrations of SD-101  
For PK concentrations, changes from pre-second dose to 24 hours post-second dose of SD-
101 will be summarized by dose groups. Cmax, Tmax, half-life, and area under the 
concentration-time curve (AUC), if possible, will also be summarized by dose groups. 
Summaries of PK concentration by dose groups will also be presented graphically where 
possible. 
The analyses will be performed by the Preclinical Research Group at Dynavax. The outputs 
as well as the summary report will be attached to the CSR as an appendix. 
9.6.2.2 
Overall Response Rate and Response Rate of Treated Lesion(s) and 
Untreated Lesion(s) Respectively  
Overall response rate and response rate of treated lesion(s), untreated lesion(s) respectively 
will be analyzed descriptively and 90% exact binomial confidence interval will be calculated 
for each dose group.  
In addition, percent change from baseline over time as well as best percent change from 
baseline in treated lesion(s), untreated lesion(s) and all target lesions, respectively, will be 
plotted. 
9.6.2.3 
Time to Overall Response and Time to Response of Treated Lesion(s) and 
Untreated Lesion(s) Respectively 
Time to overall response and time to response of treated lesion(s) and untreated lesion(s) 
respectively will be summarized descriptively by dose groups.  
9.6.3 
Exploratory Endpoints  
 
9.6.3.1 
Duration of Overall Response and Duration of Response of Treated Lesion(s), 
and Untreated Lesion(s) Respectively  
For those subjects who achieved overall response or response on treated lesion(s) and 
untreated lesion(s), repectively, duration of response for each of these will be summarized by 
dose groups, and individual duration of response will be plotted. 
9.6.3.2 
Time to Next Treatment 
TTNT will be summarized by dose groups and Kaplan-Meier methods will be used to 
summarize time to next treatment; the 95% CI for the median will be provided.  
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9.6.3.3 
Time to Progression 
TTP will be summarized by dose groups and Kaplan-Meier methods will be used to 
summarize time to progression; the 95% CI for the median will be provided.  
9.6.3.4 
Other Exploratory Analyses 
Tumor infiltrating lymphocytes, co-stimulatory molecules, and other immune activated cells 
following SD-101 treatment may be summarized descriptively by dose group. 
9.7 
Safety Analyses 
All subjects in the safety population will be used in the safety analyses. Safety analyses will 
be summarized by dose group as treated. No formal statistical testing will be performed.  
The treatment-emergent period is defined in Section 7.1.  
9.7.1 
Adverse Events 
All AEs will be coded to preferred term and system organ class using MedDRA Version 
18.1.  
An AE that started or increased in severity during the treatment-emergent period (refer to 
Section 7.1of this document) will be considered a TEAE. A summary table will be provided 
for the overview of TEAEs. The number and percentage of subjects with TEAEs as classified 
by system organ class and preferred term, as well as the number and percentage of subjects 
with at least 1 TEAE, will be summarized by severity and dose group. Similar summaries 
will also be provided for TEAEs related to the study drug, TEAEs leading to study 
discontinuation, and serious TEAEs. Severity of TEAEs will be graded according to the 
National Cancer Institute Cancer Therapy and Evaluation Program Common Terminology 
Criteria for Adverse Events (CTCAE). A study treatment-related TEAE is defined as any 
TEAE with at least a possible relationship to the study drug as assessed by the investigator or 
that is missing the assessment of causal relationship whose relationship to the study drug 
could not be ruled out.  
Incidence of local site reactions, injection-site reaction AEs and SAEs will be tabulated by 
maximum severity and dose for all dose groups 
Subjects with multiple occurrences of events for a given preferred term, system organ class, 
or overall will only be counted once at the worst severity and strongest relationship to study 
drug for each preferred term, system organ class, and overall, respectively. TEAEs of 
unknown severity will be categorized separately. A TEAE of unknown relationship will be 
considered to be related to study drug.  
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Separate listings will be provided for all AEs, AEs leading to study drug discontinuation, 
serious SAEs, and fatal AEs.  
9.7.2 
Laboratory Assessments 
Laboratory data in this study consist of hematology, serum chemistry, coagulation, 
anti-dsDNA antibodies, and anti-SD-101 antibodies. Quantitative laboratory test results and 
their change from baseline will be summarized by scheduled visit. The last value before the 
first dose of study drug will be used as baseline.  
For anti-dsDNA and anti SD-101 antibody results, fold change from baseline will be 
summarized by dose group and scheduled visit. The analyses will be performed by the 
Preclinical Research Group at Dynavax. The outputs as well as the summary report will be 
attached to the CSR as an appendix. 
Laboratory data and shift analysis tables for hematology and serum chemistry tests will also 
be presented by CTCAE grade. Each laboratory result will be flagged as low (L), normal, or 
high (H) at each visit according to the laboratory reference ranges. 
All laboratory data will be provided in data listings.  
9.7.3 
Vital Signs 
Temperature, blood pressure (systolic and diastolic), and heart rate will be summarized 
at baseline and each subsequent scheduled assessment by dose groups as treated. Baseline 
results are defined as the last vital sign results taken before the date and time of the first dose 
of study drug. Change from baseline will be calculated and presented for each parameter at 
all scheduled post-baseline assessment time points.  
Vital sign data will be provided in a data listing.  
9.7.4 
Physical Examinations 
Individual physical examination data with abnormal findings flagged will be listed. 
9.7.5 
Electrocardiograms 
The numbers and percentages of subjects with categories of normal, not clinically significant 
abnormal, and clinically significant abnormal will be tabulated for the 12-lead ECG at 
scheduled visits. Shift tables showing changes from baseline to each scheduled visit and from 
baseline to the worst post-baseline measurement in overall ECG interpretation will be 
presented. The last value recorded before the first dose of study drug will be used as baseline. 
A summary table of 12-lead ECG parameters will be provided.  
ECG data will be provided in a data listing.  
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9.8 
Analysis of Pharmacokinetics/Pharmacodynamics 
For PK concentrations, changes from pre-second dose to 24 hours post-second dose of SD-
101 will be summarized by dose groups where possible. Cmax, Tmax, half-life, and area 
under the concentration-time curve will also be summarized. A graphical summary of PK 
concentrations will be generated where possible. 
PD parameters are part of the primary endpoints, and their analyses are described in the 
primary endpoints section of this analysis plan. 
These analyses will be performed by the Preclinical Research Group at Dynavax. The outputs 
as well as the summary report will be attached to the CSR as appendices. 
9.9 
Other Analyses 
No other analyses are planned.  
9.10 
Interim Analysis 
This is a Phase 1/2 dose-escalation trial. No interim analysis is planned for this protocol.  
9.11 
Reporting Output 
All outputs will be produced using SAS® version 9.4 or later.  
Post-text tables, listings, and statistical appendices will be produced as PDF and RTF files 
using output delivery system (ODS) and Times New Roman or a similar font size 9 or larger. 
Data will be presented in PDF and RTF tables with data in individual cells. Figures will be 
produced as PDF and RTF files using ODS and Times New Roman font.  
All tables, listings and statistical appendices will be produced to landscape. 
Tables and listings will be presented by dose group, if appropriate. 
Dose groups will be formatted as follows: 
• Phase I 
o 1 mg 
o 2 mg 
o 4 mg 
o 8 mg 
o Overall 
• Phase II 
o 1 mg 
o 8 mg 
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• Both Phases 
o 1 mg 
o 8 mg 
 
10.0 
REVISION HISTORY 
Version Date 
Author 
Comments/Rationale for Revision 
1.0 
26JUN2015 
Jason Chan 
New Document per Protocol Version 2 
2.0 
05MAY2017 
Biao Xing 
Amendment per Protocol Version 4 
 
 
11.0 
REFERENCES 
Cheson, B. D., S. J. Horning, B. Coiffier, M. A. Shipp, R. I. Fisher, J. M. Connors, T. A. 
Lister, J. Vose, A. Grillo-Lopez, A. Hagenbeek, F. Cabanillas, D. Klippensten, W. 
Hiddemann, R. Castellino, N. L. Harris, J. O. Armitage, W. Carter, R. Hoppe and G. P. 
Canellos (1999). "Report of an international workshop to standardize response criteria for 
non-Hodgkin's lymphomas. NCI Sponsored International Working Group." J Clin Oncol 
17(4): 1244. 
Cheson, B. D., B. Pfistner, M. E. Juweid, R. D. Gascoyne, L. Specht, S. J. Horning, B. 
Coiffier, R. I. Fisher, A. Hagenbeek, E. Zucca, S. T. Rosen, S. Stroobants, T. A. Lister, R. T. 
Hoppe, M. Dreyling, K. Tobinai, J. M. Vose, J. M. Connors, M. Federico and V. Diehl 
(2007). "Revised Response Criteria for Malignant Lymphoma." Journal of Clinical Oncology 
25(5): 579-586. 
Hervas-Stubbs, S., J. L. Perez-Gracia, A. Rouzaut, M. F. Sanmamed, A. Le Bon and I. 
Melero (2011). "Direct Effects of Type I Interferons on Cells of the Immune System." 
Clinical Cancer Research 17(9): 2619-2627. 
 
 
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12.0 
LIST OF TABLES 
Table 14.1.1 
Summary of Subject Disposition by Dose Group 
Table 14.1.2 
Summary of Important Protocol Deviations by Dose Group 
Table 14.1.3 
Summary of Anlaysis Populations by Dose Group 
Table 14.1.4 
Summary of Demographics and Baseline Characteristics by Dose Group 
Table 14.1.5 
Summary of Disease History by Dose Group 
Table 14.1.6 
Summary of Medical History Events by SOC, Preferred Term and Dose Group 
Table 14.1.7 
Summary of Prior Medications by ATC Level 2, Preferred Term and Dose 
Group 
Table 14.1.8 
Summary of Concomitant Medications by ATC Level 2, Preferred Term and 
Dose Group 
Table 14.2.1 
Summary of Treatment Exposure by Dose Group 
Table 14.3.1 
Summary of Response of Treated Lesion(s) by Dose Group 
Table 14.3.2 
Summary of Response of Untreated Lesion(s) by Dose Group 
Table 14.3.3 
Summary of Overall Response by Dose Group 
Table 14.3.4 
Summary of Response of Treated Lesion(s) by Dose Group and Disease Type 
Table 14.3.5 
Summary of Response of Untreated Lesion(s) by Dose Group and Disease 
Type 
Table 14.3.6 
Summary of Overall Response by Dose Group and Disease Type 
Table 14.3.7 
Time to Next Treatment by Dose Group 
Table 14.3.8 
Time to Disease Progression by Dose Group 
Table 14.4.1 
Overall Summary of Treatment-Emergent Adverse Events 
Table 14.4.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term and Dose Group 
Table 14.4.3 
Treatment-Emergent Adverse Events by Preferred Term and Dose Group 
Table 14.4.4 
 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, 
Severity and Dose Group  
Table 14.4.5 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, 
Severity and Dose Group for Grade 3 and Higher 
Table 14.4.6 
 
Treatment-Related Adverse Events by System Organ Class, Preferred Term, 
Severity and Dose Group 
Table 14.4.7 
Treatment-Emergent Serious Adverse Events by System Organ Class, 
Preferred Term and Dose Group 
Table 14.4.8 
 
Treatment-Related Serious Adverse Events by System Organ Class, Preferred 
Term and Dose Group 
Table 14.4.9 
Treatment-Emergent Adverse Events Leading to Dose Interruption of Study by 
System Organ Class, Preferred Term, Severity and Dose Group 
Table 14.4.10 
 
Treatment-Emergent Adverse Events Leading to Discontinuation of Study by 
System Organ Class, Preferred Term, Severity and Dose Group 
Table 14.4.11 
Treatment-Emergent Adverse Events Leading to Deaths by Dose Group 
Table 14.4.12 
Summary of Dose Limiting Toxicities by Dose Group 
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Table 14.4.13 
Summary of Injection Site Reactions By Dose Number, Dose Group and by 
Maximum Severity 
Table 14.4.14 
Summary of Deaths by Dose Group 
Table 14.5.1 
Summary of Observed Values and Change from Baseline by Dose Group:  
Hematology 
Table 14.5.2 
Shift Table of Hematology Parameters by Dose Group 
Table 14.5.3 
Summary of Observed Values and Change from Baseline by Dose Group:  
Chemistry 
Table 14.5.4 
Shift Table of Chemistry Parameters by Dose Group 
Table 14.5.5 
Summary of Observed Values and Change from Baseline by Dose Group:  
Coagulation 
Table 14.5.6 
Shift Table of Coagulation Parameters by Dose Group 
Table 14.6.1 
Summary of Vital Signs by Dose Group 
Table 14.6.2 
Summary of ECG by Dose Group 
Sub-Report 
Summary of Plasma Concentration of SD-101 by Dose Group 
Sub-Report 
Summary of Fold Change in Interferon-Inducible Genes Expression by Dose 
Group 
Sub-Report 
Summary of Observed Values and Change from Baseline of Antibodies to SD-
101 by Dose Group 
Sub-Report 
Summary of Observed Values and Change from Baseline of Antibodies to 
Double-Stranded DNA (anti-dsDNA) by Dose Group  
 
 
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13.0 
LIST OF FIGURES 
Figure 14.3.1.1 
Best Percent Change from Baseline in Treated Lesion(s) by Dose Group 
Figure 14.3.1.2 
Best Percent Change from Baseline in Treated Lesion(s) by Disease Type 
Figure 14.3.2.1 
Best Percent Change from Baseline in Untreated Lesion(s) by Dose Group 
Figure 14.3.2.2 
Best Percent Change from Baseline in Untreated Lesion(s) by Disease Type 
Figure 14.3.3.1 
Best Percent Change from Baseline in All Target Lesion(s) by Dose Group 
Figure 14.3.3.2 
Best Percent Change from Baseline in All Target Lesion(s) by Disease Type 
Figure 14.3.4.1 
Percent Change from Baseline Over Time in Treated Lesion(s) by Dose 
Group 
Figure 14.3.4.2 
Percent Change from Baseline Over Time in Treated Lesion(s) by Disease 
Type 
Figure 14.3.5.1 
Percent Change from Baseline Over Time in Untreated Lesion(s) by Dose 
Group 
Figure 14.3.5.2 
Percent Change from Baseline Over Time in Untreated Lesion(s) by 
Disease Type 
Figure 14.3.6.1 
Percent Change from Baseline Over Time in All Target Lesion(s) by Dose 
Group 
Figure 14.3.6.2 
Percent Change from Baseline Over Time in All Target Lesion(s) by 
Disease Type 
Figure 14.3.7.1 
Individual Response Status Over Time in Treated Lesion(s) by Dose Group 
Figure 14.3.7.2 
Individual Response Status Over Time in Treated Lesion(s) by Disease 
Type 
Figure 14.3.8.1 
Individual Response Status Over Time in Untreated Lesion(s) by Dose 
Group 
Figure 14.3.8.2 
Individual Response Status Over Time in Untreated Lesion(s) by Disease 
Type 
Figure 14.3.9.1 
Individual Response Status Over Time in All Target Lesion(s) by Dose 
Group 
Figure 14.3.9.2 
Individual Response Status Over Time in All Target Lesion(s) by Disease 
Type 
Figure 14.3.10.1 
Kaplan-Meier Plot of Time-to-Progression by Dose Group 
Figure 14.3.10.2 
Kaplan-Meier Plot of Time-to-Progression by Disease Type 
 
 
 
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14.0 
LIST OF SUBJECT DATA LISTINGS 
Listing 16.2.1.1 
Subject Disposition and Reasons for Discontinuation From Study  
Listing 16.2.1.2 
Analysis Populations and Reasons for Exclusion 
Listing 16.2.1.3 
Protocol Deviations 
Listing 16.2.2.1 
Demographics and Baseline Characteristics 
Listing 16.2.2.2 
Medical History 
Listing 16.2.2.3 
Disease History 
Listing 16.2.2.4 
Concomitant and Prior Medications 
Listing 16.2.3 
Study Drug Administration 
Listing 16.2.4.1 
Tumor Assessment 
Listing 16.2.4.2 
Disease Response Assessment 
Listing 16.2.5 
Next Treatment for B-cell Lymphoma 
Listing 16.2.6.1 
Adverse Events 
Listing 16.2.6.2 
Serious Adverse Events 
Listing 16.2.6.3 
Dose Limiting Toxicity 
Listing 16.2.6.4 
Injection-Site Reactions 
Listing 16.2.6.4 
Adverse Events Leading to Discontinuation of Study Treatment  
Listing 16.2.6.5 
Adverse Events Resulting in Death 
Listing 16.2.6.6 
Deaths 
Listing 16.2.7.1 
Hematology Results 
Listing 16.2.7.2 
Chemistry Results 
Listing 16.2.7.3 
Coagulation Results  
Listing 16.2.7.4 
Pregnancy Test Results  
Listing 16.2.8.1 
Vital Sign Results  
Listing 16.2.8.2 
Physical Examination Results 
Listing 16.2.8.3 
ECG Results 
Listing 16.2.9.1 
Bone Marrow Biopsy-Aspirate Results 
Listing 16.2.9.2 
Fine Needle Aspirate (FNA) Results 
Sub-Report 
Pharmacokinetic  Concentration 
Sub-Report  
Interferon Inducible Genes 
Sub-Report 
Antibodies to Double-Stranded DNA (anti-dsDNA) Results 
Sub-Report 
Antibodies to SD-101 Results 
 
 
 
CONFIDENTIAL
Page 26 of 27
16.1.9 Documentation of Statistical Methods and Interim Analysis Plans
SD-101
Dynavax Technologies Corporation
IND 122809/ SEQ No. 0037


Dynavax Technologies 
DV3-LYM-01 
05 MAY 2017 
CONFIDENTIAL AND PROPRIETARY 
Page 27 of 27 
APPENDIX 1: 
RESPONSE DEFINITIONS FOR CLINICAL TRIALS 
Response 
Definition 
Nodal Masses 
Spleen, Liver 
Bone Marrow 
CR 
Disappearance of all 
evidence of disease
(a) FDG-avid or PET
positive prior to therapy;
mass of any size
permitted if PET
negative
(b) Variably FDG-avid
or PET negative;
regression to normal size
on CT
Not palpable, nodules 
disappeared
Infiltrate cleared on 
repeat biopsy; if 
indeterminate by 
morphology, 
immunohistochemistry 
should be negative
PR 
Regression of 
measurable disease 
and no new sites
≥ 50% decrease in SPD 
of up to 6 largest 
dominant masses; no 
increase in size of other 
nodes
(a) FDG-avid or PET
positive prior to therapy;
1 or more PET-positive
at previously involved
site
(b) Variably FDG-avid
or PET negative;
regression on CT
≥ 50% decrease in SPD 
of nodules (for single 
nodule in greatest 
transverse diameter); 
no increase in size of 
liver or spleen
Irrelevant if positive 
prior to therapy; cell 
type should be 
specified
SD 
Failure to attain 
CR/PR or PD
(a) FDG-avid or PET
positive prior to therapy;
PET positive at prior
sites of disease and no
new sites on CT or PET
(b) Variably FDG-avid
or PET negative; no
change in size of
previous lesions on CT
Relapsed 
disease or 
PD
Any new lesion or 
increase by ≥ 50% of 
previously involved 
sites from nadir
Appearance of a new 
lesion(s) > 1.5 cm in any 
axis, ≥ 50% increase in 
SPD of > 1 node, or ≥ 
50% increase in longest 
diameter of a previously 
identified node > 1 cm 
in short axis
Lesions PET-positive if 
FDG-avid lymphoma or 
PET positive prior to 
therapy 
> 50% increase from
nadir in the SPD of any
previous lesions
New or recurrent 
involvement
Source:  (Cheson, Horning et al. 1999; Cheson, Pfistner et al. 2007). 
CR = complete remission; CT = computed tomography; FDG = [18F] fluorodeoxyglucose; PD = progressive disease; 
PET = positive emission tomography; PR = partial remission; SD = stable disease; SPD = sum of the product of the 
diameters. 
CONFIDENTIAL
Page 27 of 27
16.1.9 Documentation of Statistical Methods and Interim Analysis Plans
SD-101
Dynavax Technologies Corporation
IND 122809/ SEQ No. 0037