A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 With Pembrolizumab in Adults With Previously-Treated Malignant Pleural Mesothelioma
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Sponsor: Aduro Biotech, Inc.

  
 
CLINICAL STUDY PROTOCOL 
 
A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of  
CRS-207 with Pembrolizumab in Adults with Previously-Treated 
Malignant Pleural Mesothelioma 
 
Protocol Number:  
ADU-CL-13 
Version: 
 
 
2.0 
Date: 
 
 
14 June 2017  
Investigational Products: CRS-207 (live, attenuated, double-deleted 
Listeria monocytogenes encoding human 
mesothelin [Lm ∆actA/∆inlB hMeso]) 
 
Pembrolizumab (MK-3475) 
IND Number: 
 
13,389 
Sponsor:  
 
Aduro Biotech, Inc. 
740 Heinz Avenue 
Berkeley, CA 94710 USA 
Telephone: +1 510-848-4400 
 
 
 
 
Confidentiality Statement 
The information in this document is the confidential information of Aduro Biotech, Inc. Disclosure of this 
document is subject to an agreement between you or your institution and Aduro Biotech, Inc. When using 
this document: 
- Limit disclosure to the Institutional Review Board or Independent Ethics Committee and study 
personnel directly involved with conducting this protocol. 
- Inform the recipient of the confidential nature of this document and limit its use to the conduct of 
the study. 
- Direct any questions to Aduro Biotech, Inc. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
2 
2 
SYNOPSIS 
TITLE: A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 with 
Pembrolizumab in Adults with Previously-Treated Malignant Pleural Mesothelioma 
PROTOCOL NUMBER: ADU-CL-13 
INVESTIGATIONAL PRODUCTS:  
CRS-207 (live, attenuated, double-deleted Listeria monocytogenes encoding human mesothelin 
[Lm ΔactA/ΔinlB hMeso])  
Pembrolizumab (MK-3475, Merck, 2014) 
PHASE: 2 
SITES: Up to 12 sites 
INDICATION(S): Treatment of patients with malignant pleural mesothelioma (MPM) with 
disease progression following prior systemic chemotherapy 
OBJECTIVES: 
• Assess safety and tolerability of CRS-207 and pembrolizumab 
• Evaluate the effect of CRS-207 and pembrolizumab on tumor response, pulmonary function, 
and survival 
• Characterize the immune response following administration of CRS-207 and pembrolizumab 
STUDY DESIGN: 
ADU-CL-13 is a single-arm, open-label, multicenter Phase 2 study to evaluate the safety and 
efficacy of CRS-207 administered with pembrolizumab. The population for this study will 
consist of approximately 35 adults with histologically-confirmed MPM (epithelial or biphasic) 
whose disease has progressed after prior systemic chemotherapy. The study will consist of a 
Screening Period, Treatment Period (including a Safety Run-in), and a Follow-up Period.  
A schematic of the study design is provided below. 
 
 
  
 
 
 
 
ECOG = Eastern Cooperative Oncology Group; MPM = malignant pleural mesothelioma; QxW = every x weeks 
CRS-207 and pembrolizumab will be administered in 3-week cycles.  For Cycle 1, 
pembrolizumab (200 mg) will be administered by intravenous infusion (IV) over 30 minutes on 
Day 1 and CRS-207 (starting dose 1 × 109 colony-forming units [CFU]) will be administered IV 
 
Pembrolizumab 
(Q3W) 
CRS-207  
( Cycle 1 -4, Q3W ; 
after Cycle, Q6W)  
Patients with
MPM with
1-2 prior
treatment  
ECOG 0 or 1
N=35 
Treatment Period 
Follow -up 
every 12 weeks 
for survival & 
subsequent 
treatment

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
3 
over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 will be 
administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will 
continue to be administered on Day 1 at each treatment cycle (every 3 weeks; Q3W); CRS-207 
will be administered once every 6 weeks (i.e. every other treatment cycle; Q6W).  Alternatively, 
study drug administration may revert back to consecutive day-dosing regimen as performed in 
Cycle 1 (Day 1 pembrolizumab and Day 2 CRS-207). 
Treatment cycles with pembrolizumab will continue for up to 35 cycles as long as there is 
adequate safety and potential for clinical benefit. After cycle 35, subjects may receive CRS-207 
monotherapy if subject meets dosing eligibility, is clinically stable, and the subject is deriving 
clinical benefit.  If radiographic disease progression is observed, clinically stable subjects who 
meet dosing eligibility may continue to receive CRS-207 and pembrolizumab at the discretion of 
the Investigator. Subjects who experience unacceptable toxicity(ies) related to either CRS-207 or 
pembrolizumab may continue on study and receive CRS-207 or pembrolizumab monotherapy 
with approval from medical monitor. Subjects who experience unacceptable toxicity(ies) related 
to both CRS-207 and pembrolizumab in Cycle 1 should be discontinued from the treatment.  
However, if in the opinion of the investigator, the subject is deriving clinical benefit from the 
study treatment, the subject may be allowed to continue with treatment after discussion with the 
Medical Monitor.   
A Safety Run-in will be completed since there are no precedent data on the use of 
pembrolizumab with CRS-207. Treatment of the first 6 subjects will be staggered, with no more 
than 1 subject treated per week; subjects will be monitored for unacceptable toxicity(ies) during 
the first 28 days (at least through 7 days after the Cycle 2 dose). During the Safety Run-in, 
evaluable subjects are defined as those who remain on study for the 28-day monitoring period, 
subjects with unacceptable toxicity, and subjects who are discontinued for safety reasons at the 
Investigator’s discretion (even if criteria for unacceptable criteria are not met). The medical 
monitor and participating investigators will review all unacceptable toxicities on an ongoing 
basis and determine if the Safety Review Team should meet ad hoc to evaluate further.  In the 
event 2 subjects in the first 6 treated experience unacceptable toxicity(ies), the Safety Review 
Team will be convened to determine if the dose of CRS-207 will be reduced in subsequently 
enrolled subjects in half-log increments.   
Safety data including all unacceptable toxicities will be reviewed by a Safety Review Team 
comprised of participating investigators in the study, the Medical Monitor, and representatives 
of the Sponsor. Once the Safety Run-in period is complete, safety will continue to be evaluated 
on an ongoing basis in this open-label study. Cumulative clinical experience with CRS-207 and 
pembrolizumab will be used to assess whether adverse events (AEs) are considered expected.  If 
>33% of subjects dosed experience unacceptable toxicity(ies) attributable to study drug(s), the 
Safety Review Team will be convened to determine if dosing will be suspended. The schedule of 
events is provided in Table 2-1 or Table 2-2 for subjects who experience tolerability issues and 
continue to follow the consecutive-day dosing regimen). Tumor imaging and pulmonary 
function will be assessed at baseline (Screening) and during the Treatment Period approximately 
every 6 weeks starting at Cycle 3. Tumor measurement and assignment of response will be 
determined by local Investigators using the modified response evaluation criteria in solid tumors 
(modified RECIST) for MPM (Byrne, 2004). If radiographic disease progression is observed, 
another scan should be done at least four weeks later to confirm disease progression prior to 
treatment discontinuation. Peripheral blood will be collected to assess immune responses 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
4 
directed against L. monocytogenes, mesothelin, and other tumor-associated antigens. Paired 
tumor biopsies will be collected at Screening and during Cycle 2 to explore the association of 
programmed death receptor ligand-1 (PD-L1) expression and tumor-infiltrating lymphocyte 
characteristics with clinical responses. Blood will be collected at End of Treatment (EOT) to 
assess clearance of CRS-207 and at 
 
The Treatment Period is defined as the time from the first dose of study drug administration until 
discontinuation of both CRS-207 and pembrolizumab and completion of an End of Treatment 
(EOT) visit. All subjects must complete an End of Treatment (EOT) visit no more than four 
weeks following the final dose of study drug and/or prior to receipt of other cancer-related 
treatment. Subjects will be administered antibiotics beginning at the EOT visit to eliminate any 
potentially residual CRS-207.  At the end of the Treatment Period, subjects will enter the 
Follow-up Period of the study and will be followed for survival and subsequent cancer-related 
therapies every 3 months until death or close of study by the Sponsor. Sites will attempt to 
obtain vital status data from public records or other external sources where possible if a subject 
withdraws consent from study (i.e. refuse follow-up for vital status) or is documented as lost to 
follow up. 
INCLUSION AND EXCLUSION CRITERIA: 
Inclusion Criteria 
Individuals eligible to participate in this study must meet all of the following criteria: 
1. Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a 
predominantly (≥50%) epithelial component  
2. No more than 2 prior lines of anti-cancer therapy, one of which must have included 
pemetrexed and a platinum. Documented radiographic progression of disease after treatment 
with pemetrexed and a platinum is required. 
3. Measurable disease as defined by modified RECIST for MPM 
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 
5. Adequate organ and marrow function at Screening, as defined by: 
• White blood cell count ≥ 3000/ µL 
• Absolute neutrophil count ≥ 1500/µL 
• Absolute lymphocyte count ≥ 800/µL 
• Platelet count ≥ 100,000/µL 
• Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), or ≤ 3 × institutional ULN if 
due to Gilbert’s disease 
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × 
institutional ULN or ≤ 5 × ULN for subjects with liver metastases 
• Albumin ≥ 3.0 g/dL 
• Serum creatinine ≤1.5 × institutional ULN 
• Hemoglobin ≥ 9.0 g/dL 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
5 
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN and activated 
partial thromboplastin time (aPTT) ≤1.5 × ULN (if receiving anticoagulant therapy, 
values should be within therapeutic range of intended use) 
Any Grade 3 or higher abnormality in any serum chemistry or hematology parameter must 
be discussed and approved by the Medical Monitor prior to enrollment (even if considered 
not clinically significant) 
6. Aged 18 years and over 
7. Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of 
predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air as 
measured by pulse oximeter 
8. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must 
use highly effective contraception [per (CTFG, 2014)] throughout the Treatment Period 
(from first dose and through 120 days after final dose of study drug). Contraception must 
include at least one barrier method to minimize risk of fluid transmission. 
9. Provide written informed consent and is willing and able to comply with all study 
procedures. 
Exclusion Criteria 
Individuals who meet any of the following exclusion criteria will not be eligible to participate in 
the study: 
1. Pleurodesis within 14 days prior to first dose of study drug 
2. Has a diagnosis of immunodeficiency, receiving TNF pathway inhibitors, PI3 kinase 
inhibitors, chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone 
equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first 
dose of study drug 
3. Active second malignancy with the exception of any of the following: 
• Adequately treated basal cell carcinoma  
• Squamous cell carcinoma of the skin, or in situ cervical cancer 
• Low-risk prostate cancer (i.e. Gleason score < 7 and prostate specific antigen < 10 
ng/mL); or 
• Any other cancer from which the individual has been disease-free for ≥ 3 years 
4. Untreated or unstable brain metastases. Individuals with treated (surgically excised or 
irradiated) and stable brain metastases are eligible as long as the subject has adequately 
recovered from treatment and the treatment was ≥ 28 days prior to first dose of study drug. A 
baseline brain computed tomography (CT) with contrast or magnetic resonance imaging 
(MRI) within 14 days prior to first dose of study drug must be negative for new brain 
metastases. 
5. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not 
recovered from adverse effects due to agents administered more than 4 weeks earlier 
6. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
6 
prior to first dose of study drug 
7. Ongoing adverse effects (i.e. ≤ Grade 1 or at baseline) due to a previously administered anti-
cancer agent. Individuals with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception 
to this criterion. 
8. History of (non-infectious) pneumonitis that required steroids or current pneumonitis 
9. History of interstitial lung disease  
10. Received transfusion of blood products (including platelets or red blood cells) or 
administration of colony-stimulating factors (including G-CSF, GM-CSF or recombinant 
erythropoetin) within 4 weeks prior to first dose of study drug 
11. Active infection requiring systemic therapy 
12. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other 
checkpoint pathways (e.g. CTLA-4) 
13. Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer 
vaccine, or adoptive T cell immunotherapy 
14. Received any prophylactic vaccine within 14 days of first dose of study drug or received a 
live vaccine within 30 days of planned start of study therapy.  Seasonal flu vaccines that do 
not contain live virus are permitted. 
15. Participated in any other study in which receipt of an investigational new drug, or 
investigational device occurred within 28 days of first dose of study drug 
16. Clinically significant heart disease (such as uncontrolled angina, myocardial infarction 
within 3 months of study initiation, congestive heart failure, or New York Heart Association 
Class III or IV heart failure) 
17. Known valvular heart disease that requires antibiotic prophylaxis for prevention of 
endocarditis 
18. Known allergy to both penicillin and sulfa drugs 
19. Known or suspected allergy or hypersensitivity to yeast or any other component of CRS-207 
(e.g. glycerol) or pembrolizumab; or history of severe hypersensitivity (≥ Grade 3) to 
pembrolizumab and/or any of its excipients. 
20. History of autoimmune disease that has required systemic treatment in the past 2 years, 
including:  
• Inflammatory bowel disease (including ulcerative colitis and Crohn’s Disease) 
• Rheumatoid arthritis 
• Systemic progressive sclerosis (scleroderma) 
• Systemic lupus erythematosus 
• Autoimmune vasculitis (e.g. Wegener’s granulomatosis) 
• Central nervous system or motor neuropathy considered of autoimmune origin (e.g. 
Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis) 
Individuals with vitiligo, moderate to severe psoriasis, Sjogren’s Syndrome, interstitial 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
7 
cystitis, Graves’ or Hashimoto’s Disease, celiac disease, diabetes mellitus type 1, or 
hypothyroidism stable on hormone replacement may be allowed with Medical Monitor 
approval. 
21. Received a diagnosis of human immunodeficiency virus (HIV) 
22. Received a diagnosis of hepatitis B, or hepatitis C for which there is no clear evidence of 
natural immunity, immunity subsequent to vaccination, or successful eradication of the virus 
following antiviral therapy (individuals who are hepatitis C antibody positive may be 
enrolled if negative viral load confirmed at Screening) 
23. If WOCBP, pregnant or breastfeeding; negative pregnancy status must be confirmed within 
24 hours of first dose of study drug. 
24. Implanted medical devices that pose high risks for colonization and cannot be easily 
removed (e.g., artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), 
metal plate(s)) if infection occurs. Other common devices such as venous access devices 
(e.g., Port-a-Cath or Mediport) may be permitted as well as arterial and venous stents and 
dental and breast implants that were placed more than 3 months prior to first dose of study 
drug. 
25. Major surgery or significant traumatic injury occurring within 28 days prior to first dose of 
study drug. If major surgery occurred > 28 days prior to first dose of study drug, individual 
must have recovered adequately from the toxicity and/or complications from the intervention 
prior to the first dose of study drug. 
26. Unhealed wound or ulcer; or a bone fracture considered non-healing 
27. History or evidence of inherited bleeding diathesis or coagulopathy 
28. Unable or unwilling to withhold or discontinue any prohibited or restricted 
medications/procedures for the specified periods during the study 
29. Intercurrent illness that is either life-threatening or of clinical significance such that it might 
limit compliance with study requirements, or in the Investigator’s assessment would place 
the subject at an unacceptable risk for study participation. 
DURATION OF SUBJECT PARTICIPATION: 
The Screening Period may last up to 28 days. During the Treatment Period, a subject may 
continue to receive study drugs after documented progression provided dosing eligibility criteria 
are satisfied, and the investigator thinks the subject may be benefitting from continued 
treatment. Pembrolizumab may be administered up to a maximum of 35 cycles.  After cycle 35, 
subjects may receive CRS-207 monotherapy if subject meets dosing eligibility, is clinically 
stable, and the subject is deriving clinical benefit.  Discontinuation may occur due to unexpected 
clinical significant adverse event, lack of clinical benefit as determined by the investigator, 
withdrawal of consent by the subject, or termination of the study by the Sponsor. At the end of 
the Treatment Period, subjects will enter the Follow-up Period and will be followed for survival 
and subsequent cancer-related therapy every 3 months until death or close of study by the 
Sponsor.  
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
8 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
CRS-207 is formulated as 1 × 109 CFU suspended in 
 
, filled into a single-use 2-mL glass vial with a gray butyl stopper and 
aluminum crimp seal with a flip off cap. 1.0 mL of CRS-207 is diluted in sterile saline and 
administered by IV infusion over approximately 1 hour.  
Pembrolizumab for injection is a sterile, preservative-free, clear to slightly opalescent, colorless 
to slightly yellow solution. Each vial contains 100 mg/4 mL (25 mg/mL) solution in a single-use 
vial. Each 1 mL of solution contains 25 mg of pembrolizumab formulated in L-histidine (1.55 
mg), polysorbate 80 (0.2 mg), sucrose (70 mg), and Water for Injection, USP. Pembrolizumab 
will be diluted in sterile saline and administered at a dose of 200 mg via IV infusion over 30 
minutes. 
EFFICACY VARIABLES:  
Tumor measurements will be performed by radiologic evaluation (CT). All tumor response 
variables will be assessed by the Investigator using modified RECIST for MPM. Pulmonary 
function will be assessed by spirometry. 
Primary Efficacy Variable: 
• Objective response rate (ORR), defined as the proportion of subjects with complete response 
(CR) or partial response (PR)  
Secondary Efficacy Variables: 
• Disease control rate (DCR), defined as the percentage of subjects with CR, PR, or stable 
disease (SD) 
• Progression-free survival (PFS) defined as time from first dose of study drug until disease 
progression or death 
• Proportion of subjects with improvement in pulmonary function (FVC), defined as an 
increase from baseline of either ≥400 mL or ≥20% assessed using spirometry  
• Overall survival (OS), as measured from date of first dose of study drug until death 
SAFETY VARIABLES: 
Safety will be assessed by collection of data on AEs, clinical laboratory assessments, ECOG 
performance status, vital signs, weight, physical examination, electrocardiogram (ECG) 
parameters, concomitant medications, and testing blood for CRS-207 clearance. 
STATISTICAL ANALYSES: 
Descriptive summaries for categorical variables will include counts and percentages. Descriptive 
summaries for continuous variables will include means, medians, standard deviations and 
minimum and maximum values. Descriptive summaries of time to event data will include 
medians and confidence intervals. Graphical summaries of the data may be presented. All data 
will be listed for all subjects. Further details of the analysis, including the handling of missing 
data, transformations, other data handling procedures, and analytical methodology will be 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
9 
provided in the Statistical Analysis Plan (SAP). Exploratory analyses of the data will be 
conducted as deemed appropriate. 
All analyses of efficacy and safety will be performed on all subjects who were enrolled and 
received at least one dose of study drug. 
Efficacy Analyses 
For the primary efficacy analysis, ORR is defined as the proportion of subjects with PR or CR 
according to modified RECIST for MPM. Subjects who discontinue due to toxicity or clinical 
progression prior to post-baseline tumor assessments will be considered as non-responders. 
Subjects who discontinue for other reasons prior to post-baseline tumor assessments will be 
replaced and will not be included in the primary efficacy analysis. 
Secondary efficacy variables will be calculated for all subjects who receive at least one dose of 
study drug and are evaluable for response. 
The primary definition for objective disease response and disease progression will be determined 
by the Investigator using modified RECIST for MPM. Additional supportive analyses may be 
performed separately by an independent reviewer using objective disease responses definitions 
based on RECIST v1.1 and/or immune related response criteria (irRC). 
Safety Analyses 
AEs will be coded according to MedDRA version 18.1 or higher and assessed for severity using 
the NCI-CTCAE v. 4.03. AEs will be summarized by system organ class and preferred term and 
presented in decreasing order of frequency. 
Changes in vital signs, ECG data, hematology, serum chemistry, and urinalysis parameters from 
baseline to the EOT will be examined. Treatment-emergent changes from normal to abnormal 
values in key laboratory parameters will be identified. Laboratory data will be summarized for 
each time-point that specimens are collected. Changes in NCI toxicity grading will be presented 
using shift tables and listings of clinically significant values. 
SAMPLE SIZE DETERMINATION: 
The sample size is based on an A’Hern single-stage phase 2 design (A'Hern, 2001). A sample 
size of 35 evaluable subjects are required to decide whether the proportion responding is less 
than or equal to 0.21 or greater than or equal to 0.40. If the number of responses is 12 or more, 
the hypothesis that P ≤ 0.21 is rejected with a target error rate of 0.05 (alpha). If the number of 
responses is 11 or less, the hypothesis that P ≥ 0.40 is rejected with a target error rate of 0.20 
(power = 0.80). 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
10 
 Table 2-1  Schedule of Events: Same-day (D1) Dosing Regimen1 
 
 
 
 
Screen 
 
Treatment Period 
EOT3 
Follow-
up 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycles 5 and Beyond 
Within 4 
Weeks Post 
Final Dose 
 
 
Odd 
Numbered 
Cycles 
(5, 7, etc.) 
Even 
Numbered 
Cycles 
(6, 8, etc.) 
Study Day2 
-28 to 0 
1 
2 
3 
9 
1 
2 
8 
15 
1 
2 
8 
1 
2 
1 
1 
- 
- 
Visit Window (Days) 
- 
-3 
- 
- 
±1 
±3 
- 
±1 
±1 
±3 
- 
±1 
±3 
- 
±3 
±3 
-3 
±7 
Study Procedures 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion; 
Enrollment Form4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and Medication 
History, Height5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biopsy6 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Archived Tumor Tissue7 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT Tumor Evaluation8 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
Pulmonary Function Test9 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
Electrocardiogram,  
12-lead10 
X 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
ECOG Performance Status 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
X 
 
Physical Examination and 
Weight11 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
X 
 
Vital Signs12 
X 
X 
X 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
 
Pulse Oximetry12 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
X 
 
Adverse Event 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X13 
X 
 
Concomitant Medication 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X13 
X 
 
Survival Follow-up 
Contact14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Laboratory Sample Collection15                  Central lines must not be accessed for blood collection or for any reason during or within 4 days of CRS-207 infusion 
Virology Screen
16 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology and 
Chemistry17 
X 
X 
X 
X 
 
X 
X 
 
 
X 
X 
 
X 
X 
X 
X 
X 
 
Coagulation Panel18 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
Urinalysis19 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
X 
 
Thyroid Function Test20 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
 
X 
 
Pregnancy Test21 
X 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
11 
 
 
 
 
Screen 
 
Treatment Period 
EOT3 
Follow-
up 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycles 5 and Beyond 
Within 4 
Weeks Post 
Final Dose 
 
 
Odd 
Numbered 
Cycles 
(5, 7, etc.) 
Even 
Numbered 
Cycles 
(6, 8, etc.) 
Study Day2 
-28 to 0 
1 
2 
3 
9 
1 
2 
8 
15 
1 
2 
8 
1 
2 
1 
1 
- 
- 
Visit Window (Days) 
- 
-3 
- 
- 
±1 
±3 
- 
±1 
±1 
±3 
- 
±1 
±3 
- 
±3 
±3 
-3 
±7 
Research Sample Collection                                      Central lines must not be accessed for blood collection or for any reason during or within 4 days of CRS-207 infusion 
CD4 and CD8 Counts22  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA typing22 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum/Plasma for Immune 
Monitoring23 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Whole Blood for PBMC24 
 
X 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
 
X 
 
Blood for CRS-207 
Surveillance25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Study Medication 
Pembrolizumab1, 13, 26 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
 
 
CRS-2071, 13, 27, 28 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
Antibiotics (with diary)29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Subset Studies (select sites only) 
CRS-207 
Clearance/Shedding 
 
 
X30 
X30 
 
 
 
 
 
 
 
 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
12 
Table 2-2: Schedule of Events: Consecutive-day (Day 1 and 2) Dosing Regimen (for Subjects with Tolerability Issues)1 
 
Treatment Period 
EOT3 
Follow-up 
Cycle 2 
Cycle 3 
Cycle 4 
Cycles 5 and Beyond 
Within 4 
Weeks 
Post 
Final 
Dose 
 
 
Odd 
Numbered 
Cycles 
(5, 7, etc.) 
Even 
Numbered 
Cycles 
(6, 8, etc.) 
Study Day2 
1 
2 
3 
9 
15 
1 
2 
3 
9 
1 
2 
3 
9 
1 
1 
2 
- 
- 
Visit Window (Days) 
±3 
- 
- 
±1 
 
±3 
- 
- 
±1 
±3 
- 
- 
±1 
±3 
±3 
- 
-3 
±7 
Study Procedures 
Biopsy6 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT Tumor Evaluation8 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Pulmonary Function Test9 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Electrocardiogram, 12-lead10 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
ECOG Performance Status 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
Physical Examination and Weight11 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
Vital Signs12 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
Pulse Oximetry12 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
Adverse Event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X 
X13 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X13 
X 
X13 
X 
 
Survival Follow-up Contact14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Laboratory Sample Collection15                  Central lines must not be accessed for blood collection or for any reason during or within 4 days of CRS-207 infusion 
Hematology and Chemistry17 
X 
X 
X 
 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
Coagulation Panel18 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urinalysis19 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
Thyroid Function Test20 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Pregnancy Test21 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
Research Sample Collection                                      Central lines must not be accessed for blood collection or for any reason during or within 4 days of CRS-207 infusion 
Serum/Plasma for Immune 
Monitoring23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
X 
 
Whole Blood for PBMC24 
X 
 
 
X 
X 
 
 
X 
X 
 
 
 
X 
 
 
X 
 
Blood for CRS-207 
Surveillance25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Study Medication 
Pembrolizumab1, 13, 26 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
CRS-2071, 13, 27, 28 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
Antibiotics (with diary)29 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Subset Studies (select sites only) 
CRS-207 Clearance/Shedding30 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
13 
 
FOOTNOTES FOR TABLE 2-1 AND TABLE 2-2 
1 
CRS-207 and pembrolizumab will be administered in 3-week cycles.  For Cycle 1, pembrolizumab will be administered on Day 1 and CRS-207 on Day 2. If the 
infusions are well tolerated, pembrolizumab and CRS-207 may be administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab 
will continue to be administered on Day 1 at each treatment cycle every 3 weeks; CRS-207 will be administered once every 6 weeks. If there is intolerance to 
same day dosing, study drug administration may revert back to consecutive day-dosing regimen as performed in Cycle 1 during the Safety Run-in Period (Table 
2-2). Treatment cycles with pembrolizumab will continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit.   
2 
At visits where dosing is indicated, all assessments should be completed prior to dosing unless stated otherwise. If any doses are delayed, adjust subsequent 
dosing schedule accordingly. 
3 
EOT Visit will occur within 4 weeks after the final dose of study drug or prior to start of subsequent cancer-related therapy. If the EOT visit occurs earlier than 4 
weeks, a safety follow-up contact on Day 28 (-3 days) is required to complete the AE reporting period; document contact in the study records.  After the EOT 
Visit, the subject will be followed 
 
4 
Enrollment form must be signed by principal investigator or sub-investigator confirming eligibility. The completed/signed enrollment form and redacted source 
records (CT scan report confirming progression on prior treatment) must be faxed to number provided in the Study Reference Manual for approval by Sponsor 
and/or designee. Subjects must initiate treatment within 2 weeks of approved enrollment. 
5 
Height is measured without shoes.  
6 
Biopsy (pre- and post-treatment): Image-assisted core needle biopsy must be obtained at any accessible tumor site (primary preferred, metastatic site 
acceptable); fine needle aspirations are not acceptable. Baseline biopsy must be performed after subject eligibility is confirmed and must NOT be performed on 
the same day as pembrolizumab or CRS-207 administration.  Post-treatment biopsy must be performed between day 8-15 post-Cycle 2 CRS-207 infusion and 7 
days prior to Cycle 3. Collect serum/plasma and whole blood for PBMC on same day as post-treatment biopsy. If unscheduled biopsies are performed while 
subject is on treatment, retain a sample for Sponsor research purposes. Biopsy collection and processing instructions are provided in the Laboratory Manual.  
7 
Archived tumor tissue: Refer to Laboratory Manual for additional instructions. 
8 
CT scan of the thorax and abdomen. If CT contraindicated, an MRI should be performed. If subject has history of treatment for brain metastases, a baseline brain 
CT with contrast or MRI within 14 days prior to first dose of study drug must be negative for new brain metastases. CT scans must be done at Screening and up 
to 7 days prior to dosing every other cycle starting at Cycle 3 (e.g. Cycles 3, 5, 7, etc.).  CT scans should follow the calendar and shouldn’t be adjusted for dose 
delays. Tumor measurement and response assessment will be done per modified RECIST for MPM.  If radiographic disease progression is observed, another 
scan should be done at least 4 weeks later to confirm the disease progression prior to treatment discontinuation.  Sites must submit a copy of each scan on CD or 
other image media to the Sponsor; all protected health information (e.g. name, medical record number, etc.) must be redacted. Instructions for submission of 
scans are provided in the Study Reference Manual. 
9 
Pulmonary function tests (spirometry) for FVC and FEV1 performed at Screening and up to 7 days prior to dosing every other cycle starting at Cycle 3 (e.g. 
Cycles 3, 5, 7, etc.). 
10 
Electrocardiogram: Perform routine 12-lead ECGs after the subject has rested in a supine position for ≥5 minutes. During Cycles 1 and 2 obtain ECG [heart 
rate, PR interval, QT interval, QRS duration, QTcF (Fridericia's correction), and QTcB (Bazett's correction)] (collected within approximately a 5-minute 
window) prior to, immediately after and 1 hour following each pembrolizumab and CRS-207 dose. If abnormal at 1-hour post-infusion, repeat until baseline 
achieved. Additional ECGs may be performed if clinically indicated.   
11 
Complete physical examination at Screening and EOT; symptom-directed physical examination at all other indicated visits (up to 3 days prior to dosing).   

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
14 
12 
At visits indicated obtain vital signs (blood pressure, pulse, respiratory rate, and temperature) and pulse oximetry. For each pembrolizumab infusion obtain vital 
signs pre- and post-infusion. For each CRS-207 infusion obtain vital signs pre- and every 30 minutes during CRS-207 infusion and every hour during observation 
period.  Pulse oximetry may be obtained if clinically indicated. 
13 
At Cycle 5 and beyond, follow-up contact for AEs and concomitant medications will be conducted 1 day after pembrolizumab and CRS-207 infusion.  
Document contact in the study records.  
14 
Survival follow-up: Subjects will be contacted every 3 months to collect survival and subsequent cancer-related treatments in the Follow-up Period. Document 
contact in the study records.  Blood will continue to be collected for CRS-207 surveillance at 
 
 
15 
Clinical Laboratory Samples may be collected and tested up to 3 days prior to dosing. 
16 
Virology screen includes HIV antibody, hepatitis B surface antigen, and hepatitis C antibody; additional virology may also be evaluated. Subjects who are 
hepatitis C antibody positive and confirmed negative viral load at Screening will be considered eligible. 
17 
Hematology: complete blood count (WBC, red blood cells, hematocrit, and hemoglobin) with differential including ANC, ALC and platelet count 
Serum chemistry: sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, creatinine, lactate dehydrogenase, ALT, AST, alkaline phosphatase, 
bilirubin (total, direct, indirect), total protein, albumin, calcium, magnesium, uric acid, and phosphate. 
18 
Coagulation panel: PT, INR, aPTT, D-dimers, fibrinogen collected during Cycles 1 and 2 prior to and 1-day post-CRS-207 infusion.  Additional samples for 
coagulation panel may be collected as clinically indicated. 
19 
Urinalysis: bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, protein, and specific gravity (with microscopy at Screening and EOT)  
20 
Thyroid panel: triiodothyronine (T3) or free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) 
21 
Pregnancy tests administered to WOCBP only: serum HCG is required at Screening; urine pregnancy tests allowed at subsequent time points. In case of delayed 
menstrual period (> 1 month) confirm absence of pregnancy prior to dosing. 
22 
CD4 and CD8 Counts and HLA typing are performed by central laboratory. Instructions for collection of the samples is provided in the Laboratory Manual. If 
HLA sample is rejected for analysis, an additional sample may be collected at a later time point 
23 
Immune monitoring: collect serum and plasma at visits indicated pre-pembrolizumab, pre-CRS-207(collect only if not same day dosing), and 18-24 hours and 7 
days post-CRS-207. At Cycle 2, blood for immune monitoring for the 7 days post CRS-207 infusion should be taken on same day as post-treatment biopsy (Day 
8-15).  Cycle 5 and beyond (at all Odd Numbered Cycles): collect blood prior to pembrolizumab infusion. Refer to Laboratory Manual for collection and 
processing requirements. 
24 
Whole blood for PBMC: At Cycle 2, blood for PBMC for the 7 days post CRS-207 infusion should be taken on same day as post-treatment biopsy (Day 8-15). 
Cycle 5 and beyond (at all Odd Numbered Cycles): collect blood prior to pembrolizumab infusion. Refer to Laboratory Manual for collection and processing 
requirements. 
25 
At EOT, blood for CRS-207 surveillance will be collected prior to initiation of antibiotics (if applicable, blood must also be collected through the central line 
port) to assess CRS-207 clearance. After EOT, blood will continue to be collected for CRS-207 surveillance at 
 
.  AESI will continue to be reported in the follow-up period (refer to Section 8.4) 
26 
Pembrolizumab will be administered at indicated cycles via IV infusion over approximately 30 minutes (at cycles with same-day dosing, pembrolizumab is 
administered first followed by CRS-207 infusion).  Obtain vital signs (BP, pulse, respiratory rate, temperature) prior to, and immediately following each 
pembrolizumab infusion.  If subjects on same-day dosing schedule experience severe infusion-related reactions related to the pembrolizumab infusion, the CRS-
207 infusion may be delayed to Day 2.  CRS-207 administration may be delayed up to 7 days following pembrolizumab administration (if subject is recovering 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
15 
from an AE); the Sponsor must be notified. If a dose of CRS-207 is delayed beyond 7 days post pembrolizumab, the dose of CRS-207 should be withheld until 
the next cycle. 
27 
CRS-207 pre-medications include 650 mg of acetaminophen (paracetamol; or maximum permitted by label) administered orally prior to each CRS-207 infusion; 
a minimum of 0.5 L normal saline administered immediately before CRS-207 infusion and 0.5 - 1 L after infusion is recommended. Additional fluids may be 
given for persistent tachycardia, fever, or hypotension at Investigator’s discretion. 
28 
CRS-207 will be administered at indicated cycles via IV infusion (1 × 109 CFU [starting dose] in sterile saline, USP) over approximately 1 hour; Refer to 
Pharmacy Manual for preparation and administration requirements). CRS-207 must not be administered via central venous catheter or infusion port. IV must 
not have in line filters.  Subjects will be observed at least 4 hours after the first CRS-207 infusion and the first cycle with same day dosing. For all subsequent 
infusions, observe subject at least 2 hours post-infusion. Subjects may be released once they are considered stable; fever alone does not preclude release. Blood 
samples must not be collected from any central line after infusion of CRS-207 for at least 4 days. 
29 
 
 
30 
CRS-207 shedding and clearance subject subset: samples are collected at select sites only. At Cycles 1 and 2 blood for CRS-207 clearance, urine, rectal swab, 
and throat swab for CRS-207 shedding will be collected at pre-CRS-207 infusion, and 4 hours (± 30 minutes), 18-24 hours, and 7 days post-CRS-207 infusion. 
Subjects with samples positive for the presence of CRS-207 will be re-tested until negative testing is confirmed at the direction of the Sponsor.  Refer to 
Laboratory Manual for collection and processing requirements. 
 
ABBREVIATIONS FOR Table 2-1 AND Table 2-2 
ALT = alanine aminotransferase; AE = adverse event; AESI = adverse event of special interest; ALC = absolute lymphocyte count; ANC = absolute neutrophil count; 
aPTT = activated partial thromboplastin time; AST=aspartate aminotransferase; CFU = colony-forming units; CT = computed tomography; ECOG = Eastern Cooperative 
Oncology Group; EOT = End of Treatment; FEV1 = forced expiratory volume in 1 second; FVC=forced vital capacity; HCG = human chorionic gonadotropin; HIV = 
human immunodeficiency virus; HLA = human leukocyte antigen; INR = international normalized ratio of prothrombin time; IV = intravenous; MPM = malignant pleural 
mesothelioma; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cells; PT = prothrombin time; RECIST = Response Evaluation Criteria in 
Solid Tumors; WBC = white blood cell; WOCBP = woman of childbearing potential. 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
16 
3 
TABLE OF CONTENTS 
2 
SYNOPSIS ......................................................................................................................... 2 
3 
TABLE OF CONTENTS ............................................................................................... 16 
3.1 
LIST OF TABLES ...................................................................................................... 20 
3.2 
LIST OF FIGURES .................................................................................................... 20 
4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................ 21 
5 
INTRODUCTION .......................................................................................................... 23 
5.1 
Malignant Mesothelioma ............................................................................................ 23 
5.1.1 Current Therapies for Malignant Mesothelioma................................................... 23 
5.2 
CRS-207 Immunotherapy ........................................................................................... 24 
5.2.1 Listeria monocytogenes-Based Immunotherapy ................................................... 24 
5.2.2 CRS-207 ................................................................................................................ 24 
5.2.3 Summary of Nonclinical Studies with CRS-207 .................................................. 25 
5.2.4 Summary of Clinical Studies with CRS-207 ........................................................ 25 
5.3 
Rationale for CRS-207 and Pembrolizumab Immunotherapy in Malignant Pleural 
Mesothelioma .............................................................................................................. 26 
5.3.1 CRS-207 Dose Selection Rationale ...................................................................... 27 
5.3.2 Pembrolizumab Dose Selection Rationale ............................................................ 28 
6 
STUDY OBJECTIVES ................................................................................................... 30 
7 
INVESTIGATIONAL PLAN ........................................................................................ 31 
7.1 
Study Design and Duration ......................................................................................... 31 
7.1.1 Discussion of Study Design .................................................................................. 33 
7.2 
Study Population ......................................................................................................... 33 
7.2.1 Inclusion Criteria .................................................................................................. 34 
7.2.2 Exclusion Criteria ................................................................................................. 35 
7.2.3 Dosing Eligibility and Delayed Dosing ................................................................ 37 
7.2.4 Subject Discontinuation ........................................................................................ 38 
7.2.4.1 
Stopping Rules ................................................................................................. 39 
7.3 
Study Treatments and Additional Medications........................................................... 39 
7.3.1 Safety Run-In Period............................................................................................. 39 
7.3.1.1 
Unacceptable Toxicity Criteria ........................................................................ 40 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
17 
7.3.1.2 
Safety Monitoring ............................................................................................ 41 
7.3.2 Method of Assigning Subjects to Treatment ........................................................ 41 
7.3.3 Blinding................................................................................................................. 41 
7.3.4 Investigational Product: CRS-207 ........................................................................ 41 
7.3.4.1 
Biosafety and Environmental Precautions ....................................................... 42 
7.3.4.2 
CRS-207 Administration ................................................................................. 42 
7.3.4.3 
CRS-207 Dose Modification ........................................................................... 43 
7.3.5 Investigational Product:  Pembrolizumab ............................................................. 43 
7.3.5.1 
Pembrolizumab Administration ....................................................................... 44 
7.3.5.2 
Dose modification and toxicity management for immune-related AEs 
associated with pembrolizumab ........................................................................................ 44 
7.3.6 Antibiotics ............................................................................................................. 47 
7.3.6.1 
Antibiotic Treatment for Persistent CRS-207 Infection .................................. 47 
7.3.7 Concomitant Medications and Procedures ............................................................ 47 
7.3.8 Prohibited Medications and Procedures ................................................................ 48 
7.3.9 Treatment Compliance .......................................................................................... 49 
7.4 
Study Assessments and Procedures ............................................................................ 49 
7.4.1 General Assessments ............................................................................................ 50 
7.4.1.1 
Informed Consent ............................................................................................ 50 
7.4.1.2 
Eligibility ......................................................................................................... 50 
7.4.1.3 
Demographics, Medical History, and Height .................................................. 50 
7.4.1.4 
Archived Tumor Tissue and Tumor Biopsies .................................................. 50 
7.4.2 Efficacy Measures ................................................................................................. 51 
7.4.2.1 
Tumor Imaging and Response Assessments ................................................... 51 
7.4.2.2 
Pulmonary Function Testing ........................................................................... 52 
7.4.2.3 
Survival Follow-Up ......................................................................................... 52 
7.4.3 Safety Assessments ............................................................................................... 52 
7.4.3.1 
Eastern Cooperative Oncology Group Scale of Performance Status .............. 53 
7.4.3.2 
Vital Signs and Pulse Oximetry....................................................................... 53 
7.4.3.3 
Physical Examination and Weight ................................................................... 53 
7.4.3.4 
Adverse Events ................................................................................................ 54 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
18 
7.4.3.5 
Concomitant Medications ................................................................................ 54 
7.4.3.6 
Electrocardiogram ........................................................................................... 54 
7.4.3.7 
Clinical Laboratory Evaluation for Safety ....................................................... 55 
7.4.4 Laboratory Assessments ....................................................................................... 55 
7.4.4.1 
Screening/Baseline-specific Laboratory Assessments .................................... 55 
7.4.4.2 
Safety Laboratory Assessments ....................................................................... 55 
7.4.4.3 
Blood for CRS-207 Surveillance ..................................................................... 56 
7.4.4.4 
Biomarker and Research Laboratory Assessments ......................................... 56 
7.4.5 Subset Studies ....................................................................................................... 57 
7.4.5.1 
CRS-207 Shedding and Clearance Subset ....................................................... 57 
7.4.6 Appropriateness of Measures ................................................................................ 57 
7.5 
Statistical Analysis ...................................................................................................... 58 
7.5.1 Sample Size Determination ................................................................................... 58 
7.5.2 General Considerations ......................................................................................... 59 
7.5.3 Subject Information .............................................................................................. 59 
7.5.4 Analysis Sets ......................................................................................................... 59 
7.5.5 Efficacy Analyses ................................................................................................. 59 
7.5.5.1 
Primary Efficacy Variable and Analysis ......................................................... 60 
7.5.5.2 
Secondary Efficacy Variables and Analyses ................................................... 60 
7.5.5.3 
Other Efficacy Variables and Analysis ........................................................... 60 
7.5.6 Safety Analyses ..................................................................................................... 61 
7.5.7 Research Laboratory Analyses ............................................................................. 61 
7.5.8 Timing of Analysis ............................................................................................... 61 
7.5.9 Data Monitoring Committee ................................................................................. 61 
8 
ADVERSE EVENT REPORTING ............................................................................... 62 
8.1 
Adverse Events ........................................................................................................... 62 
8.1.1 Assessment of Adverse Events by the Investigator .............................................. 63 
8.2 
Serious Adverse Events .............................................................................................. 65 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators .............................. 66 
8.3.1 Initial Reports ........................................................................................................ 66 
8.3.2 Safety Reporting Contact Information .................................................................. 66 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
19 
8.3.3 Expedited Reporting Requirements ...................................................................... 66 
8.3.4 Follow-Up Reports................................................................................................ 66 
8.4 
Events of Clinical Interest ........................................................................................... 67 
8.5 
Adverse Events of Special Interest ............................................................................. 67 
8.5.1 Confirmed Listeria Infection ................................................................................. 67 
8.5.2 Suspected (Unconfirmed) Infection with CRS-207 or Listeria ............................ 68 
8.6 
Pregnancy Reporting ................................................................................................... 68 
9 
DATA MANAGEMENT AND RECORD KEEPING ................................................ 69 
9.1 
Data Handling ............................................................................................................. 69 
9.2 
Data Entry ................................................................................................................... 69 
9.3 
Medical Information Coding ....................................................................................... 69 
9.4 
Data Validation ........................................................................................................... 69 
9.5 
Record Keeping .......................................................................................................... 69 
10 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL ....................... 71 
10.1 
Ethical Conduct of the Study ...................................................................................... 71 
10.2 
Investigator Requirements .......................................................................................... 71 
10.2.1 Disposition and Accountability of Investigational Products ................................ 71 
10.3 
Institutional Review Board/Ethics Committee ........................................................... 72 
10.4 
Informed Consent........................................................................................................ 72 
10.5 
Study Monitoring Requirements ................................................................................. 72 
10.6 
Disclosure of Data ....................................................................................................... 73 
10.7 
Retention of Records ................................................................................................... 73 
10.8 
Publication Policy ....................................................................................................... 73 
10.9 
Financial Disclosure .................................................................................................... 74 
10.10 Insurance and Indemnity ............................................................................................. 74 
10.11 Legal Aspects .............................................................................................................. 74 
11 
REFERENCES ................................................................................................................ 75 
SIGNATURE PAGE ................................................................................................................... 78 
INVESTIGATOR AGREEMENT ............................................................................................ 79 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
20 
3.1 
LIST OF TABLES 
Table 2-1  Schedule of Events: Same-day (D1) Dosing Regimen1 .............................................. 10 
Table 2-2: Schedule of Events: Consecutive-day (Day 1 and 2) Dosing Regimen (for Subjects 
with Tolerability Issues)1 ............................................................................................ 12 
Table 7-1. Dosing-Eligibility Requirements ................................................................................ 37 
Table 7-2  ADU-CL-13 Study Treatment Course ......................................................................... 39 
Table 7-3  Safety Run-in Dose Levels and Dose Reduction ........................................................ 40 
Table 7-4  Dose modification and toxicity management guidelines for immune-related AEs 
associated with pembrolizumab .................................................................................. 45 
 
3.2 
LIST OF FIGURES 
Figure 7.1   
ADU-CL-13 Study Schema .................................................................................. 31 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
21 
4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
AE 
AESI 
Adverse event 
Adverse event of special interest 
ALC 
Absolute lymphocyte count 
ANC 
Absolute neutrophil count 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
BOR 
Best overall response 
CFR 
Code of Federal Regulations 
CFU 
Colony-forming units 
CR 
Complete response 
CRA 
Clinical research associate 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria For Adverse Events 
DOR 
Duration of response 
EAS 
Evaluable analysis set 
EC 
Ethics committee 
ECG 
ECI 
Electrocardiogram 
Event of clinical interest 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
ELISA 
Enzyme-linked immunosorbent assay 
EOT 
End of Treatment 
EU 
European Union 
FAS 
Full analysis set 
FDA 
United States Food and Drug Administration 
FEV1 
Forced expiratory volume in 1 second 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony-stimulating factor 
GM-CSF 
Granulocyte-macrophage colony-stimulating factor 
GVAX pancreas 
Irradiated, whole-cell, allogeneic tumor immunotherapy 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council on Harmonisation 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
22 
Abbreviation 
Definition 
IHC 
Immunohistochemistry 
INR 
International normalized ratio of prothrombin time 
IRB 
Institutional Review Board 
irRC 
immune-related RECIST 
IV 
Intravenous 
LADD 
Live, attenuated, double-deleted 
Lm 
Listeria monocytogenes 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major histocompatibility complex 
MPM 
Malignant pleural mesothelioma 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute  
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cells 
PD-1 
programmed death receptor-1 
PD-L1 
programmed death receptor ligand-1 
pembro 
pembrolizumab 
PFS 
Progression-free survival 
PR 
Partial response 
PT 
Prothrombin time 
Q3W 
Once every 3 weeks 
Q6W 
Once every 6 weeks 
RECIST 
Response evaluation criteria in solid tumors 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
TCR 
T cell receptor 
ULN 
Upper limit of normal 
WBC 
White blood cell 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
23 
5 
INTRODUCTION 
5.1 
Malignant Mesothelioma 
Mesothelioma is a life-threatening disease. Of the three primary forms of mesothelioma (pleural, 
peritoneal, and pericardial), malignant pleural mesothelioma (MPM) is the most common, 
accounting for 70% of all cases (American Cancer Society, 2014; Ahmed, 2013). MPM is a rare 
malignancy associated in 90% of cases with exposure to insoluble asbestos fibers that embed in 
mesothelial cells causing inflammation and scarring (Bridda, 2007; Boffetta, 2007; Carbone, 
2012; Robinson, 2005; Spirtas, 1986). 
In asbestos-related cases, there is a latency period of 20 to 40 years from first exposure to 
diagnosis, such that diagnosis often occurs between 50 and 70 years of age (Robinson and Lake, 
2005). When symptoms arise, they are frequently mistaken for another condition. As a result, 
mesothelioma is usually diagnosed in the later stages of its progression, resulting in poor 
prognosis with a median survival of 10 to 17 months from symptom onset and 9 to 13 months 
from diagnosis (Spirtas, 1986). 
5.1.1 
Current Therapies for Malignant Mesothelioma 
The best-documented, potentially curative approach to MPM has been surgical MPM resection 
with the aim for microscopic complete resection. However, the majority of patients present with 
advanced disease and are therefore not suitable candidates for surgical resection (Robinson and 
Lake, 2005; Sugarbaker, 1993).  
For patients whose disease is unresectable or who otherwise are not candidates for surgery, 
pemetrexed in combination with cisplatin is standard of care first-line chemotherapy and has 
been approved by the United States Food and Drug Administration (FDA) and other health 
authorities for this indication (Rice, 2011). Data from a randomized Phase 3 clinical trial 
indicated treatment with pemetrexed and cisplatin led to an improvement in overall survival (OS) 
of 12.1 months compared to 9.3 months with cisplatin alone, with an objective response rate 
(ORR) of 41% (Hazarika, 2005; Vogelzang, 2003).  In a recent randomized Phase 3 clinical 
study, the addition of bevacizumab to pemetrexed and cisplatin chemotherapy significantly 
improved OS over pemetrexed and cisplatin alone (median: 18.8 months vs. 16.1 months, 
respectively; p=0.012). More Grade 3 or 4 events, including proteinuria, hypertension, and 
arterial thrombotic toxicities were observed in the bevacizumab treatment arm (Zalcman, 2015). 
There are no approved therapies for patients in second-line, therefore, new therapies are needed 
for patients whose disease progresses following first-line chemotherapy. Immunotherapy could 
improve outcomes by potentiating specific immune responses against tumor antigens. The 
presence of high levels of CD8+ tumor-infiltrating lymphocytes has associated with better 
prognosis in subjects undergoing extrapleural pneumonectomy for MPM, supporting the 
rationale for this approach (Anraku, 2008). 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
24 
5.2 
CRS-207 Immunotherapy 
5.2.1 
Listeria monocytogenes-Based Immunotherapy 
Listeria monocytogenes (Lm) is an attractive platform for presentation of tumor-associated 
antigens and activation of immune response directed against cancer cells. Lm provides both a 
potent stimulation of innate immunity and also induces an adaptive immune response through 
recruitment and activation of CD4+ and CD8+ T-cells specific for encoded heterologous antigens 
(Portnoy, 2002; Shen, 1995; Slifka, 1996; Bahjat, 2006).  
In wild-type form, Lm is a bacterium commonly found in soil and water, and may be present in a 
variety of raw and processed foods. Listeriosis is a foodborne illness caused by wild-type Lm 
which primarily affects pregnant women and immunocompromised individuals. To address this 
safety concern a live, attenuated, double-deleted Lm (LADD)-based immunotherapy platform 
was developed (ANZ-100). ANZ-100 has deletions of 2 genes, actA and inlB (Lm ∆actA/∆inlB). 
These genes encode the virulence-determinant proteins ActA and Internalin B, two proteins that 
facilitate cell-to-cell spread and invasion of nonphagocytic cells, in particular hepatocytes 
(Brockstedt, 2004). The deletions limit growth in the liver, a principal target organ of infection 
by wild-type Lm, by blocking direct hepatocyte infection via the InlB-hepatocyte growth factor 
receptor interaction and ActA-mediated cell-to-cell spread into hepatocytes from infected liver-
resident Kupffer cells (Portnoy, Auerbuch, Glomski, 2002; Dramsi, 1995). Uptake of ANZ-100 
by macrophages and other phagocytic cells in the liver and spleen is retained and results in a 
local inflammatory response as well as activation and recruitment of natural killer cells and T 
cells to the liver. In mice, ANZ-100 retains the immunostimulatory potency of wild-type Lm but 
with 1000-fold attenuation of virulence (Brockstedt, 2004). In a Phase 1 dose-escalation study, 
ANZ-100 doses up to 3 × 108 colony-forming units (CFU) administered by intravenous (IV) 
infusion in adults with carcinoma and liver metastases were well-tolerated (Le, Brockstedt. 
2012).  
5.2.2 
CRS-207 
Mesothelin is a tumor-associated antigen with limited expression on the surface of normal 
tissues, but highly expressed in many human tumors including virtually all mesothelioma 
(Hassan, 2004). Mesothelin is more highly expressed in mesotheliomas as compared to other 
pulmonary carcinomas, with expression by immunohistochemistry (IHC) analysis detected in 75 
to 100% of poorly differentiated epithelioid or tubopapillary cases (Miettinen, 2003). These 
features make mesothelin an attractive target for active tumor-specific immunotherapy.  
ANZ-100 was subsequently engineered to express mesothelin, resulting in CRS-207 
(Lm ΔactA/ΔinlB/hMeso). CRS-207 contains an expression cassette encoding human mesothelin 
integrated at the inlB locus. After uptake of CRS-207 by dendritic cells and macrophages, 
mesothelin is expressed and released into the cytosolic compartment and subsequently processed 
through the endogenous major histocompatibility complex (MHC) Class I presentation pathway, 
resulting in activation of mesothelin-specific cell-mediated immunity (Le, Brockstedt, 2012). 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
25 
Other mechanisms to activate mesothelin-specific, cell-mediated immunity may include uptake 
and cross-presentation of antigens by dendritic cells and other cells after infection by CRS-207 
and apoptosis. CRS-207 is a LADD construct rendering it greater than 1000-times less toxic in 
mice than wild-type Lm (Brockstedt, 2004). Nonclinical and clinical data are available and 
support continued clinical development.    
5.2.3 
Summary of Nonclinical Studies with CRS-207 
A series of nonclinical studies in rodents (mice) and non-human primates (cynomolgus 
macaques) evaluated the pharmacology, pharmacokinetics (PK) and toxicology of CRS-207. In 
these studies, CRS 207 elicited mesothelin-specific cellular immunity and therapeutic efficacy in 
tumor-bearing mice. Repeated-dose safety studies in cynomolgus macaques with CRS-207 and 
the parent strain, ANZ-100, resulted in an equivalent pro-inflammatory response characterized 
by transient fluctuations in selected hematological and clinical chemistry parameters and 
reversible histopathology. Findings of the repeated-dose studies were consistent with a systemic 
proinflammatory response to a bacterial infection. At the highest dose, CRS 207 was detected in 
the blood 24 hours after administration, but was undetectable at 72 hours. There were transient 
and dose dependent decreases in red blood cell, platelet and white blood cell counts. Hepatic and 
renal function changes were transient and generally less than two-fold from baseline. There were 
no discernible additive effects of repeat dosing. 
 
 
 
  
Overall, nonclinical studies support use of CRS-207 in humans at the proposed dose. A complete 
summary of nonclinical information for CRS-207 is provided in the Investigator’s Brochure (IB). 
5.2.4 
Summary of Clinical Studies with CRS-207 
CRS-207 is being evaluated in multiple clinical studies and multiple oncologic indications. CRS-
207, either alone or in combination (sequential or concomitant) with other investigational or 
approved agents, has been administered to more than 350 subjects with advanced cancers. A 
complete summary of current clinical information on CRS-207 is provided in the IB.  
A Phase 1, first-in-human, multiple-dose, dose-escalation trial (VAC07001) was completed in 
adults with treatment-refractory MPM, advanced NSCLC, or advanced carcinoma of the ovary or 
pancreas. The maximum tolerated dose (MTD) was 1 × 109 CFU; CRS-207 was generally well 
tolerated. While the study enrolled subjects with multiple disease types and was not powered to 
assess survival, 6/17 subjects (with prior immunotherapy or subsequent radiation) survived at 
least 15 months after receiving the first dose of CRS-207. 
CRS-207 has orphan drug designation for the treatment of MPM in the US and European Union 
(EU). The clinical development program in MPM currently consists of an open-label Phase 1B 
study (ADU-CL-02) evaluating CRS-207 (with and without low-dose cyclophosphamide [Cy]) 
with standard of care chemotherapy (pemetrexed and cisplatin) as a first-line therapy in patients 
who are not candidates for complete surgical resection. Initial response data from 36 evaluable 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
26 
patients post-CRS-207 and chemotherapy included 1 (3%) complete response (CR), 20/36 (56%) 
partial responses (PR) and 13/36 (36%) had stable disease. The interim median progression-free 
survival (PFS) was 7.6 months (95% CI: 7.1-10.1 months) (Hassan, 2016).  
Treatment emergent adverse events (TEAEs) temporally related to CRS-207 administration 
which are common and may vary in degree of severity include fevers, chills, nausea, vomiting, 
fatigue, headache, and hypotension. Changes in hepatic enzyme levels and hematological 
parameters (lymphopenia) are also anticipated to varying degrees of severity. These effects are 
likely a consequence of the mechanism of action of CRS-207 through the activation of the innate 
immune system and release of proinflammatory cytokines and chemokines. Some of these 
infusion-related events may be mitigated by pre-medication with acetaminophen and 
administration of saline prior to and following CRS-207 infusion. Based on available results 
from clinical studies, continued clinical development of CRS-207 is warranted. 
5.3 
Rationale for CRS-207 and Pembrolizumab Immunotherapy in Malignant 
Pleural Mesothelioma 
For patients with unresectable MPM or who otherwise are not candidates for surgery, 
pemetrexed and cisplatin is the standard of care as first-line chemotherapy but confers limited 
benefit. There is an unmet medical need for patients who have disease progression following at 
least one systemic chemotherapy regimen.  
The programmed death receptor-1 (PD-1) is a checkpoint protein on T cells that normally 
inhibits T cells from attacking other cells in the body. Overexpression of the programmed death 
receptor ligand-1 (PD-L1) on cancer cells further evades immune attack by T cells. PD-L1 is 
overexpressed in MPM and associated with poor prognosis (Alley, 2015). Checkpoint inhibitors, 
including antibodies targeting PD-1, block the PD-1/PD-L1 interaction and boost the immune 
response against cancer cells. Monoclonal antibodies targeting PD-1 include pembrolizumab 
(Merck, 2014) and nivolumab have been approved for use in multiple tumor types and are 
currently being studied in several additional indications including MPM. 
Initial results from studies with monoclonal antibodies targeting PD-1 have shown evidence of 
clinical benefit in subjects with previously-treated MPM. Preliminary results from a Phase 1B 
trial (KEYNOTE-028) of pembrolizumab in 25 subjects with PD-L1-positive MPM (80% with 
prior chemotherapy) showed a 24% ORR and 76% DCR. AEs related to pembrolizumab 
occurred in 15 subjects (60%); drug-related events in > 25% of subjects were nausea, fatigue, 
and decreased appetite. No deaths or discontinuations were attributable to treatment; 3 subjects 
(12%) had grade ≥3 AEs related to treatment (Alley, 2015). Interim analysis from a Phase 2 trial 
(NivoMes) of nivolumab in 18 subjects with previously-treated MPM showed 39% DCR and 
28% ORR (Quispel-Janssen, 2016).  
The addition of a checkpoint inhibitor to CRS-207 may enhance the immunotherapeutic potential 
of these agents by enabling stimulation of targeted immune responses to specific tumor antigens. 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
27 
 
 
 
 
 
Initial data from an ongoing 
clinical study of CRS-207 with agents targeting the PD1 blockade (i.e. nivolumab) suggests an 
acceptable tolerability profile.  
The current study is designed to evaluate whether CRS-207 with pembrolizumab effectively 
primes specific immune responses and results in clinical benefit for patients with MPM who 
failed prior therapy. It is hypothesized the expansion of tumor-specific T cells in context of 
blocking the PD-1/PD-L1 pathway may ultimately provide enhanced anti-tumor efficacy. 
Although there are no precedent data on the safety of CRS-207 and pembrolizumab combination, 
CRS-207 is currently being evaluated with the PD-1 inhibitor nivolumab in an investigator-
sponsored Phase 2 study (ADU-CL-06; NCT02243371). The study is evaluating survival, safety 
and immune response following treatment with CRS-207/GVAX pancreas/Cy with or without 
nivolumab in subjects with previously-treated pancreatic cancer. Initial data from this ongoing 
clinical study suggests an acceptable tolerability profile of both agents at full dose (CRS-207 1 × 
109 CFU with nivolumab at 3 mg/kg).  Refer to the Investigator’s Brochure for additional 
information. These data suggest that a dose escalation Phase 1 component in the current study is 
not required. 
5.3.1 
CRS-207 Dose Selection Rationale 
CRS-207 has been shown to be well-tolerated at the proposed route of administration and dose 
for this study (Le, Dubenksy, 2012). The dose of CRS-207 was chosen based on the Phase 1, 
dose-escalation study (VAC07001) in which 1 × 109 CFU was determined to be the MTD and 
shown to be well-tolerated in patients with advanced cancer (including MPM) and induced a 
mesothelin-specific immune response. The 1 × 109 CFU dose level was also used in the Phase 
1B trial (ADU-CL-02) in MPM where initial analysis demonstrates clinical response and 
acceptable tolerability (Hassan, 2015). CRS-207 dosing at 1 × 109 CFU has been associated with 
mostly limited and transient infusion-related reactions including fevers, chills, nausea, vomiting, 
fatigue, headache, and hypotension, and changes in hepatic enzyme levels and hematological 
parameters (lymphocyte counts). 
The initial CRS-207 dosing regimen (once every 3 weeks; Q3W) in this study was designed to 
synergize with pembrolizumab to optimally prime an immune response. If subjects are clinically 
stable and/or responding to treatment, CRS-207 infusions will continue Q6W to sustain the 
immune response. In other clinical studies, CRS-207 has been administered every 2 to 8 weeks.  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
28 
5.3.2 
Pembrolizumab Dose Selection Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
   
 
 
 
 
 
 
    
 
 
 
 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
29 
 
   
 
 
 
   

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
30 
6 
STUDY OBJECTIVES 
The objectives of the study are to: 
• Assess safety and tolerability of CRS-207 and pembrolizumab (Merck, 2014) 
• Evaluate the effect of CRS-207 and pembrolizumab on tumor response, pulmonary 
function, and survival 
• Characterize the immune response following administration of CRS-207 and 
pembrolizumab 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
31 
7 
INVESTIGATIONAL PLAN 
7.1 
Study Design and Duration 
ADU-CL-13 is a single-arm, open-label, multicenter Phase 2 study to evaluate the safety and 
efficacy of CRS-207 administered with pembrolizumab (Merck, 2014). The population for this 
study will consist of approximately 35 adults with histologically-confirmed MPM (epithelial or 
biphasic) whose disease has progressed after prior systemic chemotherapy. The study will 
consist of a Screening Period, Treatment Period (including a Safety Run-in), and a Follow-up 
Period (Figure 7.1). 
Figure 7.1   
ADU-CL-13 Study Schema 
 
 
ECOG = Eastern Cooperative Oncology Group; MPM = malignant pleural mesothelioma; QxW = every x weeks 
 
CRS-207 and pembrolizumab will be administered in 3-week cycles.  For Cycle 1, 
pembrolizumab (200 mg) will be administered by intravenous infusion (IV) over 30 minutes on 
Day 1 and CRS-207 (starting dose 1 × 109 colony-forming units [CFU]) will be administered IV 
over 1 hour on Day 2. If the infusions are well tolerated, pembrolizumab and CRS-207 may be 
administered on the same day (Day 1) for subsequent cycles. After 4 cycles, pembrolizumab will 
continue to be administered on Day 1 at each treatment cycle (every 3 weeks; Q3W); CRS-207 
will be administered once every 6 weeks (i.e. every other treatment cycle; Q6W). Alternatively, 
study drug administration may revert back to consecutive day-dosing regimen as performed in 
Cycle 1 (Day 1 pembrolizumab and Day 2 CRS-207). Treatment cycles with pembrolizumab will 
continue for up to 35 cycles as long as there is adequate safety and potential for clinical benefit. 
After cycle 35, subjects may receive CRS-207 monotherapy if subject meets dosing eligibility, is 
clinically stable, and the subject is deriving clinical benefit. If radiographic disease progression is 
observed, clinically stable subjects who meet dosing eligibility may continue to receive CRS-207 
and pembrolizumab at the discretion of the Investigator. Subjects who experience unacceptable 
toxicity(ies) related to CRS-207 or pembrolizumab may continue on study and receive CRS-207 
or pembrolizumab monotherapy with approval from Medical Monitor. Subjects who experience 
unacceptable toxicity(ies) related to both CRS-207 and pembrolizumab in Cycle 1 should be 
discontinued from the treatment.  However, if in the opinion of the investigator, the subject is 
deriving clinical benefit from the study treatment, the subject may be allowed to continue with 
treatment after discussion with the Medical Monitor.     

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
32 
A Safety Run-in will be completed since there are no precedent data on the use of 
pembrolizumab with CRS-207. Treatment of the first 6 subjects will be staggered, with no more 
than 1 subject treated per week; subjects will be monitored for safety during the first 28 days (at 
least through 7 days after the Cycle 2 dose). During the Safety Run-in, evaluable subjects are 
defined as those who remain on study for the 28-day monitoring period, subjects with 
unacceptable toxicity, and subjects who are discontinued for safety reasons at the Investigator’s 
discretion (even if criteria for unacceptable criteria are not met).  In the event 2 subjects in the 
first 6 treated experience unacceptable toxicity(ies), the Safety Review Team will be convened to 
determine if the dose of CRS-207 will be reduced in subsequently enrolled subjects in half-log 
increments.   
Safety data including all unacceptable toxicities will be reviewed by a Safety Review Team 
comprised of participating investigators in the study, the Medical Monitor, and representatives of 
the Sponsor. Once the Safety Run-in is complete, safety will continue to be evaluated on an 
ongoing basis in this open-label study. Cumulative clinical experience with CRS-207 and 
pembrolizumab will be used to assess whether adverse events (AEs) are considered expected.  If 
>33% of subjects dosed experience unacceptable toxicities attributable to study drug(s), the 
Safety Review Team will be convened to determine if dosing will be suspended. 
The schedule of events is provided in Table 2-1 or Table 2-2 for subjects who experience 
tolerability issues and continue to follow the consecutive-day dosing regimen). Tumor imaging 
and pulmonary function will be assessed at baseline (Screening) and during the Treatment Period 
approximately every 6 weeks starting at Cycle 3. Tumor measurement and assignment of 
response will be determined by local Investigators using the modified response evaluation 
criteria in solid tumors (modified RECIST) for MPM (Byrne and Nowak, 2004). If radiographic 
disease progression is observed, another scan should be done at least four weeks later to confirm 
disease progression prior to treatment discontinuation. Peripheral blood will be collected to 
assess immune responses directed against L. monocytogenes, mesothelin, and other tumor-
associated antigens. Paired tumor biopsies will be collected at Screening and during Cycle 2 to 
explore the association of programmed death receptor ligand-1 (PD-L1) expression and tumor-
infiltrating lymphocyte characteristics with clinical responses.  
The Treatment Period is defined as the time from the first dose of study drug administration until 
discontinuation of both CRS-207 and pembrolizumab, and completion of an End of Treatment 
(EOT) visit. All subjects must complete an End of Treatment (EOT) visit no more than four 
weeks following the final dose of study drug and/or prior to receipt of other cancer-related 
treatment. Subjects will be administered antibiotics at the EOT visit to eliminate any potentially 
residual CRS-207 (refer to Section 7.3.6.1).   
At the end of the Treatment Period, subjects will enter the Follow-up Period of the study and will 
be followed for survival and subsequent cancer-related therapies every 3 months until death or 
close of study by the Sponsor. Sites will attempt to obtain vital status data from public records or 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
33 
other external sources where possible if a subject withdraws consent from study (i.e. refuse 
follow-up for vital status) or is documented as lost to follow up. 
7.1.1 
Discussion of Study Design 
The study was designed as a single-arm, open-label, multicenter Phase 2 study. The study is 
intended to provide the maximum amount of information regarding CRS-207 and 
pembrolizumab safety and tolerability, along with indicators of clinical efficacy and overall 
survival. Paired tumor biopsies and blood samples will provide an initial investigation into the 
mechanism of action of this regimen.  
There are currently no approved therapies beyond first-line treatment of MPM. Given the life-
threatening nature of the disease, a placebo-controlled trial is not appropriate in this setting. 
Since all subjects will receive the same investigational products, randomization and blinding are 
unnecessary; study drug will be provided open-label. The study is being conducted as a single-
arm trial to evaluate initial safety and efficacy signals before initiating a larger randomized trial. 
For the first cycle, pembrolizumab and CRS-207 will be dosed on consecutive days 
(pembrolizumab on Day 1 and CRS-207 on Day 2).  If Cycle 1 is well tolerated, dosing of both 
agents will occur on the same day (Day 1) for subsequent cycles.  Based on prior clinical 
experience and expected infusion reactions, it is anticipated that the same-day regimen will be 
tolerated and more convenient for patients.  A Safety Run-in is planned to monitor safety for the 
first 6 subjects.   
The sample size is intended to explore whether the proportion responding to CRS-207 and 
pembrolizumab is similar to or better than what is expected based on data from other clinical 
studies with checkpoint inhibitors in subjects with MPM. The estimate of ORR used for sample 
size determination is based on a review of published literature, where Investigator-assessed 
response rates from 24% (Alley, 2015) to 28% (Quispel-Janssen, 2016) were reported in studies 
of patients with MPM. Since these studies included all histological subtypes (sarcomatoid, 
epithelial and biphasic) and some studies required confirmation of PD-L1 expression prior to 
treatment, there is no direct published historical comparison in a similar population as intended 
for this study, however due to the lower expression of PD-L1 in the epithelial subtype (Cedrés, 
2015), observed response rates may be lower than the published studies. 
7.2 
Study Population 
The population for this study will consist of approximately 35 adults with histologically-
confirmed MPM (epithelial or biphasic with < 50% sarcomatoid) whose disease has progressed 
following at least one prior systemic chemotherapy regimen for advanced disease. Prior 
treatment must have included pemetrexed (or anti-folate) in combination with a platinum agent 
since this is approved therapy for MPM and recognized as standard of care in clinical practice. 
Individuals with immunosuppressive disorders or who require immunosuppressive medications 
will be excluded. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
34 
and serum albumin levels serve as prognostic indicators of participants more likely to benefit 
from treatment.  
7.2.1 
Inclusion Criteria 
Individuals eligible to participate in this study must meet all of the following criteria: 
1. Histologically-confirmed epithelial or biphasic MPM; biphasic tumors must have a 
predominantly (≥50%) epithelial component  
2. No more than 2 prior lines of anti-cancer therapy, one of which must have included 
pemetrexed and a platinum.  Documented radiographic progression of disease after treatment 
with pemetrexed and a platinum is required. 
3. Measurable disease as defined by modified RECIST for MPM 
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 
5. Adequate organ and marrow function at Screening, as defined by: 
• White blood cell count ≥ 3000/ µL 
• Absolute neutrophil count ≥ 1500/µL 
• Absolute lymphocyte count ≥ 800/µL 
• Platelet count ≥ 100,000/µL 
• Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), or ≤ 3 × institutional ULN if 
due to Gilbert’s disease 
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × 
institutional ULN or ≤ 5 × ULN for subjects with liver metastases 
• Albumin ≥ 3.0 g/dL 
• Serum creatinine ≤1.5 × institutional ULN 
• Hemoglobin ≥ 9.0 g/dL 
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN and activated 
partial thromboplastin time (aPTT) ≤1.5 × ULN (if receiving anticoagulant therapy, 
values should be within therapeutic range of intended use) 
Any Grade 3 or higher abnormality in any serum chemistry or hematology parameter must be 
discussed and approved by the Medical Monitor prior to enrollment (even if considered not 
clinically significant) 
6. Aged 18 years and over 
7. Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) ≥ 45% of 
predicted value as measured by spirometry; and oxygen saturation ≥ 90% on room air as 
measured by pulse oximeter 
8. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must 
use highly effective contraception [per (CTFG, 2014)] throughout the Treatment Period 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
35 
(from first dose and through 120 days after final dose of study drug). Contraception must 
include at least one barrier method to minimize risk of fluid transmission. 
9. Provide written informed consent and is willing and able to comply with all study 
procedures. 
7.2.2 
Exclusion Criteria 
Individuals who meet any of the following exclusion criteria will not be eligible to participate in 
the study: 
1. Pleurodesis within 14 days prior to first dose of study drug 
2. Has a diagnosis of immunodeficiency, receiving TNF pathway inhibitors, PI3 kinase 
inhibitors, chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone 
equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first 
dose of study drug 
3. Active second malignancy with the exception of any of the following: 
• Adequately treated basal cell carcinoma  
• Squamous cell carcinoma of the skin, or in situ cervical cancer 
• Low-risk prostate cancer (i.e. Gleason score < 7 and prostate specific antigen < 10 
ng/mL); or 
• Any other cancer from which the individual has been disease-free for ≥ 3 years 
4. Untreated or unstable brain metastases. Individuals with treated (surgically excised or 
irradiated) and stable brain metastases are eligible as long as the subject has adequately 
recovered from treatment and the treatment was ≥ 28 days prior to first dose of study drug. A 
baseline brain computed tomography (CT) with contrast or magnetic resonance imaging 
(MRI) within 14 days prior to first dose of study drug must be negative for new brain 
metastases. 
5. Prior anti-cancer monoclonal antibody within 4 weeks prior to first dose of study drug, or not 
recovered from adverse effects due to agents administered more than 4 weeks earlier 
6. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks 
prior to first dose of study drug 
7. Ongoing adverse effects (i.e. ≤ Grade 1 or at baseline) due to a previously administered anti-
cancer agent. Individuals with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception 
to this criterion 
8. History of (non-infectious) pneumonitis that required steroids or current pneumonitis 
9. History of interstitial lung disease  
10. Received transfusion of blood products (including platelets or red blood cells) or 
administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant 
erythropoetin) within 4 weeks prior to first study drug administration 
11. Active infection requiring systemic therapy 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
36 
12. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agents targeting other 
checkpoint pathways (e.g. CTLA-4) 
13. Prior immunotherapy with CRS-207 or any other Listeria-based agent, therapeutic cancer 
vaccine, or adoptive T cell immunotherapy 
14. Received any prophylactic vaccine within 14 days of first dose of study drug or received a 
live vaccine within 30 days of planned start of study therapy.  Seasonal flu vaccines that do 
not contain live virus are permitted. 
15. Participated in any other study in which receipt of an investigational new drug, or 
investigational device occurred within 28 days of first dose of study drug 
16. Clinically significant heart disease (such as uncontrolled angina, myocardial infarction within 
3 months of study initiation, congestive heart failure, or New York Heart Association Class 
III or IV heart failure) 
17. Know valvular heart disease that requires antibiotic prophylaxis for prevention of 
endocarditis 
18. Known allergy to both penicillin and sulfa drugs 
19. Known or suspected allergy or hypersensitivity to yeast or any other component of CRS-207 
(e.g. glycerol) or pembrolizumab; or history of severe hypersensitivity (≥ Grade 3) to  
pembrolizumab and/or any of its excipients. 
20. History of autoimmune disease that has required systemic treatment in the past 2 years, 
including:  
• Inflammatory bowel disease (including ulcerative colitis and Crohn’s Disease) 
• Rheumatoid arthritis 
• Systemic progressive sclerosis (scleroderma) 
• Systemic lupus erythematosus 
• Autoimmune vasculitis (e.g. Wegener’s granulomatosis) 
• Central nervous system or motor neuropathy considered of autoimmune origin (e.g. 
Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis) 
Individuals with vitiligo, moderate to severe psoriasis, Sjogren’s Syndrome, interstitial 
cystitis, Graves’ or Hashimoto’s Disease, celiac disease, diabetes mellitus type 1, or 
hypothyroidism stable on hormone replacement will be allowed with Medical Monitor 
approval. 
21. Received a diagnosis of human immunodeficiency virus (HIV) 
22. Received a diagnosis of hepatitis B, or hepatitis C for which there is no clear evidence of 
natural immunity, immunity subsequent to vaccination, or successful eradication of the virus 
following antiviral therapy (individuals who are hepatitis C antibody positive may be 
enrolled if negative viral load confirmed at Screening) 
23. If WOCBP, pregnant or breastfeeding; negative pregnancy status must be confirmed within 
24 hours of first dose of study drug 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
37 
24. Implanted medical devices that pose high risks for colonization and cannot be easily removed 
(e.g., artificial heart valves, pacemakers, prosthetic joints, orthopedic screw(s), metal 
plate(s)) if infection occurs. Other common devices such as venous access devices (e.g., Port-
a-Cath or Mediport) may be permitted as well as arterial and venous stents and dental and 
breast implants that were placed more than 3 months prior to first dose of study drug 
25. Major surgery or significant traumatic injury occurring within 28 days prior to first dose of 
study drug. If subject received major surgery, they must have recovered adequately from the 
toxicity and/or complications from the intervention prior to starting therapy. 
26. Unhealed wound or ulcer; or a bone fracture considered non-healing 
27. History or evidence of inherited bleeding diathesis or coagulopathy 
28. Unable or unwilling to withhold or discontinue any prohibited or restricted 
medications/procedures for the specified periods during the study 
29. Intercurrent illness that is either life-threatening or of clinical significance such that it might 
limit compliance with study requirements, or in the Investigator’s assessment would place 
the subject at an unacceptable risk for study participation 
7.2.3 
Dosing Eligibility and Delayed Dosing 
Subjects must have adequate organ function confirmed (as defined by the laboratory values in 
Table 7-1 prior to each dosing cycle where CRS-207 is administered; laboratory tests may be 
performed up to 3 days before dosing. 
Table 7-1. Dosing-Eligibility Requirements 
Hematologic 
Renal 
Hepatic 
WBC ≥ 3000/µL 
ANC ≥ 1000/µL 
Platelets ≥ 90,000/µL 
Hemoglobin  ≥ 8 g/dL 
Creatinine ≤ 1.5 × ULN  
AST/ALT ≤ 5× ULN 
Bilirubin ≤ 1.5× ULN OR ≤ 3 
× ULN if due to Gilbert’s 
disease 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; 
ULN = institutional upper limit of normal; WBC = white blood cell 
Subjects who do not meet dosing eligibility requirements will be monitored; dosing may be 
delayed up to 2 weeks, after which time it will be considered missed and the subject would 
continue onto the next scheduled dose. If a dose is delayed more than 2 weeks, contact the 
Medical Monitor for further instruction on continued dosing. 
Pembrolizumab may be administered up to 3 days before or after the scheduled Day 1 of each 
cycle due to administrative reasons (refer also to Section 7.3.5.1). If subjects on same-day dosing 
schedule experience severe infusion-related reactions related to the pembrolizumab infusion, the 
CRS-207 infusion may be delayed to Day 2. If the subject experiences a new AE or is recovering 
from an AE, CRS-207 administration may be delayed up to 7 days following pembrolizumab 
administration; the Sponsor must be notified. If a dose of CRS-207 is delayed beyond 7 days 
post pembrolizumab, the dose of CRS-207 should be withheld until the next cycle. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
38 
Dosing interruptions are permitted in the case of medical / surgical events or logistical reasons 
not related to study therapy (e.g. elective surgery, unrelated medical events, vacation, and/or 
holidays). Subjects should be placed back on study therapy within 3 weeks of the scheduled 
interruption, unless otherwise discussed with the Sponsor. The reason for interruption should be 
documented in the Subject’s study record. 
7.2.4 
Subject Discontinuation 
Subjects will be encouraged to complete the study; however, they may voluntarily withdraw 
from treatment or the study at any time. The Investigator will provide a written explanation 
describing the reason for discontinuation from treatment or study in a source document, which 
will be entered into the electronic case report form (eCRF). Subjects who wish to discontinue 
treatment will be encouraged to complete the planned administration of antibiotics, complete 
EOT assessments, post-treatment monitoring for CRS-207, and participate in the Follow-up 
Period. In the case of subjects lost to follow-up, attempts to contact the subject must be made and 
documented in the subject’s study records. Sites will attempt to obtain vital status data from 
public records or other external sources where possible if a subject withdraws consent from study 
(i.e. refuse follow-up for vital status) or is lost to follow up.   
A subject in this clinical study may be discontinued from treatment for any of the following 
reasons: 
• The subject withdraws consent or requests discontinuation for any reason 
• Occurrence of any medical condition or circumstance that exposes the subject to 
substantial risk and/or does not allow the subject to adhere to the requirements of the 
protocol 
• Any SAE, clinically significant AE, severe laboratory abnormality, intercurrent illness, or 
other medical condition which indicates to the Investigator that continued participation is 
not in the best interest of the subject 
• Pregnancy 
• Subject failure to comply with protocol requirements or study-related procedures  
• Termination of the study by the Sponsor or the regulatory authority 
Subjects who experience unacceptable toxicity(ies) related to CRS-207 or pembrolizumab may 
continue on study and receive CRS-207 or pembrolizumab monotherapy. Subjects who 
experience unacceptable toxicity(ies) related to both CRS-207 and pembrolizumab in Cycle 1 
should be discontinued from the treatment.  However, if in the opinion of the investigator, the 
subject is deriving clinical benefit from the study treatment, the subject may be allowed to 
continue with treatment after discussion with the Medical Monitor.  Alternatively, study drug 
administration may revert back to consecutive day-dosing regimen as performed in Cycle 1.  If 
subjects experience unacceptable toxicity(ies) related to both CRS-207 and pembrolizumab that 
is ≥ Grade 3, treatment should be discontinued and Medical Monitor notified. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
39 
7.2.4.1 
Stopping Rules 
There are no formal stopping rules for this study. Once the Safety Run-in Period is complete, 
safety will continue to be evaluated on an ongoing basis in this open-label study. Cumulative 
clinical experience with CRS-207 and pembrolizumab will be used to assess whether AEs are 
considered expected.  If >33% of subjects dosed experience unacceptable toxicities attributable 
to study drug(s), the Safety Review Team will be convened to determine if dosing will be 
suspended. 
7.3 
Study Treatments and Additional Medications 
Subjects will receive the assigned treatment course described in Table 7-2. 
Table 7-2  ADU-CL-13 Study Treatment Course 
Study Drug  
Dose / Route 
Treatment Course 
Pembrolizumab 
200 mg administered IV over 
30 min (-5 min/+10 min) 
Day 1 of each cycle   
CRS-207 
1×109 CFU administered IV 
over ~ 1 hour 
Day 2 of Cycle 1 
Day 1 of Cycle 2, 3, 4; Q6W thereafter 1 
CFU = colony-forming unit; IV = intravenous; Q6W = every 6 weeks 
1 Subjects who experience tolerability issues may continue to follow the consecutive-day dosing regimen as in 
Cycle 1 and follow the Schedule of Events for Consecutive Day Dosing (Table 2-2). 
7.3.1 
Safety Run-In Period 
A Safety Run-in will be completed since there are no precedent data on the use of 
pembrolizumab with CRS-207. Treatment of the first 6 subjects will be staggered, with no more 
than 1 subject treated per week. Subjects will be monitored for unacceptable toxicities during the 
Safety Run-in Period [the first 28 days (through 7 days after the Cycle 2 dose)].  During the 
Safety Run-in evaluable subjects are defined as those who remain on study for the 28-day 
monitoring period, subjects with unacceptable toxicity, and subjects who are discontinued for 
safety reasons at the Investigator’s discretion (even if criteria for unacceptable criteria are not 
met).  In the event 2 subjects in up to 6 experience unacceptable toxicity(ies) during the Safety 
Run-in Period, the Safety Review Team will be convened to determine if subsequent subjects 
enrolled will be administered CRS-207 at a dose reduced by a half-log (dose level -1). In the 
event of 2 subjects in up to the next 6 subjects treated experience unacceptable toxicity(ies), the 
Safety Review Team will reconvene to determine if the dose for CRS-207 will be further 
reduced by a half-log (dose level -2) for the remaining subjects to be enrolled. The medical 
monitor, participating investigators, and Sponsor may request that the Safety Review Team 
convene at any time during the Safety Run-in Period to review and evaluate available safety data. 
The dose levels and dose reduction permutations are provided in Table 7-3. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
40 
Table 7-3  Safety Run-in Dose Levels and Dose Reduction   
Dose level 
Pembrolizumab  
 
CRS-207 
  
1 
200 mg 
1 × 109 CFU 
-1 
-2 
200 mg 
200 mg 
3 × 108 CFU 
1 × 108 CFU 
Subjects who experience unacceptable toxicity(ies) related to CRS-207 or pembrolizumab may 
continue on study and receive CRS-207 or pembrolizumab monotherapy with approval from 
Medical Monitor. 
7.3.1.1 
Unacceptable Toxicity Criteria 
The unacceptable toxicity criteria will be any of the following unless clearly related to an 
alternative cause other than study drug:  
• 
Grade 5 toxicity  
• 
Grade 4 non-hematologic toxicity (not laboratory)  
• 
Grade 4 hematologic toxicity lasting ≥7 days  
• 
Grade 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal 
supportive care  
• 
Any Grade 3 or Grade 4 non-hematologic laboratory value if:  
o Medical intervention is required to treat the subject, or  
o The abnormality leads to hospitalization, or  
o The abnormality persists for >1 week  
• 
Grade 3 or 4 febrile neutropenia 
o Grade 3 is defined as ANC <1000/mm3 with a single temperature of >38.3 oC (101 oF) 
or a sustained temperature of ≥38 oC (100.4 oF) for more than one hour  
o  Grade 4 is defined as ANC <1000/mm3 with a single temperature of >38.3 oC (101 oF) 
or a sustained temperature of ≥38 oC (100.4 oF) for more than one hour, with life- 
threatening consequences and urgent intervention indicated  
• 
Thrombocytopenia <25,000/mm3 if associated with:  
o A bleeding event which does not result in hemodynamic instability but requires an 
elective platelet transfusion, or  
o A life-threatening bleeding event which results in urgent intervention and admission 
to an Intensive Care Unit  
• 
Delay of >8 days starting Cycle 2 due to study drug-related toxicity  
• 
Administration of systemic steroids to treat an immune-mediated reaction  
• 
Serum chemistry laboratory values consistent with Hy’s Law criteria (i.e. all 3 of the 
following must coexist):  
o ALT or AST ≥ 3 × ULN  
o Total bilirubin ≥ 2 × ULN  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
41 
o ALP < 2 × ULN  
Safety data and all unacceptable toxicities will be reviewed by the Safety Review Team comprised of 
participating investigators in the study, the Medical Monitor, and Sponsor representatives. Once the 
Safety Run-in is complete, safety will continue to be evaluated on an ongoing basis in this open-label 
study. Cumulative clinical experience with CRS-207 and pembrolizumab will be used to assess 
whether AEs are considered expected.  
Subjects who experience an unacceptable toxicity related to CRS-207 or pembrolizumab may 
continue on study and receive either pembrolizumab or CRS-207 monotherapy with approval by the 
Medical Monitor.  
7.3.1.2 
Safety Monitoring 
Safety data including all unacceptable toxicities will be reviewed by a Safety Review Team 
comprised of participating investigators in the study, the Medical Monitor, and Sponsor 
representatives. Following the safety run-in period, safety will continue to be evaluated on an 
ongoing basis. If >33% of subjects dosed experience unacceptable toxicities attributable to study 
drug(s), the Safety Review Team will be convened to determine if dosing will be suspended. 
Cumulative clinical experience with CRS-207 and pembrolizumab will be used to assess whether 
AEs are considered expected.   
Subjects who experience unacceptable toxicity(ies) related to CRS-207 or pembrolizumab may 
continue on study and receive CRS-207 or pembrolizumab monotherapy with approval from 
Medical Monitor.  Subjects who experience unacceptable toxicity(ies) related to both CRS-207 
and pembrolizumab in Cycle 1 should be discontinued from treatment.  However, if in the 
opinion of the investigator, the subject is deriving clinical benefit from the study treatment, the 
subject may be allowed to continue with treatment after discussion with the Medical Monitor.    
7.3.2 
Method of Assigning Subjects to Treatment 
All subjects will be sequentially assigned a unique subject identification number upon providing 
informed consent. The study is designed as a single-arm study; all subjects will receive CRS-207 
and pembrolizumab as indicated. 
7.3.3 
Blinding 
ADU-CL-13 is a single-arm, open-label study. Due to the expected infusion-related reactions and 
required pre-medications associated with CRS-207 administration, it is not feasible or necessary 
to conduct the study under blinded conditions. All study treatments will be administered open-
label; no study participants or site personnel will be blinded to study treatment. 
7.3.4 
Investigational Product: CRS-207 
CRS-207 is a LADD strain derived by deletion of actA and inlB coding sequences from a 
streptomycin-resistant, wild-type strain and insertion of the hMeso coding sequence. The CRS-

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
42 
207 drug product is formulated as 1 × 109 CFU suspended in 
 
, filled into a single-use 2-mL glass vial with a gray butyl stopper 
and aluminum crimp seal with a flip-off cap. CRS-207 is stored frozen at -60 ºC or colder until 
just before IV administration. CRS-207 is supplied by the Sponsor. Additional information on 
CRS-207 may be found in the Pharmacy Manual and IB. 
7.3.4.1 
Biosafety and Environmental Precautions 
In wild-type form, Lm is a bacterium commonly found in soil and water, and may be present in a 
variety of raw and processed foods. Listeriosis is a foodborne illness caused by wild-type Lm 
which primarily affects pregnant women and immunocompromised individuals. Direct human-
to-human spread of Lm is believed to be limited mainly to vertical transmission from mother to 
neonate. CRS-207 is a LADD construct originating from wild-type Lm which contains deletions 
of 2 virulence genes that render it greater than 1000-times less toxic than wild-type Lm in mice  
(Brockstedt, 2004). 
LADD-based immunotherapies (Lm ΔactA/ΔinlB) including CRS-207, have been designated as 
Risk Group 1 by the Aduro Institutional Biosafety Committee. Risk Group 1 is consistent with 
the guidance by the German ZKBS (Central Commission for Biological Safety) for classification 
of Lm strains with deletion in genes prFA, hly, actA, and plcB (1999). Individuals who prepare 
CRS-207 for infusion must take appropriate precautions (e.g. gloves, laboratory coat, face 
protection, needle stick or sharps precautions) to avoid contamination or direct contact with the 
agent. Once prepared for infusion, the chance for direct exposure to CRS-207 by study personnel 
should be greatly diminished. However, study personnel and staff should continue to adhere to 
the institutional guidelines for standard precautions. 
Based on nonclinical studies and available clearance and shedding data from clinical studies, a 
subject who receives CRS-207 is unlikely to spread an infection to others. Subjects receiving 
CRS-207 should be counseled to minimize the potential risk of spreading CRS-207 by practicing 
good health hygiene (e.g. hand-washing) as with any potential infectious agent, and adhering to 
protocol requirements for barrier method of contraception during sexual intercourse. 
7.3.4.2 
CRS-207 Administration 
CRS-207 is intended for IV administration (IV must not have in line filters). The intended dose 
of CRS-207 is 1 × 109 CFU diluted in sterile saline and administered by IV infusion. Additional 
details for storage and preparation of CRS-207 are provided in the study Pharmacy Manual. 
Use of Central Lines 
To avoid contamination of a central line (e.g. infusion ports, peripherally inserted central 
catheter) with CRS-207 during and after infusion: 
• CRS-207 must NOT be administered through a central line or infusion ports 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
43 
• Central lines must NOT be used or accessed for any reason once CRS-207 infusion has 
been initiated (including blood draws, medication administration or line flushing; blood 
draws prior to infusion through a port or central line are allowed) and through 4 days 
after infusion 
• Central lines must be clearly labeled with tape or other method indicating date when port 
may be used again after CRS-207 infusion 
Pre-Medication and Post-Infusion Observation 
Before each CRS-207 infusion, subjects should be pre-medicated with 650 mg (or maximum 
dose permitted by label) acetaminophen (paracetamol). Adequate hydration is important to 
mitigate infusion-related reactions. All subjects are required to receive a minimum of 0.5 L of 
normal saline immediately before CRS-207 infusion; an additional 0.5 - 1 L after infusion is 
recommended, as tolerated. Additional fluids may be given for persistent tachycardia, fever, or 
hypotension based on Investigator’s discretion.  
Subjects will be observed in the clinic for at least 4 hours after the first CRS-207 infusion and 
first cycle with same day dosing; and at least 2 hours following each subsequent infusion. 
Subjects should continue to be monitored after infusion and released once they are considered 
clinically stable. Vital signs will be monitored (Section 7.4.3.1). Presence of fever alone in the 
absence of other clinical signs and symptoms does not preclude the subject from being released. 
Hospital admissions for overnight monitoring will not be considered an SAE unless the event 
meets criteria for seriousness other than hospitalization.  
During and after CRS-207 infusions, subjects may experience fever, chills/rigor, blood pressure 
changes, nausea, and vomiting. Refer to Section 7.3.7 and the IB for additional details on CRS-
207 administration and supportive care. 
7.3.4.3 
CRS-207 Dose Modification 
CRS-207 at the proposed dose level has been well tolerated and dose reductions are not 
anticipated. The dose of CRS-207 may be reduced outside of the Safety Run-in period as 
recommended by the Safety Review Team.  However, in the event of AEs of concern that are 
attributable to CRS-207 the Medical Monitor should be contacted.  
7.3.5 
Investigational Product:  Pembrolizumab 
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 
and its ligands, PD-L1 and PD-L2. Pembrolizumab is an IgG4 kappa immunoglobulin with an 
approximate molecular weight of 149 kDa. Pembrolizumab is not currently approved for 
treatment of MPM and is being used as an investigational agent in this study. However, the 
approved package insert should be consulted for additional product information on storage, 
preparation and administration, contraindications, warnings/precautions, adverse reactions, and 
drug interactions. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
44 
Pembrolizumab for injection is a sterile, preservative-free, clear to slightly opalescent, colorless 
to slightly yellow solution that requires dilution for IV infusion. Each vial contains 100 mg of 
pembrolizumab in 4 mL of solution. Each 1 mL of solution contains 25 mg of pembrolizumab 
and is formulated in: L-histidine (1.55 mg), polysorbate 80 (0.2 mg), sucrose (70 mg), and Water 
for Injection, USP.  
7.3.5.1 
Pembrolizumab Administration 
Pembrolizumab will be diluted and administered as a dose of 200 mg using a 30-minute IV 
infusion. Sites should target infusion timing to be as close to 30 minutes as possible. However, 
given the variability of infusion pumps, a window between -5 minutes and +10 minutes is 
permitted (i.e. infusion time is 30 minutes -5 min/+10 min). Do not co-administer other drugs 
through the same infusion line. Vital signs (blood pressure, pulse, respiratory rate, temperature) 
will be measured pre- and post-infusion. 
Pembrolizumab infusions will be administered Q3W for up to 35 cycles. The Pharmacy Manual 
contains specific instructions for the preparation of the pembrolizumab infusion and 
administration of infusion solution. 
7.3.5.2 
Dose modification and toxicity management for immune-related AEs associated with 
pembrolizumab 
AEs associated with pembrolizumab exposure may represent an immunologic etiology. These 
immune-related AEs (irAEs) may occur shortly after the first dose or several months after the 
last dose of pembrolizumab treatment and may affect more than on body system simultaneously. 
Therefore, early recognition and initiation of treatment is critical to reduce complications.  Based 
on existing clinical trial data, most irAEs were reversible and could be managed with 
interruptions of pembrolizumab, administration of corticosteroids and/or other supportive care. 
For suspected irAEs, ensure adequate evaluation to confirm etiology or exclude other causes. 
Additional procedures or tests such as bronchoscopy, endoscopy, skin biopsy may be included as 
part of the evaluation. Based on the severity of irAEs, withhold or permanently discontinue 
pembrolizumab and administer corticosteroids. Dose modification and toxicity management 
guidelines for irAEs associated with pembrolizumab are provided in Table 7-4.  
 
 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
45 
 
Table 7-4  Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab 
 
General instructions: 
1. Corticosteroid taper should be initiated upon AE improving to Grade 1 or less and continue to taper over at least 4 weeks. 
2. For situations where pembrolizumab has been withheld, pembrolizumab can be resumed after AE has been reduced to Grade 1 or 0 and 
corticosteroid has been tapered. Pembrolizumab should be permanently discontinued if AE does not resolve within 12 weeks of last dose or 
corticosteroids cannot be reduced to ≤ 10 mg prednisone or equivalent per day within 12 weeks.  
3. For severe and life-threatening irAEs, IV corticosteroid should be initiated first followed by oral steroid. Other immunosuppressive treatment 
should be initiated if irAEs cannot be controlled by corticosteroids. 
Immune-related 
AEs 
Toxicity grade or 
conditions 
(CTCAEv4.0) 
Action taken to 
pembrolizumab 
irAE management with 
corticosteroid and/or other 
therapies  
Monitor and follow-up  
Pneumonitis  
Grade 2 
Withhold  
• Administer corticosteroids (initial 
dose of 1-2mg/kg prednisone or 
equivalent) followed by taper 
 
• 
Monitor subjects for signs and symptoms of 
pneumonitis 
• 
Evaluate subjects with suspected 
pneumonitis with radiographic imaging and 
initiate corticosteroid treatment 
• 
Add prophylactic antibiotics for 
opportunistic infections 
Grade 3 or 4, or 
recurrent grade 2 
Permanently 
discontinue 
Diarrhea / colitis  
Grade 2 or 3 
Withhold 
• Administer corticosteroids (initial 
dose of 1-2mg/kg prednisone or 
equivalent) followed by taper 
 
• 
Monitor subjects for signs and symptoms of 
enterocolitis (i.e. diarrhea, abdominal pain, 
blood or mucus in stool with or without 
fever) and of bowel perforation (i.e. 
peritoneal signs and ileus). 
• 
Subjects with ≥ Grade 2 diarrhea suspecting 
colitis should consider GI consultation and 
performing endoscopy to rule out colitis.  
• 
Subjects with diarrhea/colitis should be 
advised to drink liberal quantities of clear 
fluids.  If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be 
substituted via IV infusion. 
Grade 4 
Permanently 
discontinue 
AST / ALT 
elevation or 
Increased 
Bilirubin 
Grade 2 
Withhold 
• Administer corticosteroids (initial 
dose of 0.5- 1mg/kg prednisone or 
equivalent) followed by taper 
• 
Monitor with liver function tests (consider 
weekly or more frequently until liver 
enzyme value returned to baseline or is 
stable 
Grade 3 or 4  
Permanently 
discontinue 
• Administer corticosteroids (initial 
dose of 1-2mg/kg prednisone or 
equivalent) followed by taper 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
46 
Type 1 diabetes 
mellitus (T1DM) 
or 
Hyperglycemia 
 
Newly onset 
T1DM or  
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of β-cell 
failure 
Withhold 
• Initiate insulin replacement 
therapy for subjects with T1DM  
• Administer anti-hyperglycemic in 
subjects with hyperglycemia  
 
• 
Monitor subjects for hyperglycemia or other 
signs and symptoms of diabetes. 
Hypophysitis 
Grade 2 
Withhold 
• Administer corticosteroids and 
initiate hormonal replacements as 
clinically indicated.   
 
• 
Monitor for signs and symptoms of 
hypophysitis (including hypopituitarism and 
adrenal insufficiency)  
Grade 3 or 4  
Withhold or 
permanently 
discontinue1  
Hyperthyroidism  
Grade 2 
Continue  
• Treat with non-selective beta-
blockers (e.g. propranolol) or 
thionamides as appropriate  
• 
Monitor for signs and symptoms of thyroid 
disorders.  
 
Grade 3 or 4  
Withhold or  
Permanently 
discontinue1 
Hypothyroidism 
Grade 2-4 
Continue  
• Initiate thyroid replacement 
hormones (e.g. levothyroxine or 
liothyroinine) per standard of care 
• 
Monitor for signs and symptoms of thyroid 
disorders.  
 
Nephritis and 
renal dysfunction 
Grade 2 
Withhold  
• Administer corticosteroids 
(prednisone 1-2mg/kg or 
equivalent) followed by taper. 
• 
Monitor changes of renal function 
 
Grade 3 or 4  
Permanently 
discontinue 
All Other 
immune-related 
AEs 
Grade 3, or 
intolerable/ 
persistent Grade 2 
Withhold 
• Based on severity of AE 
administer corticosteroids  
• 
Ensure adequate evaluation to confirm 
etiology or exclude other causes 
 
Grade 4 or 
recurrent Grade 3  
Permanently 
discontinue 
NOTES:  
1. Withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician.   
2. For subjects with Grade 3 or 4 immune-related endocrinopathy where withhold of pembrolizumab is required, pembrolizumab may be resumed when 
AE resolves to ≤ Grade 2 and is controlled with hormonal replacement therapy or achieved metabolic control (in case of T1DM).   

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
47 
7.3.6 
Antibiotics 
To eliminate any potentially residual CRS-207, subjects will be administered antibiotics at the 
EOT visit and prior to receiving subsequent cancer-related therapy. 
 
 
 
 
 
 
 
 
 
Consult the package inserts for amoxicillin, trimethoprim, and sulfamethoxazole for product 
information on dosage and administration, contraindications, warnings/precautions, adverse 
reactions, and drug interactions. 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.3.7 
Concomitant Medications and Procedures 
Subjects may receive concomitant medications as required, unless specifically restricted or 
prohibited in this study (Section 7.3.8). Minor procedures such as dental work, skin biopsy, 
celiac plexus block, biliary stents, mediport/port insertion, and video-assisted thoracic surgery 
biopsy are allowed; however, CRS-207 should not be administered within 14 days of the 
procedure or until the investigator determines there is no additional risk to the subject. 
During the course of the study, subjects are anticipated to continue the use of prescribed 
medications identified during the screening procedures, consistent with study inclusion and 
exclusion criteria.  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
48 
Concomitant medications used in this study include: 
• Acetaminophen (paracetamol) prior to each CRS-207 infusion 
• Antiemetics according to American Society for Clinical Oncology guidelines (Basch, 
2011) 
• Antipyretics to treat fever or to prevent recurrence of fever post-CRS-207 infusion 
• IV narcotics such as morphine or meperidine (per institutional policy) for rigors 
associated with CRS-207 dosing 
• 
 
7.3.8 
Prohibited Medications and Procedures 
A subject may be removed from the study for use of prohibited medications or procedures. 
Approval must be obtained from the Medical Monitor for a subject to continue dosing if a 
prohibited medication is administered within the specified timeframes. The following therapies 
are not permitted or restricted during the study: 
• Non-study chemotherapy or immunotherapy (approved or investigational) 
• TNF pathway inhibitors or PI3 kinase inhibitors 
• Palliative radiation 
• Live vaccines (examples of live vaccines include, but are not limited to: measles, mumps, 
rubella, chicken pox, yellow fever, rabies, BCG, and typhoid [oral] vaccine). Seasonal 
influenza vaccines for injection are generally killed virus vaccines and are allowed. 
However, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and 
are not allowed. 
• Any major surgery or surgical procedure; if required must be discussed with the Medical 
Monitor to determine if it is appropriate for the subject to continue study treatment 
• Any other investigational product 
If a subject requires an emergent implant of a prohibited device while on therapy, the subject will 
receive a 14-day IV antibiotic regimen (see Section 7.3.6.1). 
In addition, the following medications are only restricted prior to and after CRS-207 infusions as 
indicated: 
• Systemically active steroids for more than 3 days or use of any systemic steroids within 
14 days before or after CRS-207 infusion, with the exception of inhaled steroids 
• Filgrastim (granulocyte colony stimulating factor; G-CSF) or sargramostim (granulocyte-
macrophage colony stimulating factor; GM-CSF) within 14 days prior to or 14 days after 
CRS-207 infusion  
• Prophylactic vaccines (e.g. pneumococcal vaccine, influenza vaccine) within 14 days 
prior to or after CRS-207 infusion 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
49 
The following therapies should not be administered during the study unless medically necessary; 
approval must be obtained from the Medical Monitor for a subject to continue dosing if therapy 
is given concurrently with study participation: 
• General anesthesia or deep sedation 
• Aspirin >325 mg/day 
• Acetaminophen > 4 g/day 
• Systemic antibiotics 
There are no prohibited therapies during the Follow-up Period. 
If subjects receive immunosuppressive medications on or after study, prophylactic antibiotics to 
prevent CRS-207 infection are strongly recommended for the duration of the treatment with the 
immunosuppressant (recommended oral 80 mg trimethoprim / 400 mg sulfamethoxazole once 
daily or 160 mg trimethoprim / 800 mg sulfamethoxazole (DS) three days a week). 
7.3.9 
Treatment Compliance 
Study treatments will be administered by IV infusion by a qualified health care professional at an 
approved study site. The date, time, and volume of each dose of study drug administered to each 
subject must be recorded in the dispensing log for the study and the eCRF.  
Antibiotics will be provided to subjects following the last dose of CRS-207 as indicated in Table 
2-1 or Table 2-2. Site personnel will contact the subject to confirm compliance with antibiotic 
treatment; subjects will be required to record self-administration of antibiotics in a diary. 
7.4 
Study Assessments and Procedures 
Screening assessments will be conducted to confirm eligibility and to obtain baseline 
measurements; screening must be completed within 28 days prior to first dose of study drug. An 
enrollment form will confirm subject eligibility after completion of all screening procedures. 
Subjects must initiate dosing of study drugs within 2 weeks of completed enrollment.  
The Treatment Period consists of multiple clinic visits during the initial four dosing cycles 
followed by treatment continuation, and an EOT visit.  
The Follow-up Period begins when subject has discontinued/completed treatment and completed 
the EOT visit. The subject will be contacted every 3 months during the Follow-up Period to 
obtain information on any subsequent cancer-related treatments and/or survival.  
All study visits (and visit windows), assessments, and procedures will be performed as indicated 
in the Schedule of Events (Table 2-1 or Table 2-2). Further details of study procedures and 
assessments can be found in the Study Reference Manual.  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
50 
7.4.1 
General Assessments  
7.4.1.1 
Informed Consent 
Before screening assessments are conducted, an individual must be given a complete explanation 
of the purpose and requirements of the study; an informed consent form (ICF) approved by the 
Institutional Review Board (IRB)/Ethics Committees (EC) and an authorization for use and 
disclosure of protected health information must be signed before any study-specific procedure is 
performed. However, assessments done as part of standard of care prior to informed consent may 
be used if they are within the required Screening Period. An original signed consent form will be 
retained in the subject’s source documentation at the site; a copy will be provided to the subject.  
7.4.1.2 
Eligibility  
Potential subjects will be evaluated for entry into the study according to the stated inclusion and 
exclusion criteria (Section 7.2). Individuals deemed ineligible for study enrollment do not need 
to complete all screening procedures. The reason for ineligible status will be documented. Tests 
with results that fail eligibility requirements may be repeated once during the Screening Period if 
the Investigator believes the results to be in error. Additionally, a subject who fails screening 
may repeat the screening process 1 time if the Investigator believes there has been a change in 
eligibility status (e.g. after recovery from an infection). 
For subjects who meet all inclusion/exclusion criteria, an enrollment form will be completed and 
sent to Sponsor or designee for review and approval. All screening assessments must be 
completed within a 3-week period; treatment must be initiated within 2 weeks of approved 
enrollment. 
7.4.1.3 
Demographics, Medical History, and Height 
Demographic data and a complete medical history will be collected at screening by the 
Investigator or qualified designee. Demographic information (as allowed by local regulations) 
will include date of birth, age, gender, ethnicity, and race. Medical history should include all 
active conditions and any condition considered to be clinically significant by the Investigator. 
Medical and surgical history, and concurrent illnesses will be coded using the National Cancer 
Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.03. Details regarding the 
disease for which the subject has enrolled in this study (e.g. date of diagnosis, primary tumor 
histology, prior surgery(ies), radiation therapy, and stage of cancer) will be recorded. 
Height (without shoes) will be obtained at screening with a stadiometer. Body mass index will be 
derived using height and weight. 
7.4.1.4 
Archived Tumor Tissue and Tumor Biopsies 
Archived tumor tissue (paraffin embedded block or unstained charged slides) will be collected (if 
available) and may be used for analysis to confirm predominantly epithelial histology. Archived 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
51 
samples should be submitted with a pathology report; personal identifying information must be 
redacted.  
An image assisted core needle biopsy using standard techniques will be obtained from the 
primary tumor site(s) and/or accessible metastatic lesions 1) at screening (baseline) and 2) a 
paired biopsy during treatment (Cycle 2 Day 15 post CRS-207 and pembrolizumab 
administration). An additional biopsy may be requested at the time of disease progression (EOT 
visit). The Cycle 2 Day 15 biopsy should not be collected until at least 7 days have passed since 
CRS-207 administration, but no later than Day 15 of cycle to allow sufficient recovery time prior 
to next CRS-207 administration. The tissue sample should have proper size to enable IHC 
analysis of PD-L1. Fine needle aspirations will not be acceptable. If a subject’s tumor is thought 
to be unsafe for biopsy by the Investigator, the site must discuss with the Medical Monitor prior 
to enrollment in study. If additional biopsies or relevant samples (e.g. pleural fluid) are collected 
for routine care during course of study, a sample should be retained if possible for Sponsor 
research evaluation. Detailed instructions for tissue collection, processing and shipment are 
provided in the Laboratory Manual.  
Paired tumor biopsies and archival tissue will be analyzed for PD-L1 expression as well as other 
immune checkpoint molecules and infiltration of immune cells (e.g. T cell, myeloid and DC 
subpopulations) by IHC and gene expression profiling. PD-L1 expression may predict response 
to anti-PD-1 (Topalian, 2012; Brahmer, 2010). PD-L1 is also upregulated in response to IFN-γ 
released by infiltrating T cells and could potentially be a predictor of response to any active 
immunotherapy.  Characterization of immune checkpoint expression as well as immune 
infiltrates may be predictive of response to therapy and may also give insight into next 
generation combinatorial approaches. 
7.4.2 
Efficacy Measures 
Efficacy will be evaluated by changes in tumor burden, pulmonary function, and survival. The 
assessments that will be performed throughout the study to derive primary, secondary, and 
exploratory efficacy variables are described below and will be conducted according to the 
Schedule of Events in Table 2-1 or Table 2-2. Efficacy endpoints and associated analyses are 
described in Section 7.5.5.  
7.4.2.1 
Tumor Imaging and Response Assessments 
CT scans of the thorax and abdomen will be performed at screening (pre-treatment baseline 
assessment) and up to 7 days prior to dosing every other cycle starting at Cycle 3 and throughout 
the Treatment Period. If CT scan is contraindicated (e.g. allergy to contrast dye), a MRI should 
be performed. Subjects with previously treated brain metastases must have a brain CT scan done 
within 14 days prior to first dose of study drug to confirm negative for new brain metastases. 
Radiographic tumor evaluation should include CT of all affected sites. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
52 
For each scan, tumor measurements should be obtained using modified RECIST for MPM and 
assessment of response will be determined by the local Investigator. The method of assessment 
and technique should be consistent throughout the study to enable characterization of each 
identified and reported lesion.  
If radiographic disease progression is observed, another scan should be done at least four weeks 
later to confirm disease progression prior to treatment discontinuation. If a subject discontinues 
treatment without progressive disease (PD), Evaluation Visits with CT scan/tumor assessments 
should be completed every 6 weeks until documented disease progression. 
Additional supportive analyses may be performed separately by an independent reviewer using 
objective disease responses definitions based on RECIST v1.1 and/or immune related response 
criteria (irRC).  Sites must submit a copy of each scan on CD or other image media to the 
Sponsor; all protected health information (e.g. name, medical record number, etc.) must be 
redacted.  Additional instructions for submission of scans are located in the Study Reference 
Manual. 
7.4.2.2 
Pulmonary Function Testing 
Spirometry will be administered in accordance with American Thoracic Society and European 
Respiratory Society taskforce guidelines (Miller, Crapo, , 2005; Miller, Hankinson, , 2005) to 
assess pulmonary function. Spirometry will be performed with equipment at the study site; 
spirometry guidelines are provided in the Study Reference Manual. FVC is the pulmonary 
function variable. The percent predicted values will be calculated using published normative data 
(Hankinson, 1999) using height obtained at screening. 
7.4.2.3 
Survival Follow-Up 
Following the Treatment Period, subjects will be contacted at 3 months intervals to assess 
survival and subsequent cancer-related therapies. Follow-up will continue until death of the 
subject, loss to follow-up, or close of study by the Sponsor. For subjects who withdraw from the 
study prior to completion of the Follow-up Period, reasonable efforts will be made to collect 
survival outcome. Sites will attempt to obtain vital status data from public records or other 
external sources where possible if a subject withdraws consent from study (i.e. refuse follow-up 
for vital status) or is documented as lost to follow up. All deaths must be reported on the eCRF.  
The Sponsor may request survival status be assessed at additional time points during the course 
of the study. These additional contacts may be requested for safety review, interim analysis, 
and/or final analysis. All subjects who are not known to have died prior to the request for these 
additional survival status time points will be contacted at that time. 
7.4.3 
Safety Assessments 
Safety assessments will be performed to characterize the safety of CRS-207 and pembrolizumab 
use in MPM. Safety will be assessed by collection of data on AEs, clinical laboratory 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
53 
assessments, ECOG performance status, vital signs, weight, physical examination, 
electrocardiogram (ECG) parameters, and concomitant medications. Clinically significant 
changes from pre-treatment values in safety assessments should be reported as AEs. Safety 
assessments described below will be conducted according to the Schedule of Events (Table 2-1 
or Table 2-2).  
7.4.3.1 
Eastern Cooperative Oncology Group Scale of Performance Status 
The ECOG Scale of Performance Status is recognized as a standard tool to measure disease 
impact on daily living activities (Oken, 1982). The ECOG scale will be used by site personnel to 
determine eligibility and characterize a subject’s level of functioning (self-care, daily activity, 
and basic physical ability) as indicated throughout the Treatment Period. 
7.4.3.2 
Vital Signs and Pulse Oximetry 
Vital signs, including blood pressure, pulse rate, respiratory rate, and temperature and pulse 
oximetry will be performed at each indicated study visit. Vital signs will be obtained prior to, 
and immediately following each pembrolizumab infusion. Vital signs will be obtained prior to, 
every 30 minutes during the CRS-207 infusion and every hour during post-infusion follow-up. 
Subjects will be observed for at least 4 hours after the first CRS-207 infusion and the first cycle 
with same day dosing and at least 2 hours for each subsequent infusion. Pulse oximetry may be 
performed as clinically indicated. 
Any clinically significant abnormal findings in vital signs or pulse oximetry should be recorded 
as an AE. 
7.4.3.3 
Physical Examination and Weight 
Comprehensive Physical Examination 
Complete physical examinations will be conducted at screening and EOT. Comprehensive 
physical examinations must be performed by a medically qualified individual such as a licensed 
Physician, Physician's Assistant, or an advanced Registered Nurse Practitioner, as local law 
permits. The comprehensive physical examination will include the following organ or body 
system assessments: skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular 
system; abdomen (liver and spleen); extremities; lymph nodes; and a brief neurological 
examination. Before the first dose of study drug, clinically significant abnormal findings should 
be recorded as medical history. After the first dose of study treatment, new clinically significant 
abnormal findings should be recorded as AEs. 
Symptom-directed Physical Examination 
Symptom-directed physical examinations will be conducted at all other indicated visits (up to 3 
days prior to dosing). The Investigator or medically qualified designee will perform a symptom-
directed evaluation as clinically indicated. The targeted physical examination will include 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
54 
assessment(s) of the body systems or organs, as indicated by subject symptoms, AEs, or other 
findings. New clinically significant abnormal findings should be recorded as AEs. 
Weight will be obtained at each indicated visit, and prior to receiving any study drug.  Any 
clinically significant abnormal findings in weight should be recorded as an AE 
7.4.3.4 
Adverse Events 
AEs will be recorded from the time of first study drug administration until 28 days following the 
last dose of study drug or initiation of subsequent cancer-related therapy, whichever occurs first. 
If the EOT visit occurs less than 28 days from the last dose of study drug, the subject will be 
contacted 28 days (- 3 days) after the date of last study drug administration to complete the AE 
reporting period. A clinic visit or follow-up contact for AEs will also be conducted 1 day after 
each CRS-207 infusion (and one day after pembrolizumab infusions during cycles where CRS-
207 is not administered). Contact must be documented in the study records. 
All AEs and abnormal clinical laboratory assessments will be assessed for severity using the 
NCI-CTCAE v. 4.03. The determination, evaluation, reporting, and follow-up of AEs will be 
performed as outlined in Section 8. 
7.4.3.5 
Concomitant Medications 
Medications used within 28 days prior to first dose of study medication will be recorded.  A 
clinic visit or follow-up contact for concomitant medications will also be conducted 1 day after 
each CRS-207 infusion (and one day after pembrolizumab infusions during cycles where CRS-
207 is not administered). All concomitant medication administered from Cycle 1 until the EOT 
visit will be recorded in the eCRF (including pre-medications and all over the counter 
medications). The generic name, dosage, duration, and reason for the concomitant medication 
should be included. Changes in the use of concomitant medications will be captured at each 
study visit. 
7.4.3.6 
Electrocardiogram 
At indicated visits routine 12-lead ECGs will be performed.  ECGs should be performed after the 
subject has rested for ≥5 minutes. For consecutive-day dosing, ECGs will be performed prior to 
each dose of study medication, immediately after the infusion, and at 1-hour post infusion. For 
visits where pembrolizumab and CRS-207 are administered on the same day, routine 12-lead 
ECGs will be performed prior to pembrolizumab infusion, immediately after pembrolizumab 
infusion, immediately after CRS-207 infusion, and at 1-hour post CRS-207 infusion. If abnormal 
at 1-hour post-infusion, repeat until baseline achieved. Additional ECGs may be performed if 
clinically indicated.   
ECG parameters include heart rate, PR interval, QT interval, QRS duration, QTcF (Fridericia's 
correction), and QTcB (Bazett's correction). The ECG will be interpreted by the Investigator as 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
55 
normal, not clinically significant abnormal, and clinically significant abnormal results. Clinically 
significant abnormal findings should be recorded as an AE.  
7.4.3.7 
Clinical Laboratory Evaluation for Safety 
Routine hematology, serum chemistry, and urinalysis will be performed as a safety measure and 
to confirm dosing eligibility throughout the study (Section 7.4.4.2). The clinical significance of 
laboratory parameter findings will be determined by the Investigator throughout the study. The 
Medical Monitor may, depending on study criteria, be consulted before enrollment about a 
potential subject with abnormal laboratory values that are not considered clinically significant. 
Clinically significant abnormal laboratory values occurring during the clinical study will be 
followed until repeat tests return to normal, stabilize, or are no longer clinically significant. All 
abnormal laboratory values considered clinically significant by the Investigator must be recorded 
in the AE page of the eCRF. Any abnormal test that is determined to be an error does not require 
reporting as an AE. 
7.4.4 
Laboratory Assessments 
A panel of laboratory assessments on blood and urine samples will be used to characterize the 
study population, and assess efficacy and safety throughout the Treatment Period. Assessments 
will be conducted per the appropriate Schedule of Events (Table 2-1 or Table 2-2). 
7.4.4.1 
Screening/Baseline-specific Laboratory Assessments 
Blood samples will be obtained at screening to confirm eligibility and characterize immune 
status and prognostic tumor biomarkers for each subject and the study population. These initial 
laboratory assessments may be conducted at the institution’s local laboratory and include:   
• Virology screen for HIV antibody, hepatitis B surface antigen, and hepatitis C antibody 
o Hepatitis C viral load (if indicated) 
7.4.4.2 
Safety Laboratory Assessments 
Routine hematology, serum chemistry, thyroid function tests, coagulation panels, and urinalysis 
will be conducted as a measure of safety and dosing eligibility per protocol requirements 
(Section 7.2.3). All clinical laboratory evaluations will be performed by the institution’s local 
laboratory. Testing may be completed up to 3 days prior to each study drug administration. 
Fasting is not required. Additional tests may be performed if clinically indicated. 
The following parameters will be evaluated at Screening and throughout the Treatment Period as 
indicated: 
• Hematology:  complete blood count (WBC, red blood cells, hematocrit, and hemoglobin) 
with differential including ANC, ALC and platelet count 
• Serum chemistry:  sodium, potassium, chloride, bicarbonate, glucose, blood urea 
nitrogen, creatinine, lactate dehydrogenase, ALT, AST, alkaline phosphatase, bilirubin 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
56 
(total, direct, indirect), total protein, albumin, calcium, magnesium, uric acid, and 
phosphate 
• Coagulation panel: PT, INR, aPTT, D-dimers, fibrinogen 
• Thyroid panel: triiodothyronine (T3) or free triiodothyronine (FT3), free thyroxine (FT4), 
and thyroid stimulating hormone (TSH) 
• Urinalysis: bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, protein, and specific 
gravity (includes microscopy at Screening and EOT)  
Pregnancy Testing and Contraception 
The effects of CRS-207 and pembrolizumab on a fetus in utero or on the composition of sperm 
are unknown. Therefore WOCBP and fertile males must consent to use highly effective 
contraception [per (CTFG, 2014)] throughout the Treatment Period (or for 120 days after their 
final dose of study drug). Contraception must include at least one barrier method to minimize 
risk of fluid transmission. 
A WOCBP is defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. 
Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 years in 
the absence of other biological or physiological causes. For study eligibility, WOCBP must have 
negative pregnancy tests at screening and within 24 hours of first study drug administration. A 
serum pregnancy test (HCG) is required at screening; at all other indicated visits, only a urine 
pregnancy test is required. If a urine pregnancy test is positive, the results should be confirmed 
with a serum pregnancy test. Pregnancy of a subject or partner must be reported and followed 
(Section 8.4).  
7.4.4.3 
Blood for CRS-207 Surveillance 
Blood samples will be collected from subject’s peripheral vein and from the central line port, if 
applicable, at the EOT visit (prior to initiation of antibiotics) and at all visits indicated after EOT 
to monitor for presence of CRS-207. Subjects with samples positive for the presence of CRS-207 
will be re-tested until negative results are confirmed. 
7.4.4.4 
Biomarker and Research Laboratory Assessments  
Research assessments will be conducted on blood samples and tumor tissues and may help to 
characterize and monitor baseline and post-treatment immune responses mediated by CRS-207 
and pembrolizumab. Samples required for laboratory evaluations will be collected and processed 
by sites as outlined in the Laboratory Manual. All analyses will be conducted by the Sponsor or 
the Sponsor’s designee.  
Exploratory assessments may include:  
• Total CD4 and CD8 counts (will be done at Central Laboratory) 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
57 
• Human leukocyte antigen (HLA) typing (type A and B of MHC Class I antigens; low 
resolution) 
• Characterization of treatment induced immune responses including T cell responses to 
Lm and mesothelin,  
• Immune cellular phenotyping and functional analyses of peripheral blood mononuclear 
cells (PBMCs) and tumor infiltrating lymphocytes 
• Tumor biomarkers or prognostic factors (e.g. PD-1, mesothelin, plasma osteopontin, etc.) 
• Circulating cytokines, chemokines, miRNA and other proteins. 
• Gene expression profiling of PBMCs 
• T cell receptor (TCR) profiling of PBMCs and tumors 
Specific testing may include analysis for changes in protein analytes such as cytokines, 
antibodies, relevant tumor markers and markers of immune function by enzyme-linked 
immunosorbent assay (ELISA), or other relevant methods including peptide or protein arrays. In 
addition, assays of immune cell phenotyping and functions or responses may be conducted using 
whole blood samples and PBMCs. To explore whether a diverse T cell repertoire is predictive of 
response to therapy, sequencing of TCR genes may be performed on DNA isolated from 
peripheral blood and tumor to quantitate the composition of the T cell repertoire prior to and 
during therapy. Genetic markers associated with response or resistance may also be measured 
using peripheral blood DNA; peripheral blood DNA may also be used as a germline control to 
compare with tumor cell DNA. RNA isolated from peripheral blood for gene expression analysis 
may be used to characterize subjects who respond or are resistant to treatment. Additional 
assessments and methodologies may be used at the Sponsor’s discretion. 
7.4.5 
Subset Studies 
7.4.5.1 
CRS-207 Shedding and Clearance Subset 
A subset of 10 subjects from select sites in the US will undergo assessment of CRS-207 shedding 
and clearance as indicated in Table 2-1 or Table 2-2. Urine, rectal swab, and throat swab samples 
will be obtained pre-CRS-207, 4 hours (± 30 minutes) after the end of CRS-207 infusion, and 18-
24 hours, and 7 days post-CRS-207 infusion. Clearance of CRS-207 in blood will be assessed 
pre-dose, and 18-24 hours, and 7 days post-CRS-207 infusion. Subjects with samples positive for 
the presence of CRS-207 will be re-tested until negative results are confirmed. 
7.4.6 
Appropriateness of Measures 
Tumor imaging is the gold standard for assessing monitoring disease progression and tumor 
response in patients with cancer. The primary efficacy variable, ORR, is an accepted surrogate of 
efficacy appropriate for use in single-arm studies with smaller sample sizes. Tumor response will 
be evaluated using modified RECIST. Modified RECIST criteria for MPM was adapted to the 
growth pattern of MPM and has been shown to correlate with survival and lung function and is 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
58 
used to measure outcomes (Byrne and Nowak, 2004). Immunotherapeutic agents such as 
pembrolizumab may produce antitumor effects by potentiating endogenous cancer-specific 
immune responses. The response patterns seen with such an approach may extend beyond the 
typical time course of responses seen with cytotoxic agents, and can manifest a clinical response 
after an initial increase in tumor burden or even the appearance of new lesions, therefore 
radiologic disease progression should be confirmed by another scan at least 4 weeks after the 
initial scan and prior to discontinuing study drug.   
Additional secondary efficacy variables will also be derived from tumor imaging and response 
assessments. Pulmonary function is compromised in patients with MPM; spirometry is routinely 
used to assess pulmonary function variables in this patient population. OS is the universally 
accepted direct measure of benefit and is an objective measure, although may be limited by 
difficulties with patient follow-up in smaller studies and confounded by non-cancer deaths in 
long-term studies.  
The safety parameters to be evaluated in this study include standard assessments such as 
recording of medical history, AEs and SAEs, physical examination, vital signs, ECGs, serum 
chemistry and hematology, urinalysis, concomitant medications, and other routine clinical and 
laboratory procedures. 
7.5 
Statistical Analysis 
The completeness of the data affects the integrity and accuracy of the final study analysis.  
Therefore, efforts will be made to ensure complete, accurate and timely data collection, and to 
avoid missing data. The procedures for handling missing, unused, or spurious data, along with 
the detailed method for analysis of each variable, transformations, and exploratory analyses will 
be presented in the Statistical Analysis Plan (SAP); the information below is intended as a guide 
to planned analyses.  
7.5.1 
Sample Size Determination 
The sample size is based on an A’Hern single-stage phase 2 design (A'Hern, 2001). A sample 
size of 35 evaluable subjects are required to decide whether the proportion responding is less 
than or equal to 0.21 or greater than or equal to 0.40. If the number of responses is 12 or more, 
the hypothesis that P <= 0.21 is rejected with a target error rate of 0.05 (alpha). If the number of 
responses is 11 or less, the hypothesis that P >= 0.40 is rejected with a target error rate of 0.20 
(power = 0.80). 
The estimate of ORR from historical controls is based on a review of published literature, where 
Investigator-assessed response rates from 24% (Alley, 2015) to 28% (Quispel-Janssen, 2016) 
were reported. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
59 
7.5.2 
General Considerations 
All statements of statistical significance will be based on an overall two-tailed test at the 0.05 
level of significance unless otherwise stated. Descriptive and inferential statistical methods will 
be used to summarize data. The term “descriptive statistics” refers to the number of subjects (n), 
mean, median, standard deviation, minimum, and maximum for continuous variables, and refers 
to the number and/or percentage of subjects (or events) for categorical variables. Summaries of 
time to event data from Kaplan Meier estimates will include the number of events, number of 
censored subjects, median and 95% confidence intervals.  
All statistical analyses will be performed using SAS. The effects of noncompliance, dropouts, 
and covariates will be assessed to determine the impact on the general applicability of results 
from this study.  
7.5.3 
Subject Information 
Subject disposition summaries will include the number of enrolled subjects, the number of 
subjects receiving study drug, the number of subjects completing the study, the number of 
subjects withdrawing prematurely, and the reasons for discontinuation. 
Demographics and baseline disease characteristics will be summarized using descriptive 
statistics. 
7.5.4 
Analysis Sets 
Evaluable Analysis Set (EAS) is defined as all subjects who received at least 1 dose of study 
treatment and were either assessed for response or were discontinued due to toxicity or clinical 
progression (or death due to clinical progression). The EAS will be used for analyses of the 
primary and secondary efficacy endpoints utilizing clinical response. 
Full Analysis Set (FAS) is defined as all subjects who received at least 1 dose of study 
treatment. The FAS will be used for other analyses of efficacy (including pulmonary function 
and OS). 
Safety Set includes all subjects who received any study treatment. All analyses of safety data will 
be conducted using the safety set. 
Additional analysis sets (e.g. per protocol set) may be defined in the SAP. 
7.5.5 
Efficacy Analyses 
All primary and secondary efficacy variables derived from tumor imaging and response 
assessments will be determined by the local Investigator using modified RECIST guidelines for 
MPM. Additional supportive analyses may be performed separately by an independent reviewer 
using objective disease responses definitions based on RECIST v1.1 and/or irRC. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
60 
7.5.5.1 
Primary Efficacy Variable and Analysis 
For the primary efficacy analysis, ORR is defined as the proportion of subjects with PR or CR 
according to modified RECIST for MPM.  Subjects who discontinue due to toxicity or clinical 
progression prior to post-baseline tumor assessments will be considered as non-responders. 
Subjects who discontinue for other reasons prior to post-baseline tumor assessments will be 
replaced and not included in the primary efficacy analysis. 
7.5.5.2 
Secondary Efficacy Variables and Analyses 
Secondary efficacy variables will be calculated for all subjects who receive at least one dose of 
study drug and are evaluable for response. 
Secondary efficacy variables in the study include: 
Disease control rate (DCR) defined as the percentage of subjects with CR, PR, or SD. Subjects 
who discontinue prior to post-baseline tumor assessments will be considered as non-responders. 
Progression-free survival (PFS) is defined as the time from first dose of study drug until first 
documentation of disease progression or death due to any cause.  
Subjects who do not experience disease progression and are alive on or before the data cut-off 
date will be censored at the time of last tumor assessment or data cut-off date, whichever is 
earlier. Subjects who do not experience disease progression and start new systemic anti-cancer 
therapy will be censored at the time the new systemic anti-cancer therapy was begun or the data 
cut-off date, whichever is earlier. Subjects with no assessments of disease progression will be 
censored at the time of receipt of first study drug. Subjects who are lost to follow-up for 
assessment of disease progression will be censored at their last tumor assessment or data cut-off 
date, whichever is earlier.  
Pulmonary function improvement is defined as an increase in FVC from baseline of either ≥400 
mL or ≥ 20%, assessed using spirometry.  
The analysis of pulmonary function response will be based on the percent of subjects with 
documented improvement in pulmonary function variables. Assessments obtained after a switch 
to another anti-cancer therapy will be excluded from the analysis. Subjects who discontinue prior 
to post-baseline assessments will be considered non-responders.  
Overall Survival (OS) defined as the time from first dose of study drug until date of death due to 
any cause. Subjects without documentation of death at the time of analysis will be censored as of 
the date the subject was last known to be alive, or the data cut-off date, whichever is earlier. 
OS will be summarized using Kaplan-Meier estimates. 
7.5.5.3 
Other Efficacy Variables and Analysis 
Additional efficacy analyses will be evaluated based on the following additional variables: 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
61 
• Best Overall Response (BOR) defined as the subject’s best objective disease response 
across all evaluable on-treatment assessments from all courses until another anti-cancer 
therapy has been introduced.  
• Objective tumor response over time, and duration of response (DOR) defined as the time 
from first PR or CR until PD or death. DOR is defined as the time from the first tumor 
assessment that supports the subject’s objective disease response to the time of disease 
progression or death due to any cause. 
• Change from baseline in pulmonary function tests (FVC) 
Exploratory analyses of the data will be conducted as deemed appropriate. Details of additional 
analysis of other variables are provided in the SAP. 
7.5.6 
Safety Analyses 
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) 
version 18.1 or higher and assessed for severity using the NCI-CTCAE v. 4.03. AEs will be 
summarized by system organ class and preferred term and presented in decreasing order of 
frequency. 
Changes in clinical laboratory assessments, ECOG performance status, vital signs, weight, 
physical examination, ECG, and concomitant medications parameters from baseline to the EOT 
will be examined. Treatment-emergent changes from normal to abnormal values in key 
laboratory parameters will be identified. Laboratory data will be summarized for each time-point 
that specimens are collected. Changes in NCI toxicity grading will be presented using shift tables 
and listings of clinically significant values. 
7.5.7 
Research Laboratory Analyses 
Analyses of research laboratory samples, tumor biopsies, and immune response data will be 
described separately outside the context of the SAP. 
7.5.8 
Timing of Analysis 
The primary analysis will be performed following completion of enrollment and response 
assessments in the first 35 evaluable subjects. Information on survival will continue to be 
gathered and may be used for supplementary analyses after the completion of the final study 
report. 
7.5.9 
Data Monitoring Committee 
There will be no formal Data Monitoring Committee for this study. Safety data including all 
unacceptable toxicities will be reviewed by a Safety Review Team comprised of participating 
investigators in the study, the Medical Monitor, and representatives of the Sponsor. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
62 
8 
ADVERSE EVENT REPORTING  
8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can therefore be any unfavorable and/or 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational medicinal product, whether or not related to the 
investigational medicinal product. All AEs, including observed or volunteered problems, 
complaints, or symptoms, are to be recorded on the appropriate eCRF. 
AEs, which include clinical laboratory test variables, occurring from the time of first study drug 
administration and up to 28 days after the last dose of study drug, whether observed by the 
Investigator or reported by the subject will be monitored and documented on the AE eCRF. 
Subjects should be instructed to report any AE that they experience to the Investigator. At each 
indicated visit, Investigators should make an assessment for AEs and record the event on the 
appropriate AE eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (e.g. surgery, endoscopy, tooth 
extraction, or transfusion) should be recorded as an AE, not the procedure.  
Progression of the cancer under study is not considered an AE in this study. The term "disease 
progression" should be recorded as an AE/SAE only if there are no other identifiable AEs/SAEs 
associated with the disease progression at the time of reporting. For events associated with 
disease progression, the relevant signs and symptoms should be reported using a diagnosis 
whenever possible rather than individual underlying signs and symptoms. When a clear 
diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. If the 
events resulting from disease progression meet the criteria for an SAE (e.g. resulted in 
hospitalization, a life-threatening event, or death), the specific event(s) should be reported as an 
SAE(s). In both cases (i.e. AEs or SAEs related to disease progression), it should be indicated 
that each event (reported as a diagnosis or as signs and symptoms) is related to disease 
progression on the AE CRF. 
Any medical condition already present prior to the first dose of study drug should be reported in 
medical history unless the medical condition or signs or symptoms present at baseline change in 
severity or seriousness at any time during the study. In this case, it should be reported as an AE. 
Clinically significant abnormal laboratory or other examination (e.g. ECG) findings that are 
detected during the study or are present at screening and significantly worsen during the study 
should be reported as AEs. The Investigator will exercise his or her medical and scientific 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
63 
judgment in deciding whether an abnormal laboratory finding or other abnormal assessment is 
clinically significant. Clinically significant abnormal laboratory values occurring during the 
clinical study will be followed until repeat tests return to normal, stabilize, or are no longer 
clinically significant. Any abnormal test that is determined to be an error does not require 
reporting as an AE. 
Examples of AEs include the following: 
• Significant or unexpected worsening or exacerbation of the indication under study 
• Exacerbation of a chronic or intermittent preexisting condition, including an increase in 
frequency or intensity of the condition 
• New conditions detected or diagnosed after investigational agent administration even if they 
were present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected interaction with another medical 
product 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational 
agent or a concurrent medication. 
• For CRS-207: an overdose should not be reported as an AE or SAE; instead, the 
symptoms resulting from the overdose should be reported as the AE or SAE. 
Examples of AEs do not include the following: 
• Medical or surgical procedures (e.g. endoscopy, appendectomy); instead, the medical 
condition that led to the procedure is an AE 
• Situations that are unwanted but in which an untoward medical occurrence did not occur 
(e.g. social inconvenience after admission to a hospital) 
• Anticipated day-to-day fluctuations of a pre-existing disease or condition (present or detected 
before enrollment) that does not worsen overall 
A follow-up is required for all subjects with AEs until the event has been resolved or the 
condition has stabilized. In case of unresolved AEs, including significant abnormal laboratory 
values at the EOT visit assessment, these events will be followed up until resolution or until they 
become clinically not relevant. 
8.1.1 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE and the potential relationship 
between the AE and the study medication. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
64 
Assessment of Severity: 
The severity of all AEs should be graded according to the NCI-CTCAE v. 4.03 
(http://ctep.cancer.gov/reporting/ctc.html). For AEs not listed in the CTCAE, the following 
grading system should be used: 
• Mild (CTCAE Grade 1): Transient symptoms, awareness of sign/symptom, but easily 
tolerated and no interference with subject’s daily activities 
• Moderate (CTCAE Grade 2): Marked signs/symptoms that interfere with subject’s usual 
activities, but still acceptable 
• Severe (CTCAE Grade 3): Incapacitating signs/symptoms which cause considerable 
interference with the subject’s daily activities, unacceptable 
• Life-threatening (CTCAE Grade 4): Life-threatening or disabling AE 
• Death (CTCAE Grade 5): Death-related AE 
 
Attribution: 
The Investigator is obligated to estimate the relationship between the investigational agents and 
the occurrence of each AE or SAE using best clinical judgment. Other causes, such as the 
underlying disease, concomitant therapy, other risk factors, and the temporal relationship of the 
event to one or both of the investigational agents should be considered and investigated. The 
Investigator should consult the IB or product labeling information for marketed products in the 
determination of the assessment. The Investigator should consider all possible etiologies for the 
AE and render a causality assessment based on the most likely contributing factor to the AE. 
There may be situations when an SAE has occurred and the Investigator has minimal information 
to include in the initial report. However, the Investigator must assess causality for every event 
before the transmission of the SAE. The Investigator may change his or her opinion of the 
causality in light of follow-up information, amending the SAE report.  
The assessment of the relationship between the AE and the study medication will be determined 
using one of the following attribution categories as outlined in the NCI Guidelines: Adverse 
Event Reporting Requirements (2013).   
RELATIONSHIP 
ATTRIBUTION 
DESCRIPTION 
Unrelated to investigational 
agent/intervention 
Unrelated 
The AE is clearly NOT related to the 
intervention 
Unlikely Related 
The AE is doubtfully related to the 
intervention 
Related to investigational 
agent/intervention 
Possibly Related 
The AE may be related to the intervention 
Probably Related 
The AE is likely related to the intervention 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
65 
RELATIONSHIP 
ATTRIBUTION 
DESCRIPTION 
Definitely Related 
The AE is clearly related to the 
intervention 
AEs listed as possibly, probably, or definitely related are considered to have a suspected 
“reasonable causal relationship” to the investigational agent/intervention (ICH E2A).  The 
expression "reasonable causal relationship" is meant to convey in general that there are facts 
(evidence) or arguments to suggest a causal relationship 
8.2 
Serious Adverse Events 
An AE or adverse reaction is considered serious if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening AE 
o NOTE: An AE or adverse reaction is considered “life-threatening” if, in view of 
either the Investigator or Sponsor, its occurrence places the subject at immediate 
risk of death. It does not include an event that, had it occurred in a more severe 
form, might have caused death. 
• Requires hospitalization or prolongation of existing hospitalizations; 
o NOTE: Any hospital admission with at least 1 overnight stay will be considered 
an inpatient hospitalization. An emergency room visit without hospital admission 
will not be recorded as an SAE under this criterion, nor will hospitalization for a 
procedure scheduled or planned before signing of informed consent. However, 
unexpected complications and/or prolongation of hospitalization that occur during 
elective surgery should be recorded as AEs and assessed for seriousness. 
Admission to the hospital for social or situational reasons (i.e. no place to stay, 
live too far away to come for hospital visits) or for observation post-study drug 
administration will not be considered a SAE.  
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect; or 
• An important medical event 
o NOTE: Important medical events that may not result in death, be life-threatening, 
or require hospitalization may be considered an SAE when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalizations, or the development of 
drug dependency. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
66 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
8.3.1 
Initial Reports 
SAEs will be collected from the time of first study drug administration through 90 days 
following cessation of treatment, or 28 days following cessation of treatment if the subject 
initiates new anticancer therapy, whichever is earlier.  SAEs and events of clinical interest must 
be reported to the Sponsor (or designee) within 24 hours of the knowledge of the occurrence. 
Outside of the 90-day period, only SAEs considered related to the administration of study drug 
must be reported to the Sponsor. 
In the event an SAE is observed or reported, the SAE report will be completed as thoroughly as 
possible including all available details about the event and the signature of the Investigator. If the 
Investigator does not have all information about an SAE, the Investigator will not wait to receive 
additional information before notifying the Sponsor of the event and completing the form. The 
form will be updated when additional information is received.  
The SAE form in the electronic data capture (EDC) system should be completed for each SAE. 
Upon completion, designated study personnel will be notified electronically and will retrieve the 
form. If the event meets serious criteria and it is not possible to access the EDC system, an email, 
telephone, or facsimile communication within 24 hours of awareness is acceptable. When the 
EDC system becomes available, the SAE information must be entered within 24 hours. 
8.3.2 
Safety Reporting Contact Information 
Safety contact information may be found in the Study Reference Manual. 
8.3.3 
Expedited Reporting Requirements 
The Sponsor (or designee) will report all SAEs that are unexpected and considered related to the 
administration of the investigational agent to the appropriate health and regulatory authorities 
and Investigators in the form of an expedited safety report within 15 calendar days after 
receiving information on the SAE. The Investigators will notify their reviewing IRB/EC and 
other committee(s) as required by institutional policies. 
The Sponsor will also report to the appropriate health and regulatory authorities by facsimile, e-
mail, or phone within 7 days of receiving the information, any unexpected life-threatening or 
fatal SAEs that are considered related to the investigational agent.  
8.3.4 
Follow-Up Reports 
The Investigator must continue to follow the subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
67 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
and submit any supporting documentation (e.g. subject discharge summary or autopsy reports) 
via fax or e-mail to the Sponsor or designee.  
8.4 
Events of Clinical Interest 
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported following SAE reporting procedures in Section 8.3. All ECIs must be 
reported for the duration of the study regardless of causality. 
Events of clinical interest for this trial include: 
• 
 
 
 
 
 
 
 
• An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of 
normal and an elevated total bilirubin lab value that is greater than or equal to 2X the 
upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less 
than 2X the upper limit of normal, as determined by way of protocol-specified laboratory 
testing or unscheduled laboratory testing. 
8.5 
Adverse Events of Special Interest 
Suspected infection with CRS-207 and/or Listeria are considered adverse events of special 
interest (AESI) and should be reported following SAE reporting procedures in Section 8.3. All 
AESIs must be reported for the duration of the study regardless of causality. 
In the event a subject has a positive Listeria test at any time during or after study participation 
(except within 7 days after a CRS-207 infusion), the event should be reported to the Sponsor 
within 24 hours of the event. 
8.5.1 
Confirmed Listeria Infection 
In the event a subject has a positive Listeria culture at any time during or after study participation 
(except within 7 days after a CRS-207 infusion), Sponsor should be notified within 24 hours of 
the event. 
If Listeria has been confirmed at the clinical site or an external laboratory, all efforts should be 
made to obtain and ship the bacterial isolate from the original positive culture to the Sponsor or 
designee for strain confirmation; records on all samples cultured during this period must be 
obtained and provided to the Sponsor.  Refer to the Laboratory Manual for shipping instructions. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
68 
8.5.2 
Suspected (Unconfirmed) Infection with CRS-207 or Listeria 
In the case of a suspected persistent CRS-207 or Listeria infection that has not been confirmed 
by culture, collection of blood, urine and stool samples in duplicate is recommended. One set of 
samples should be cultured locally for Listeria per institutional guidelines. Culture of 
cerebrospinal fluid should be obtained for subjects with suspected central nervous system 
infection. In such instances, analysis of cerebrospinal fluid should also include cell count, 
protein, glucose, and Gram stain. If samples are positive for Listeria, the Sponsor must be 
notified immediately, and the duplicate samples and positive listeria isolate must be sent to 
Sponsor or designee for strain confirmation. Instructions on collection, storage and shipping of 
samples for CRS-207 testing are provided in the Laboratory Manual.  
If infection with CRS-207 is confirmed or suspected, IV antibiotics (Section 7.3.6.1) should be 
initiated as soon as possible and follow-up samples obtained for testing periodically to confirm 
absence/clearance of any CRS-207 infection. The Medical Monitor should be consulted 
regarding continuation of study drug treatment and treatment of suspected or confirmed 
infection. 
 
8.6 
Pregnancy Reporting 
If the subject or partner of a subject participating in the study becomes pregnant during the study 
or within 120 days of discontinuing study drug (or 30 days if the subject initiates new anticancer 
therapy, whichever is earlier) the Investigator should report the pregnancy within 24 hours of 
being notified. Designated safety personnel will then forward the Exposure In Utero form to the 
Investigator for completion.  
A subject becoming pregnant while on study drug will immediately be withdrawn from the study 
and EOT study procedures will be performed. 
The subject or partner should be followed by the Investigator until completion of the pregnancy. 
If the pregnancy ends for any reason before the anticipated date, the Investigator should notify 
designated safety personnel. At the completion of the pregnancy, the Investigator will document 
the outcome of the pregnancy. SAE reporting procedures should be followed if the outcome of 
the pregnancy meets the criteria for immediate classification as an SAE (i.e. postpartum 
complication, spontaneous abortion, stillbirth, neonatal death, or congenital anomaly). 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
69 
9 
DATA MANAGEMENT AND RECORD KEEPING 
9.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the clinical research associate (CRA) 
during monitoring visits. The CRA will verify data recorded in the EDC system with source 
documents. All corrections or changes made to any study data must be appropriately tracked in 
an audit trail in the EDC system. An eCRF will be considered complete when all missing, 
incorrect, and/or inconsistent data has been accounted for and electronically signed by the 
Investigator or assignee. 
Data will be processed using a validated computer system conforming to regulatory 
requirements. 
9.2 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure user name and password in order to enter, review, or 
correct study data. These procedures must comply with Title 21 of the Code of Federal 
Regulations (21 CFR Part 11) and other appropriate international regulations. All passwords will 
be strictly confidential. 
9.3 
Medical Information Coding 
For medical information, the following thesauri will be used: 
• Latest version of MedDRA (version 18.1 or higher) for medical history and AEs, and 
• World Health Organization Drug Dictionary Enhanced (Sept. 2015 or later) for prior and 
concomitant medications. 
9.4 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the data, will be applied to the data in order to ensure accurate, 
consistent, and reliable data. Data identified as erroneous, or data that are missing, will be 
referred to the site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator in order to be 
considered complete. 
9.5 
Record Keeping 
Records of subjects, source documents, monitoring visit logs, eCRFs, inventory of study drugs, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data is defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
70 
are contained in source documents (original records or certified copies). These records will be 
retained in a secure file for the period as set forth in the Clinical Study Agreement. Prior to 
transfer or destruction of these records, the Sponsor must be notified in writing and be given the 
opportunity to further store such records.  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
71 
10 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
10.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human subjects. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study 
subjects are protected, consistent with the principles that have their origin in the Declaration of 
Helsinki, and that the clinical study data are credible. 
10.2 
Investigator Requirements 
Each Investigator must provide the Sponsor and/or its designee a completed and signed Form 
FDA 1572 and a Financial Disclosure Form. All sub-Investigators must be listed on Form FDA 
1572 and Financial Disclosure Forms must be completed for all sub-Investigators listed on Form 
FDA 1572. 
A Coordinating Investigator will be identified for multicenter trials conducted in the EU and 
Australia. The Coordinating Investigator will be selected on the basis of active participation in 
the trial, thorough knowledge of the therapeutic area being studied, and the ability to interpret 
data. 
10.2.1 
Disposition and Accountability of Investigational Products 
The Investigator is responsible for the control of investigational products under study. An 
investigational product dispensing log must be kept current and should contain the following 
information: 
• The identification number for each subject who is administered the investigational product 
• The date(s) and quantity of the investigational product administered to the subject 
• Documentation of proper disposal of used investigational product vials or unused vials 
subjected to temperature excursion 
• Documentation of proper disposal (or return, at Sponsor’s request) of unused investigational 
product vials. 
The Investigator is responsible for investigational product accountability during on-site 
monitoring visits. All records and used/unused supplies of the investigational product must be 
available for inspection at every monitoring visit. 
The study sites, per institutional guidelines, will destroy used investigational product vials after 
formulation for administration. The formulation of investigational product for administration and 
the destruction of each used vial will be documented in the investigational product accountability 
log. Unused investigational product will be destroyed at the study site after final investigational 
product accountability and notification by Sponsor, unless otherwise directed by Sponsor. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
72 
10.3 
Institutional Review Board/Ethics Committee 
The IRB/EC will review all appropriate study documentation in order to safeguard the rights, 
safety, and well-being of subjects. The study will only be conducted at sites where IRB/EC 
approval has been obtained. The protocol, IB, ICF, advertisements (if applicable), written 
information given to the subjects, safety updates, annual progress reports, and any revisions to 
these documents will be provided to the IRB/EC by the Investigator. 
Federal regulations and International Council on Harmonisation (ICH) require that approval be 
obtained from an IRB/EC prior to participation of subjects in research studies. Prior to study 
onset, the protocol, any protocol amendments, ICFs, advertisements to be used for subject 
recruitment, and any other written information regarding this study to be provided to a subject or 
subject’s legal guardian must be approved by the IRB/EC. 
No study drug will be released to the site for dosing until written IRB/EC authorization has been 
received by the Sponsor. 
10.4 
Informed Consent 
The ICF and any changes to the ICF made during the course of the study must be agreed to by 
the Sponsor or designee and the IRB/EC prior to its use and must be in compliance with all ICH 
GCP, local regulatory requirements, and legal requirements.  
The Investigator must ensure each study subject is fully informed about the nature and objectives 
of the study and possible risks associated with participation and must ensure the subject has been 
informed of his/her rights to privacy. The Investigator will obtain written informed consent from 
each subject before any study-specific activity is performed and will document consent was 
obtained prior to enrollment in the study in the source documentation. The original signed copy 
of the ICF must be maintained by the Investigator and is subject to inspection by a representative 
of the Sponsor, auditors, the IRB/EC, and/or regulatory agencies. A copy of the signed ICF will 
be given to the subject. 
10.5 
Study Monitoring Requirements 
To ensure the study is conducted in accordance with the protocol and ICH GCP, the study 
monitor will aid the Investigator and, at the same time, the Sponsor in the maintenance of 
complete, legible, well organized and easily retrievable data. Before the enrollment of any 
subject in this study, the Sponsor or their designee will review with the Investigator and site 
personnel the following documents: protocol, IB, eCRFs and procedures for their completion, 
informed consent process, study drug management, and the procedure for reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. 
During monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data are 
entered by the site, the monitor will review the data for safety information, completeness, 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
73 
accuracy, and logical consistency. Computer programs that identify data inconsistencies may be 
used to help monitor the clinical study. If necessary, requests for clarification or correction will 
be sent to Investigators. The Investigator and his/her staff will be expected to cooperate with the 
monitor and provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the site by signature and date on the study-specific monitoring log. 
10.6 
Disclosure of Data 
Data generated by this study must be available for inspection by health and regulatory authorities 
(such as FDA, Health Canada, European Medicines Authority, and others), the Sponsor or 
designee, and the IRB/EC as appropriate. Subjects or their legal representatives may request their 
medical information be given to their personal physician or other appropriate medical personnel 
responsible for their welfare. 
Subject medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 
10.7 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participating subjects (sufficient information to 
link records, e.g. eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE 
forms, source documents, and detailed records of treatment disposition. The records should be 
retained by the Investigator according to specifications in the ICH guidelines, local regulations, 
or as specified in the Clinical Study Agreement, whichever is longer. The Investigator must 
obtain written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor 
should be prospectively notified. The study records must be transferred to an acceptable 
designee, such as another Investigator, another institution, or to the Sponsor.  
10.8 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication 
rights until mutual agreement on the content, format, interpretation of data in the manuscript, and 
journal selected for publication are achieved. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
74 
10.9 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR §54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a 
period of 1 year after the completion of the study. 
10.10 
Insurance and Indemnity 
In accordance with the relevant national regulations, the Sponsor has taken out subject liability 
insurance for all subjects who have given their consent to the clinical study. This cover is 
designed for the event that a fatality, physical injury, or damage to health occurs during the 
clinical study’s execution. 
10.11 
Legal Aspects 
The clinical study is submitted to the relevant national competent authorities in all participating 
countries to achieve a clinical trial authorization (CTA). 
The study will commence (i.e. initiation of study centers) when the CTA and favorable ethics 
opinion have been received.  

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
75 
11 
REFERENCES 
A'Hern RP. Sample size tables for exact single-stage phase II designs, Stat Med 2001; 20: 859-
66. 
Ahmed I, Ahmed Tipu S, Ishtiaq S. Malignant mesothelioma, Pak J Med Sci 2013; 29: 1433-8. 
Alley EW, Molife LR, Santoro A, Beckey K, Yuan S, Cheng JD, Piperdi B, Schellens JHM. 
Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients 
with malignant pleural mesothelioma: Preliminary results from KEYNOTE-028, Cancer 
Res 2015; 75: CT103-CT03. 
American Cancer Society. Malignant Mesothelioma. 2014. American Cancer Society. 
http://www.cancer.org/asc/groups/cid/documents/webcontent/003119-pdf.pdf. 
Anraku M, Cunningham KS, Yun Z, Tsao MS, Zhang L, Keshavjee S, Johnston MR, de Perrot 
M. Impact of tumor-infiltrating T cells on survival in patients with malignant pleural 
mesothelioma, J Thorac Cardiovasc Surg 2008; 135: 823-9. 
Bahjat KS, Liu W, Lemmens EE, Schoenberger SP, Portnoy DA, Dubensky TW, Jr., Brockstedt 
DG. Cytosolic entry controls CD8+-T-cell potency during bacterial infection, Infect 
Immun 2006; 74: 6387-97. 
Basch E, Hesketh PJ, Kris MG, Prestrud AA, Temin S, Lyman GH. Antiemetics: american 
society of clinical oncology clinical practice guideline update, J Oncol Pract 2011; 7: 
395-8. 
Boffetta P. Epidemiology of peritoneal mesothelioma: a review, Ann Oncol 2007; 18: 985-90. 
Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, et al. 
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid 
tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates, J Clin 
Oncol 2010; 28: 3167-75. 
Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a review, MedGenMed 
2007; 9: 32. 
Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W CD, Portnoy 
DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity 
from toxicity, Proc Natl Acad Sci U S A 2004; 101: 6. 
BVL. Opinion of CCBS for classifying Listeria monocytogenes strains with deletions in the 
genes prfA, hly, actA, actA und plcB. 1999. Federal Office of Consumer Protection and 
Food Safety. 
http://www.bvl.bund.de/EN/06_Genetic_Engineering/genetic_engineering_node.html. 
Byrne MJ and Nowak AK. Modified RECIST criteria for assessment of response in malignant 
pleural mesothelioma, Ann Oncol 2004; 15: 257-60. 
Carbone M, Ly BH, Dodson RF, Pagano I, Morris PT, Dogan UA, Gazdar AF, Pass HI, Yang H. 
Malignant mesothelioma: facts, myths, and hypotheses, J Cell Physiol 2012; 227: 44-58. 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
76 
CTFG. Recommendations related to contraception and pregnancy testing in clinical trials. 2014. 
Clinical Trial Facilitation Group, Accessed Jun 16. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. 
Dramsi S, Biswas I, Maguin E, Braun L, Mastroeni P, Cossart P. Entry of Listeria 
monocytogenes into hepatocytes requires expression of inIB, a surface protein of the 
internalin multigene family, Mol Microbiol 1995; 16: 251-61. 
Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the 
general U.S. population, Am J Respir Crit Care Med 1999; 159: 179-87. 
Hassan R, Alley EW, Kindler HL, Antonia SJ, Jahan TM, Honarmand S, McDougall K, et al. 
CRS-207 immunotherapy expressing mesothelin, combined with chemotherapy as 
treatment for malignant pleural mesothelioma (MPM), J Clin Oncol 2016; 34: abstr 8558. 
Hassan R, Bera T, Pastan I. Mesothelin: a new target for immunotherapy, Clin Cancer Res 2004; 
10: 3937-42. 
Hassan RA, S.J; Alley, E.W.; Kindler, H.L.; Jahan, T.; Grous, J.J.; Honarmand, S.; McDougall, 
K.; Whiting, C.C.; Nair, N.; Lemmens, E.; Tsujikawa, T.; Kumar, S.; Coussens, L.; 
Murphy, A. L.; Thomas, A.; Brockstedt, D.G. CRS-207, a mesothelin-targeted 
immunotherapy, in combination with standard of care chemotherapy as treatment for 
malignant pleural mesothelioma (MPM) 2015. 
Hazarika M, White RM, Jr., Booth BP, Wang YC, Ham DY, Liang CY, Rahman A, et al. 
Pemetrexed in malignant pleural mesothelioma, Clin Cancer Res 2005; 11: 982-92. 
Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, Sterman DH, et al. A live-
attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing 
mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune 
induction, Clin Cancer Res 2012; 18: 858-68. 
Le DT, Dubenksy TW, Jr., Brockstedt DG. Clinical development of Listeria monocytogenes-
based immunotherapies, Semin Oncol 2012; 39: 311-22. 
Merck. 2014. "Pembrolizumab (KEYTRUDA) prescribing information." In Whitehouse Station, 
NJ. 
Miettinen M and Sarlomo-Rikala M. Expression of calretinin, thrombomodulin, keratin 5, and 
mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 
596 tumors in comparison with epithelioid mesotheliomas of the pleura, Am J Surg 
Pathol 2003; 27: 150-8. 
Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. General 
considerations for lung function testing, Eur Respir J 2005; 26: 153-61. 
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, et al. 
Standardisation of spirometry, Eur Respir J 2005; 26: 319-38. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group, Am J Clin Oncol 
1982; 5: 649-55. 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
77 
Portnoy DA, Auerbuch V, Glomski IJ. The cell biology of Listeria monocytogenes infection: the 
intersection of bacterial pathogenesis and cell-mediated immunity, J Cell Biol 2002; 158: 
409-14. 
Quispel-Janssen J, Zimmerman M, Buikhuisen W, Burgers S, Zago G, Baas P. 2016. "MS04.07: 
Nivolumab in malignant pleural mesothelioma (Nivomes): An interim analysis." In 13th 
International Conference of the International Mesothelioma Interest Group. 
Birmingham, UK. 
Rice D, Rusch V, Pass H, Asamura H, Nakano T, Edwards J, Giroux DJ, et al. 
Recommendations for uniform definitions of surgical techniques for malignant pleural 
mesothelioma: a consensus report of the international association for the study of lung 
cancer international staging committee and the international mesothelioma interest group, 
J Thorac Oncol 2011; 6: 1304-12. 
Robinson BW and Lake RA. Advances in malignant mesothelioma, N Engl J Med 2005; 353: 
1591-603. 
Shen H, Slifka MK, Matloubian M, Jensen ER, Ahmed R, Miller JF. Recombinant Listeria 
monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell-
mediated immunity, Proc Natl Acad Sci U S A 1995; 92: 3987-91. 
Slifka MK, Shen H, Matloubian M, Jensen ER, Miller JF, Ahmed R. Antiviral cytotoxic T-cell 
memory by vaccination with recombinant Listeria monocytogenes, J Virol 1996; 70: 
2902-10. 
Spirtas R, Beebe GW, Connelly RR, Wright WE, Peters JM, Sherwin RP, Henderson BE, et al. 
Recent trends in mesothelioma incidence in the United States, Am J Ind Med 1986; 9: 
397-407. 
Sugarbaker DJ, Mentzer SJ, DeCamp M, Lynch TJ, Jr., Strauss GM. Extrapleural 
pneumonectomy in the setting of a multimodality approach to malignant mesothelioma, 
Chest 1993; 103: 377S-81S. 
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, et 
al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer, N Engl J Med 
2012; 366: 2443-54. 
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, et 
al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in 
patients with malignant pleural mesothelioma, J Clin Oncol 2003; 21: 2636-44. 
Zalcman G, Mazieres J, Margery J, Greillier L, Audigier-Valette C, Moro-Sibilot D, Molinier O, 
et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma 
Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, 
phase 3 trial, Lancet 2015. 
 

Aduro Biotech, Inc. 
Clinical Study Protocol ADU-CL-13 
 
Confidential & Proprietary 
Version 2.0, 14 June 2017 
79 
INVESTIGATOR AGREEMENT 
STUDY TITLE: A Phase 2 Single-arm Study to Evaluate Safety and Efficacy of CRS-207 
with Pembrolizumab in Adults with Previously-Treated Malignant Pleural Mesothelioma 
By signing below I agree that: 
I have read the protocol and agree it contains all necessary details for carrying out the study as 
described. I will conduct this study in accordance with the design and specific provisions of this 
protocol and will make a reasonable effort to complete the study within the time designated. I 
will provide copies of this protocol and access to all information furnished by Aduro Biotech to 
study personnel under my supervision. I will discuss this material with them to ensure they are 
fully informed about the study product and study procedures. I will let them know this 
information is confidential and proprietary to Aduro Biotech and may not be further disclosed to 
third parties. I understand that the study may be terminated or enrollment suspended at any time 
by Aduro Biotech, with or without cause. I have the right to suspend enrollment of subjects at 
my study site if necessary to protect the best interests of the study subjects. 
I agree to conduct this study in full accordance with United States Food and Drug Administration 
Regulations, Institutional Review Board/Ethics Committee Regulations, and International 
Conference on Harmonisation (ICH) Guidelines for Good Clinical Practices. 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name