A Phase 1 Study Evaluating High Dose ADXS11-001 Treatment in Women With Carcinoma of the Cervix (ADXS001-07)
Phase: PHASE1
Conditions: Effects of Immunotherapy, Metastatic/Recurrent Cervical Cancer, Cervical Adenocarcinoma, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma, Cervical Small Cell Carcinoma, Stage III Cervical Cancer, Stage IVA Cervical Cancer, Stage IVB Cervical Cancer
Sponsor: Advaxis, Inc.

 
 
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PROTOCOL ADXS001-07 
A PHASE 1 STUDY EVALUATING HIGH DOSE ADXS11-001 
TREATMENT IN WOMEN WITH CARCINOMA OF THE CERVIX 
 
 
SPONSOR: 
ADVAXIS, INC. 
305 COLLEGE ROAD EAST 
PRINCETON, NJ 08540 
609-452-9813 (OFFICE) 
609-452-9818 (FAX) 
 
 
Original Version 1.0: 
 
March 26, 2014 
Amendment 1.0/Version 2.0:   
December 19, 2014 
Amendment 2.0/Version 3.0:   
March 13, 2015 
Amendment 3.0/Version 4.0:   
June 12, 2015 
Amendment 4.0/Version 5.0: 
August 10, 2015 
Amendment 5.0/Version 6.0: 
December 1, 2015 
Amendment 6.0/Version 7.0: 
January 4, 2016 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained herein is confidential and proprietary and may not be 
disclosed, reproduced, or circulated without the prior written consent of Advaxis 
Incorporated 
 

 
 
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PROTOCOL APPROVAL 
Protocol Number: 
 
ADXS001-07 
Title of Protocol: 
A Phase 1 Study Evaluating High Dose ADXS11-001 
Treatment in Women with Carcinoma of the Cervix 
 
Original Version 1.0: 
 
 
March 26, 2014 
Amendment 1.0/Version 2.0: 
 
December 19, 2014 
Amendment 2.0/Version 3.0: 
 
March 13, 2015 
Amendment 3.0/Version 4.0: 
 
June 12, 2015 
Amendment 4.0/Version 5.0: 
 
August 10, 2015 
Amendment 5.0/Version 6.0: 
 
December 1, 2015 
Amendment 6.0/Version 7.0: 
 
January 4, 2016 
 
 
Prepared by:  
                        
 
____________________________________ 
_____________________ 
Date 
Advaxis Inc. 
    
Approved by: 
 _____________________________________  
_____________________ 
Date 
Advaxis Inc. 
 
 
 
PI
PI

 
 
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SUMMARY OF CHANGES 
FOR PROTOCOL AMENDMENT 6.0 
# 
Section 
Page 
Revision 
Rationale 
1 
Synopsis 
11-13 
Updated length of subject trial 
duration from 2 to 5 years, included 
the 6 month oral antibiotic course 
and Lm Surveillance Monitoring 
requirements, updated the Main 
Criteria for Eligibility and updated 
language for ADXS11-001 
 
 
 
Updated adverse event tracking to 
extend until completion of the Lm 
Surveillance Monitoring phase. 
Administrative update in 
support of the FDA 
recommendations. 
2 
List of 
Abbreviations  
14-15 
Updated to include CMP, CRP, ESR, 
TNFα and PI3K.  
Administrative update. 
3 
3.2 ADXS11-001 
Immunotherapy 
18 
Section header and content were 
revised with AXDS11-001 
information. 
Administrative update  
4 
3.3 ADXS11-001 
Mechanism Action 
18-19 
Section header and content were 
revised with AXDS11-001 
mechanism of action. 
Administrative update 
5 
3.4.1 Summary of 
Safety of ADXS11-
001 
19-21 
Section was updated with safety data 
information. 
Safety administrative 
update  
6 
3.4.1.1  
Delayed/Late 
Listeria Infection 
21-22 
Safety Section revised to include 
clinical experience to-date with Lm 
clearance and the description of the 
index case of delayed/late listeria 
infection.  
Per FDA Safety Section, 
revised to inform 
investigators/patients on 
the recent delayed/late 
listeria event.  
7 
5.2 Exclusion 
Criteria (#14) 
28 
New exclusion criterion was added 
to exclude subjects with implanted 
devices that pose high risks for 
colonization or inability of removal. 
Exclusion criteria added 
to mitigate risk of 
colonization of foreign 
bodies and medical 
devices   
8 
5.2 Exclusion 
Criteria(#15) 
28 
New exclusion criterion was added 
to exclude subjects who are receiving 
or are expected to receive treatment 
with  PI3K or TNFα inhibitors 
during study participation or in 
future. 
Exclusion criteria added 
to mitigate risk of listeria 
infection.  
PI

 
 
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# 
Section 
Page 
Revision 
Rationale 
9 
5.2 Exclusion 
Criteria #16 
28 
New exclusion criterion was added 
to exclude subjects with a known 
contraindication (e.g. 
allergies/sensitivities) to the 
administration of trimethoprim 
sulfamethoxazole and/or ampicillin. 
Exclusion criterion 
added based on FDA 
recommendation of 
prophylaxis and 6-month 
antibiotic treatment. 
10 
5.2 Exclusion 
Criteria (#21) 
29 
New exclusion criterion added to 
exclude subjects who have 
undergone a major surgery or had a 
newly implanted artificial 
(prosthetic) joint(s), implants and/or 
devices where a minimum of 6 
weeks has not elapsed from the time 
of surgery.  Additional requirements 
for the resolution of all toxicities 
and/or complications was included.  
Exclusion criteria added 
as a required safety 
update to mitigate 
potential listeria events. 
11 
6 Study Design and 
Treatment Plan  
29 
Updated antibiotic regimen added. 
Inclusion added based on 
FDA recommendation of 
antibiotic regimen for 
prophylaxis during study 
treatment and 6 month 
course post-treatment.   
12 
7.3 Patient Study 
Participation 
33 
New section added to detail patient 
study participation duration. 
Updated to include the 3 
year Lm Surveillance 
Monitoring Phase 
13 
Table 5:  Schedule 
of Events  
34-35 
Added Lm Surveillance Monitoring 
schedule which includes a 6 month 
post ADXS11-001 antibiotic 
(Trimethoprim/Sulfamethoxazole) 
treatment to mitigate the risk of 
delayed listeria infection. 
Text clarified in the table footnotes 
for consistency with the revised 
corresponding study procedure. 
Safety updates and 
administrative 
clarifications per FDA 
recommendation. 
14 
8.1 Study 
Procedures 
36-38 
Prior/Concomitant Therapies and 
Procedures and Adverse Events     
updated to require 6 month post-
study treatment antibiotics as well as 
recording of adverse/serious events 
from the time informed consent is 
signed through the completion of Lm 
Surveillance period. Updated to 
require antibiotic usage to be 
documented on the respective 
eCRFs.    
Safety updates and 
administrative 
clarifications per FDA 
recommendation. 

 
 
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# 
Section 
Page 
Revision 
Rationale 
Surgical History – surgical history 
will be obtained for all subjects. 
Surgical procedures that occur after 
study enrollment will be documented 
separately. 
Prophylactic Medications – NSAIDS 
doses and antiemetic administration 
will be done per label or package 
insert. 
Coagulation Profile – will be 
assessed at Screening only. 
Dispense/Prescribe Oral Prophylactic 
Antibiotics section updated with 
details for on study and post study 
antibiotic regimen. 
15 
8.5 Safety Follow-
Up/Post-Treatment 
Visit 
39-40 
New paragraphs added regarding the 
updated Lm Surveillance Monitoring.   
Safety update based on 
FDA recommendation. 
16 
9.1.1 Baseline 
Tumor 
Assessments 
40 
Section was updated by providing 
imaging areas to be included. 
Safety administrative 
change  
17 
10.2.1 Safety 
Precautions 
49 
Section was updated to provide 
further clarification 
Safety administrative 
change  
18 
11.1 ADXS11-001 
Pretreatment 
Prophylaxis 
Regimen  
51 
Section was updated for revisions to 
the IV fluids volume and 
premedication regimen clarification 
Safety administrative 
change  
19 
11.3 Administration 
of ADXS11-001  
52 
New paragraph added to note that 
 
 
 
 
 
 
 
 
Safety update to mitigate 
potential listeria events. 
20 
11.5.1 and 11.5.2 
Listeria Infection 
Identification and 
Management   
57-59 
New sections provide information on 
the identification process and 
management of potential/confirmed 
listeria infection. 
Safety administrative 
change added to provide 
information on the 
identification and 
management of listeria. 
21 
11.7 Major and 
Minor Surgery and 
ADXS11-001 
Treatment  
61 
New section added to describe the 
minimum time period required 
between major surgery and treatment 
administration for patients prior to 
and during study treatment. 
Safety update to mitigate 
potential listeria events. 
PI

 
 
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# 
Section 
Page 
Revision 
Rationale 
22 
12 Concurrent 
Therapies and 
Procedures 
62-63 
Added PI3K and TNFα to the list of 
prohibited therapies. 
Safety update to include 
FDA recommendations.  
23 
13.2 Collection of 
Safety Information 
64 
Updated to include tracking of 
adverse events and serious adverse 
events during the 3 year Lm 
Surveillance Monitoring period. 
Safety update to align 
with FDA 
recommendations. 
24 
13.8 Laboratory 
Test Abnormalities,  
Table 13, 
Laboratory Tests 
71-72 
Additional lab tests including Lm 
Blood cultures, ESR and CRP was 
added to the table.   
Table footnotes updated to detail Lm 
Surveillance Monitoring 
requirements. 
Safety update to include 
FDA recommendations 
for the identification of 
listeria infection. 
25 
Throughout 
protocol 
 
 
  
Safety administrative 
change 
26 
Throughout 
protocol 
 
ADXS11-001 250 mL will be 
infused intravenously over 
 
 
Safety administrative 
change 
 
PI

 
 
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INVESTIGATOR SIGNATURE PAGE 
Protocol No.:  
 
 
 
ADXS001-07 
Title: 
 
 
A Phase 1 Study Evaluating High Dose  
 
 
ADXS11-001 Treatment in Women with  
 
 
Carcinoma of the Cervix 
Original Version 1.0: 
 
 
March 26, 2014 
Amendment 1.0/Version 2.0: 
 
December 19, 2014 
Amendment 2.0/Version 3.0: 
 
March 13, 2015 
Amendment 3.0/Version 4.0: 
 
June 12, 2015 
Amendment 4.0/Version 5.0: 
 
August 10, 2015 
Amendment 5.0/Version 6.0: 
 
December 1, 2015 
Amendment 6.0/Version 7.0  
 
January 4, 2016 
 
By signing below, the Investigator agrees to adhere to the protocol as outlined and agrees 
that any changes to the protocol must be approved by Advaxis, Inc. prior to seeking 
approval from the approving Institutional Review Board (IRB)/Ethical Review 
Committee (ERC). 
This study will be conducted in accordance with Good Clinical Practices (GCPs), 
International Conference on Harmonisation (ICH) Guidelines, the Declaration of 
Helsinki, and local ethical and legal requirements. 
 
Investigator Name:  
 
 _____________________________________  
______________________ 
Signature 
Date 
 
 _____________________________________  
______________________ 
PI Name (Printed) 
Site # 
 
 

 
 
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TABLE OF CONTENTS 
 
List of Tables ....................................................................................................................10 
List of Figures ...................................................................................................................10 
1 
Synopsis .....................................................................................................................11 
2 
List of Abbreviations ................................................................................................14 
3 
Background and Rationale ......................................................................................16 
3.1 
Cervical Cancer and Its Relationship to the Human Papillomavirus .............16 
3.2 
ADXS11-001 Immunotherapy ............................................................................18 
3.3 
ADXS11-001 Mechanism of Action ....................................................................18 
3.4 
Previous Clinical Experience with ADXS11-001 ..............................................19 
3.4.1 
Summary of Safety of ADXS11-001 .............................................................19 
3.4.2 
Summary of Efficacy for ADXS11-001 Studies in Cervical Cancer .........22 
3.5 
Study Rationale ....................................................................................................24 
4 
Objectives ..................................................................................................................25 
4.1 
Primary Objectives ..............................................................................................25 
4.2 
Secondary Objectives...........................................................................................25 
5 
Subject Selection .......................................................................................................25 
5.1 
Inclusion Criteria .................................................................................................25 
5.2 
Exclusion Criteria ................................................................................................27 
6 
Study Design and Treatment Plan ..........................................................................29 
6.1 
Dose Limiting Toxicity Criteria ..........................................................................32 
7 
Investigational Centers .............................................................................................33 
7.1 
Subject Accrual ....................................................................................................33 
7.2 
Subject Enrollment ..............................................................................................33 
7.3 
Subject Study Participation ................................................................................33 
8 
Study Evaluation .......................................................................................................33 
8.1 
Study Procedures .................................................................................................36 
8.2 
Screening Evaluations .........................................................................................38 
8.3 
Study Cycle Evaluation .......................................................................................39 
8.4 
End of Therapy Evaluations ...............................................................................39 
8.5 
Safety Follow-Up/Post-Treatment Visits ...........................................................39 
9 
Evaluation Criteria ...................................................................................................40 
9.1 
Safety .....................................................................................................................40 
9.1.1 
Baseline Tumor Assessments ........................................................................40 
9.1.2 
Tumor Imaging and Assessment of Disease ................................................40 
9.1.3 
Measurable and Non-Measurable Lesions and Disease .............................41 
9.1.4 
Target/Non-Target Lesions ...........................................................................41 
9.1.5 
Response in Measurable Lesions (RECIST 1.1) .........................................41 
9.1.6 
Immune-Related Response in Measurable Lesions (irRECIST) ...............42 
9.1.7 
Response in Non-Measurable Lesions (RECIST 1.1) .................................43 
9.1.8 
Immune-Related Response in Non-Measurable Lesions ............................44 
9.1.9 
Overall Response ............................................................................................44 
9.1.10 
Best Overall Response (RECIST 1.1) ...........................................................45 

 
 
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9.1.11 
Immune-Related Best Overall Response (irRECIST) ................................46 
9.1.12 
Treatment after Initial Evidence of Radiologic Disease Progression ........47 
10 Investigational Drug Product ..................................................................................47 
10.1 
Packaging and Labeling ......................................................................................47 
10.1.1 
Storage and Handling Requirements ...........................................................48 
10.1.2 
Returns and Reconciliation ...........................................................................48 
10.1.3 
Destruction of ADXS11-001 ..........................................................................48 
10.2 
ADXS11-001 Records at Investigational Site ....................................................49 
10.2.1 
Safety Precautions ..........................................................................................49 
11 Clinical Safety management ....................................................................................51 
11.1 
ADXS11-001 Pretreatment Prophylaxis Regimen ............................................51 
11.2 
Step-Up Regimen for ADXS11-001 Pre-Dose Treatment Prophylaxis ...........52 
11.3 
Administration of ADXS11-001 ..........................................................................52 
11.4 
Supportive Care Guidelines ................................................................................52 
11.4.1 
Cytokine Release Symptoms .........................................................................52 
11.4.2 
Nausea/vomiting .............................................................................................56 
11.5 
Management of Infusion Reactions ....................................................................56 
11.5.1 
Listeriosis and Listeria Infection - Identification and Management.........57 
11.5.2 
Management and Surveillance of Listeria during Study 
Participation ...................................................................................................58 
11.6 
ADXS11-001 Toxicities and Treatment .............................................................59 
11.6.1 
Treatment Modification Guidelines .............................................................60 
11.6.2 
ADXS11-001 Treatment Alterations ............................................................60 
11.7 
Major and Minor Surgeries and ADXS11-001 Treatment ..............................61 
11.8 
Discontinuation of Study Subjects ......................................................................61 
11.8.1 
Subject Study Discontinuation Criteria .......................................................61 
11.8.2 
Suspension or Discontinuation of the Study ................................................62 
12 Concurrent Therapies and Procedures ..................................................................62 
13 Adverse Event Reporting in Clinical Trials ...........................................................63 
13.1 
Importance of Adverse Event Reporting ...........................................................63 
13.2 
Collection of Safety Information ........................................................................64 
13.3 
Adverse Event Follow-Up....................................................................................65 
13.4 
Adverse Events Related to Study Conditions ....................................................65 
13.5 
Overdose ...............................................................................................................65 
13.6 
Evaluating Adverse Events .................................................................................66 
13.7 
Handling and Reporting of Adverse Events to the Sponsor ............................70 
13.7.1 
Serious Adverse Events .................................................................................70 
13.8 
Laboratory Test Abnormalities ..........................................................................71 
13.9 
Other Safety Considerations ...............................................................................73 
13.10 Pregnancy .............................................................................................................73 
14 Data Analysis and Statistical Considerations.........................................................74 
14.1 
Introduction ..........................................................................................................74 
14.2 
Statistical Analysis Plan ......................................................................................74 
14.3 
Sample Size ...........................................................................................................74 
14.4 
Treatment Randomization and Blinding ...........................................................75 
14.5 
Study Populations ................................................................................................75 

 
 
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14.5.1 
Subject Disposition.........................................................................................75 
14.5.2 
Demographic Information and Baseline Characteristics ...........................75 
14.5.3 
Protocol Deviation ..........................................................................................75 
14.5.4 
Analysis of Safety ...........................................................................................75 
14.5.5 
Analysis of Efficacy ........................................................................................76 
14.6 
Interim Analysis ...................................................................................................76 
15 Investigator Obligations ...........................................................................................77 
15.1 
Compliance with the Protocol and Protocol Revision ......................................77 
15.2 
Informed Consent ................................................................................................77 
15.2.1 
Informed Consent Procedures ......................................................................77 
15.2.2 
Update of Informed Consent.........................................................................78 
15.3 
Monitoring for Protocol Compliance .................................................................78 
15.4 
Records and Reports............................................................................................78 
15.5 
Institutional Review Board/Independent Ethics Committee ...........................79 
15.6 
Records Retention ................................................................................................80 
16 References ..................................................................................................................81 
 
 
LIST OF TABLES 
Table 1  Number (%) of Subjects with Adverse Events >5% Incidence (Safety 
Population, N=230) ..................................................................................19 
Table 2  Number (%) of Subjects with Adverse Events >5% with Respect to 
Relationship (Possibly Related, Probably Related and Related) (Safety 
Population, N=230) ..................................................................................21 
Table 3  Adequate Organ Function Laboratory Values...............................................26 
Table 4  Trial Treatment .................................................................................................29 
Table 5  Schedule of Events.............................................................................................34 
Table 6  Tumor Response Evaluation:  Comparison of RECIST 1.1 and 
irRECIST ..................................................................................................44 
Table 7  Best Overall Response (RECIST 1.1) ..............................................................45 
Table 8  Immune-Related Best Overall Response (irBOR) .........................................46 
Table 9  Recommended Management Guidelines for Adverse Events Associated 
with Cytokine Release..............................................................................54 
Table 10  Recommended Management Guidelines for Infusion Reactions ................57 
Table 11  Treatment Delay/Discontinuation Guidelines for Drug-Related Adverse 
Events ........................................................................................................60 
Table 12  Evaluating Adverse Events ............................................................................67 
Table 13  Laboratory Tests .............................................................................................72 
 
LIST OF FIGURES 
Figure 1  3+3 Design Schematic ......................................................................................30 

 
 
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1 SYNOPSIS 
Sponsor: 
Advaxis, Inc. 
Name of Finished Product: 
ADXS11-001 
Type of Treatment: 
Lm-LLO Immunotherapy 
Study Title: 
Phase 1 Study Evaluating High Dose ADXS11-001 Treatment In Women With Carcinoma of the 
Cervix 
Type of Study: 
Open-label, Phase 1 
Study Centers: Multi-center 
Objectives: 
The primary objective of the study is: 
a)  To evaluate the tolerability and safety of ADXS11-001 in subjects with persistent, metastatic, or 
recurrent squamous and non-squamous carcinoma, adenosquamous, or adenocarcinoma of the cervix 
Secondary objectives: 
a)  To evaluate tumor response and progression-free survival (PFS) by Response Evaluation Criteria in 
Solid Tumors (RECIST) 1.1 and immune-related RECIST (irRECIST) criteria 
b)  To evaluate and describe the data from correlative immunologic studies of ADXS11-001 treatment 
Methodology: 
In this Phase 1, dose-escalation, open-label, multi-center study, subjects with persistent, metastatic, or 
recurrent carcinoma of the cervix who have failed conventional therapy will receive ADXS11-001 
every 3 weeks during a 12- week treatment cycle.  Subjects will receive a prophylactic regimen to be 
completed at least 
prior to each ADXS11-001 infusion to mitigate and manage potential 
immune response seen with immunotherapy administration.  In addition, all subjects will participate in 
a 3-year Lm surveillance period.  The surveillance period will begin following the last dose of study 
treatment or at the time of study discontinuation.  This period is intended to help ensure the eradication 
of Lm bacteria.  This period will also include a 6-month course of trimethoprim/ sulfamethoxazole 
which will be initiated 72 hours at the completion of the last dose of ADXS11-001 or immediately 
following study discontinuation. 
Doses will be escalated in the standard 3 + 3 fashion, starting with 5 x 109 colony forming units (CFU) 
to a maximum dose level of 1 x 1010 CFU.  Dose cohorts of 3 subjects each will be treated.  In the 
absence of dose-limiting toxicity (DLT) as defined in Section 6.1 Dose Limiting Toxicity assessed 
during the first treatment cycle, the dose will be escalated to the next dose level for the next 3 subjects.  
If DLT is seen in 1 of 3 subjects, another 3 subjects will be treated at that same dose.  If DLT is seen in 
2 of 6 subjects, then that dose level will be considered maximum tolerated dose (MTD) and the 
previous dose level will be selected as the recommended Phase 2 dose (RP2D).  The RP2D will be 
selected based on an observed DLT rate of < 33%. 
Treatment cycles can be repeated at the RP2D (or less) for an individual subject until a discontinuation 
criterion is met.  Discontinuation criteria include documented disease progression, intolerable side 
effects not resolved with dose reduction or change in premedications or the subject completes 1 cycle 
of treatment post observation of complete response (CR) per RECIST 1.1 and immune-related RECIST 
criteria (irCR). 
PI

 
 
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Sponsor: 
Advaxis, Inc. 
Name of Finished Product: 
ADXS11-001 
Type of Treatment: 
Lm-LLO Immunotherapy 
Further assessment of the RP2D level may be explored in an expansion cohort in subjects with 
persistent, metastatic, or recurrent carcinoma of the cervix who have failed conventional therapy to 
evaluate the safety and clinical activity of ADXS11-001.  Treatment will continue for each subject until 
a discontinuation criterion is met.  The end of treatment will be defined as 1 year after the last subject’s 
first treatment or until that subject has met a discontinuation criterion. All subjects will be followed for 
adverse events (AEs) and serious adverse events (SAEs) from the time written informed consent is 
signed through the completion of the Lm surveillance period. 
Safety will be assessed by comparing treatment-related AEs, changes in physical examinations, vital 
sign measurements, laboratory abnormalities and Lm surveillance monitoring. 
Immunologic effects will be measured and evaluated by collection of peripheral blood for preparation 
of peripheral blood mononuclear cells (PBMCs) and serum in cycle 1 only.  PBMCs will be analyzed 
for the presence and quantitation of HPV-E7 and HPV–E6 specific CD8+ T-cells through ELISpot and 
other assays as well as T regulatory cells and myeloid-derived suppressor cells.  PBMC immunologic 
gene expression analysis may also be conducted.  Serum will be evaluated for serum cytokines, 
chemokines, and other potential markers.   
Number of Subjects Planned: 
The dose escalation portion of the study will enroll between 6-12 subjects based on observed AEs 
and/or DLTs within the dose cohorts.  Additional subjects may be enrolled in an expansion cohort at 
the RP2D level to allow approximately 15 subjects to be treated at that dose level. 
Diagnosis and Main Criteria for Eligibility: 
 
Women at least 18 years of age with histologically-confirmed, measurable and/or evaluable 
disease as defined by RECIST 1.1 
 
Subject has persistent, metastatic, or recurrent squamous and non-squamous carcinoma, 
adenosquamous, or adenocarcinoma of the cervix with documented disease progression that is 
not amenable to surgery or standard radiotherapy 
 
Subject may have received ≤2 prior regimens for disease in the metastatic setting.  Subjects 
who have had >2 prior therapies in the metastatic setting MAY be eligible only after 
consultation with the Investigator and the Sponsor.  
 
Subjects should have no major existing co-morbidities or medical conditions that will preclude 
therapy in the view of the principal investigator 
 
Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 
or 1, and a life expectancy of at least 6 months (to be able to complete 1 study cycle) 
 
Subjects should not have rapidly progressing disease 
 
Subjects must be able to tolerate trimethoprim/sulfamethoxazole and ampicillin. 
 
Subjects must not have implanted medical device(s) that pose a high risk for colonization 
and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, 
orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)).  More 
common devices and prosthetics such as:  arterial and venous stents, dental and breast implants 
and venous access devices such as Mediports are permitted.  Subjects with any other devices or 
implants must be approved by Sponsor prior to participation.  

 
 
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Sponsor: 
Advaxis, Inc. 
Name of Finished Product: 
ADXS11-001 
Type of Treatment: 
Lm-LLO Immunotherapy 
 
Subjects who have undergone a major surgery or who have a new artificial implant and/or 
medical device which meets eligibility criteria must have a minimum 6-week time period 
elapsed from the time of surgery to the initiation of study treatment.  
 
Subjects who are receiving or are expected to receive future treatment with PI3K or TNF 
inhibitors. 
Test Product, Dose, Mode of Administration: 
ADXS11-001 is a live attenuated bioengineered strain of Listeria monocytogenes (Lm)-LLO.  
 
 
  
 
 
 
Reference Therapy: 
None 
Study Duration: 
Each subject will participate in the trial for up to 5 years from the time the subject signs informed 
consent through the final study contact.  The study duration includes an active study treatment phase 
(~24 months) and a 3-year Lm surveillance monitoring period, which includes 6 months of oral 
antibiotic administration to commence upon completion of the active study treatment phase or upon 
study discontinuation. 
Criteria for Evaluation: 
Safety:  Recorded AEs; physical examinations, including vital sign measurements; clinical laboratory 
evaluations; Lm surveillance blood cultures 
Efficacy:  Tumor response and progression free survival (PFS) 
Immunologic effects:  Collection and analysis of peripheral blood  
Statistical Methods: 
Descriptive statistics will be used to summarize and evaluate the outcomes. 
Demographic and baseline subject characteristics will be summarized.  AEs will be classified and 
summarized by type, incidence, severity, and causality.  All AEs will be summarized by subject, dose 
level, and prior recurrence history (aggressive/non-aggressive).  All subjects who received at least 1 
dose of ADXS11-001 will be included in the safety analyses.   
Disease response will be tabulated for all subjects who receive ADXS11-001.  PFS is defined as the 
time from first dose of study treatment until objective tumor progression or death.  Subjects who have 
not progressed or who are still alive at the time of evaluation will be censored for the analysis.  Kaplan-
Meier curves and descriptive statistics will be used to summarize PFS. 
 
PI

 
 
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2 LIST OF ABBREVIATIONS 
ALT 
alanine transaminase 
APC 
anaphase-promoting complex  
AST 
aspartate transaminase 
BMBL 
Biosafety in Microbiological and Biomedical Laboratories 
BOR 
best overall response 
 
 
BUN 
blood urea nitrogen 
CBC 
Complete blood count 
CFU 
colony forming unit(s) 
CIN 
cervical intraepithelial neoplasia 
CMP 
Comprehensive metabolic panel  
CR 
complete response 
CRF 
case report form 
CRP 
C-reactive Protein 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose limiting toxicity 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ELISA 
enzyme-linked immunosorbent assay 
ESR 
Erythrocyte sedimentation rate 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl-transferase 
GMP 
Good Manufacturing Practice  
GOG 
Gynecologic Oncology Group 
HPV 
human papillomavirus  
ICC 
invasive cervical cancer 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board  
irBOR 
immune-related best overall response 
irCR 
immune-related complete response 
irPD 
immune-related progressive disease 
irPR 
immune-related partial response 
irRC 
immune-related response criteria 
irRECIST 
immune-related Response Evaluation Criteria in Solid Tumors 
irSD 
immune-related stable disease 
IV 
intravenous 
LDH 
lactic dehydrogenase 
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LLO 
listeriolysin O 
Lm 
Listeria monocytogenes 
MDSCs 
myeloid-derived suppressor cells 
MHC 
major histocompatibility complex 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NSAID 
nonsteroidal anti-inflammatory drug(s) 
PBMCs 
peripheral blood mononuclear cells 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival  
PI3K 
Phosphoinositide 3-kinase  
PR 
partial response 
pRB 
retinoblastoma protein 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QID 
four times a day 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAER 
Serious Adverse Event Report 
SCID 
severe combined immunodeficiency 
SD 
stable disease 
SOP 
Standard Operating Procedure 
SumD 
sum of the longest diameters  
TAAs 
tumor associated antigens 
tLLO 
truncated listeriolysin O 
TMTB 
total measurable tumor burden 
TNF 
Tumor necrosis factor alpha 
Treg 
T regulatory cells 
ULN 
upper limit of normal 
US, USA 
United Stated of America 
WBC 
white blood cell 
 

 
 
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3 BACKGROUND AND RATIONALE 
3.1 
Cervical Cancer and Its Relationship to the Human Papillomavirus 
Cervical cancer is the second most common cancer in women worldwide and the most 
common cancer in developing countries.[1]  .  Worldwide, over half a million women are 
diagnosed with cervical cancer each year, predominantly in under-developed countries, 
where most cases present at an advanced stage due to lack of effective cervical cancer 
screening systems.[1]  In the United States (US), it is estimated that 12,340 women were 
diagnosed with cancer of the cervix, and 4,030 women died of the disease in 2013.[2] 
The human papilloma virus (HPV) is now recognized to be the primary etiologic agent 
for cervical carcinogenesis, and cervical cancer is the first cancer recognized by the 
World Health Organization to be 100% attributable to an infection with high-risk HPV 
genotypes.[1]  However, the majority of HPV-infected individuals have an asymptomatic 
course, with clearance of the virus occurring within 1 or 2 years in 90% of cases.  Ten 
percent of individuals experience persistent HPV infection, which increases their risk of 
developing invasive cancers.  Ultimately, approximately one-half of the 10% of 
individuals with persistent HPV infection will develop malignant disease, a process that 
may take up to 30 years.[3] 
Although many HPV types have been associated with cervical neoplasia, types 16, 18, 
31, 35, 39, 45, 51, 52, 56, and 58 cause most invasive cancers and are considered “high-
risk” HPV-genotypes.  HPV-16 accounts for approximately 53% of invasive cervical 
cancer (ICC) cases in most countries, followed by HPV-18, which accounts for 
approximately 13%.[4]  The high-risk HPV genotypes produce 2 oncoproteins, 
designated E6 and E7, which bind and inactivate the tumor suppressor’s p53 and 
retinoblastoma protein (pRB), respectively.  The E6 mediated inhibition of p53 blocks 
apoptosis, whereas E7 inhibition of pRB abrogates cell cycle arrest leading to deregulated 
cellular proliferation and ultimately malignancy.[5] 
Persistent HPV infection may lead initially to abnormal changes in cervical cells, termed 
cervical dysplasia or cervical intraepithelial neoplasia (CIN).  However, CIN is a distinct 
clinic pathological entity from ICC and defines premalignant lesions (namely CIN 2/3) 
that, if left untreated, may eventually progress to ICC.  However, these lesions have a 
high rate of spontaneous remission and can be curatively treated with a minor 
gynecologic surgical procedure such as loop electrical electrosurgical procedure or a cone 
biopsy. 
In the US, most cases of ICC are detected at early stages because of the implementation 
of cervical cancer screening programs.  Staging of ICC is usually based on the American 
Joint Committee on Cancer or the International Federation of Gynecology and Obstetrics 
system, which are similar.  Approximately 60% of ICC cases are diagnosed at stage I, 
25% at stage II, 10% at stage III, and 5% at stage IV.[6]  Standard treatments for ICC 
include surgery, radiation alone, chemotherapy alone, or combination 
radiation/chemotherapy.  Surgery and radiation therapy are considered to be equally 

 
 
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effective for early-stage, small-volume disease.  For more advanced disease, that is not 
reliably curable by surgery, additional treatments including radiation and potentially 
systemic chemotherapy are required.  Several clinical trials have shown an overall 
survival advantage with cisplatin concurrent with radiation therapy (chemoradiation), and 
chemoradiation with cisplatin is the currently recommended treatment for locally 
advanced cervical cancer.[7]  Platinum doublet chemotherapy is currently recommended 
as standard of care for patients with recurrent cervical cancer that is not amenable to 
surgery or radiation.[7]  In general, survival correlates with stage, with a 5-year survival 
for stage IA of almost 100%, stage IB2 and IIB 50%–75%, stage III 30%-50%, and stage 
IV 15%.  For locally recurrent disease, pelvic exenteration can lead to a 5-year survival 
rate of 32%-62% in selected patients.[7] 
Although most cases of early-stage cervical cancer can be cured, treatments are 
associated with significant long-term morbidity [7] and most have an impact on fertility.  
Cisplatin, the most commonly used and most active therapy, has produced response rates 
ranging from 20%-30% and overall survival of less than 10 months.[8]  In addition, 
patients with recurrent disease will typically have already received cisplatin concurrent 
with radiotherapy as a first-line therapy, and may no longer be sensitive to cisplatin.[9]  
In view of the low level of success with cytotoxic therapies, and the poor prognosis of 
patients with advanced cervical cancer, there is certainly an unmet medical need for 
novel, more efficacious, less toxic therapeutic approaches for ICC. 
For over 3 decades, the Gynecologic Oncology Group (GOG) has studied a number of 
cytotoxic agents and combinations for the treatment of women with recurrent/metastatic 
cervical cancer.  After the identification of cisplatin as a drug with significant activity, 
GOG Phase 3 trials focused on the development of cisplatin-containing regimens that 
might yield superior results compared to single-agent therapy.  Unfortunately, the higher 
response rates associated with combination therapy often did not result in improved 
survival.  Median survival in this patient population remains less than 1 year and 
combination therapy leads to more adverse effects, particularly myelosuppression.  Most 
patients with recurrent and/or metastatic cervical cancer may no longer be sensitive to 
cisplatin-based chemotherapy as they most likely have already received cisplatin 
concurrent with radiotherapy as a first line therapy and, thus, experience treatment-
related toxicity with no derived benefit from further cisplatin treatment.[9]  When tumor 
responses do occur, they typically are of short duration.  Furthermore, the widespread 
acceptance of adding cisplatin to radiation treatment as a radiation sensitizer in first-line 
chemoradiation treatment of ICC means that most patients with recurrent cervical cancer 
have already been treated with cisplatin.  This prior exposure significantly reduces the 
effectiveness of cisplatin or carboplatin for recurrent cervical cancer.  Recently, the 
results of the GOG 240 Phase 3 study were published where the addition of bevacizumab 
to combination chemotherapy was associated with a 3.7 month improvement in median 
overall survival in patients with advanced cervical cancer.[9, 10]  However, cisplatin 
containing chemotherapy regimens continue to be the standard of care in this patient 
population worldwide.[8]  Despite this, there continues to be a large unmet medical need 
for agents with different mechanisms of action (such as antiangiogenics, checkpoint 

 
 
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inhibitors, or therapeutic HPV immunotherapies) that when used alone or in combination 
can improve the survival of patients with recurrent cervical cancer. 
3.2 
ADXS11-001 Immunotherapy 
ADXS11-001 is a live attenuated Listeria monocytogenes (Lm) immunotherapy, 
developed for the treatment of HPV-associated cancers.  ADXS11-001 is bioengineered 
to secrete an antigen-adjuvant fusion protein (tLLO-HPV-E7) consisting of a truncated 
fragment of the listeriolysin O (truncated LLO, tLLO) fused to the full length E7 peptide 
of HPV-16. 
3.3 
ADXS11-001 Mechanism of Action 
ADXS11-001 is rapidly taken up by antigen presenting cells (APC) within the subject.  
This causes activation of the APC and results in a multi-factorial stimulation of innate 
immunity.  To the subject, this activation can manifest as flu-like symptoms or symptoms 
associated with cytokine release that occur during or in the hours immediately following 
administration.  Once inside the APC, ADXS11-001 can escape the phagolysosome into 
the cytoplasm where it secretes the HPV-E7-tLLO fusion protein.  This peptide, along 
with other Lm peptides, is very rapidly ubiquitinated and transported to the proteasome 
where the peptides are broken down and cross-presented through major 
histocompatibility complex (MHC) Class 1 and Class 2 pathways.  This cross-
presentation, in immunologic context of responding to a “perceived” acute infection, 
stimulates the development of adaptive immunity culminating in HPV-specific effector 
T-cells that can infiltrate into the tumor microenvironment (TME) and destroy tumor 
cells immunologically. 
Advaxis Lm-LLO immunotherapies have broad effects on the immune system and the 
ability to neutralize mechanisms of immune tolerance.  These Lm-LLO immunotherapies 
take advantage of the ability of Lm to present target antigens in the cytoplasm of APCs 
that generate a target-specific T-cell immunity.  High avidity T-cells are generated where 
possible, but when they are not, Lm stimulates an up-regulation of T-cell responses to 
sub-dominant epitopes.  Advaxis Lm-LLO immunotherapies secrete tumor peptides fused 
to LLO from multiple copies of plasmids.  This increased LLO secretion triggers 
endocrine and exocrine signaling of the immune system that results in a relative reduction 
in the number and function of regulatory T-cells and myeloid-derived suppressor cells 
(MDSC) in the TME, which enables tumor cell killing, even when the T-cells are lower 
avidity.  Tumor antigen specific T-cell immunity generated in the context of Lm-LLO 
immunotherapies can be effective even when targeting self-antigens or viral targets that 
are partially cross-reactive.   
Studies have shown that ADXS11-001 has anti-tumor activity against multiple types of 
high-risk HPV, including cross-reactive activity where there are minor differences in 
HPV E7 T-cell epitopes.  As an investigational drug product, ADXS11-001 has no direct 
effect on the tumor tissue, but is designed to stimulate the subject’s own immune system 

 
 
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to generate an effective immune response targeting the tumor-associated antigen like 
HPV-E7. 
3.4 
Previous Clinical Experience with ADXS11-001 
Refer to the Investigator’s Brochure (IB) for detailed preclinical and clinical data. 
3.4.1 
Summary of Safety of ADXS11-001 
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3.4.1.1 
Delayed/Late Listeria Infection 
ADXS11-001 has been attenuated over
 more in comparison to wild-type (wt)-Lm.  
 
 
 
In a Phase 1 clinical study, in the absence of antibiotics, Lm was rapidly cleared from the 
blood.  No Lm was detected in the blood of any subject beyond 48 hours post-dosing and 
no Lm was detected in the urine and feces in any subject at the highest dose of ADXS11-
001 tested (1 x 1010 CFU) [11]. 
wt-Lm is known to form and persist within biofilms, especially on medical devices 
despite antibiotic treatment [12]. Although rare, medical device–related infections such as 
ventriculo-peritoneal shunt infection, peritoneovenous shunt infection, and prosthetic 
joint infection have been reported [13-16]. ADXS11-001is highly sensitive to antibiotics 
such as ampicillin and sulfamethoxazole/trimethoprim, which can be an effective 
treatment regimen for listeria infection.  Therefore, subjects with implanted medical 
device(s) that pose a high risk for colonization and/or cannot be easily removed are 
excluded from this study.  In addition, all subjects will receive a course of oral antibiotics 
PI
PI
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beginning on Day 4 (approximately 72 hours) after each dose of ADXS11-001 and for 
6 months following the last dose of ADXS11-001 to aid in the eradication of the bacteria. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
3.4.2 
Summary of Efficacy for ADXS11-001 Studies in Cervical Cancer 
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3.5 
Study Rationale 
Since treatment with ADXS11-001 immunotherapy has shown prolonged survival, stable 
disease and objective tumor responses including CRs, and PRs, it may be able to improve 
survival in second-line treatment of recurrent cervical cancer in a clinically meaningful 
way.  This trial proposes to evaluate a high dose of ADXS11-001 (1 x 1010 CFU).  
Depending on the level of toxicity seen in the study, 2 dose levels are possible:  
1 x 1010 CFU and 5 x 109 CFU.  A standard 3 + 3 design will be used to evaluate and 
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determine the maximum tolerated dose (MTD) and subsequent recommended Phase 2 
dose (RP2D).  The standard dose of 1 x 109 CFU is not included as a dose level in this 
study 
 
 
 
 
 
 
 
4 OBJECTIVES 
4.1 
Primary Objectives 
The primary objectives of the study are: 
a) To evaluate the tolerability and safety of ADXS11-001 in subjects with persistent, 
metastatic or recurrent squamous and non-squamous cell carcinoma, 
adenosquamous, or adenocarcinoma of the cervix 
4.2 
Secondary Objectives 
a) To evaluate tumor response and progression-free survival (PFS) by RECIST 1.1 
and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 
b) To evaluate and describe the data from correlative immunologic studies of 
ADXS11-001 treatment 
5 SUBJECT SELECTION 
5.1 
Inclusion Criteria 
1. Subject is at least 18 years of age or older on day of signing informed consent 
2. Subject has histologically-confirmed, persistent, metastatic or recurrent squamous or 
non-squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the 
cervix with documented disease progression (disease not amenable to surgery or 
standard radiotherapy). 
3. Subject may have received ≤2 regimens for disease in the metastatic setting.  Subjects 
who have had >2 prior treatment regimens in the metastatic setting MAY be eligible 
only after consultation with the investigator and the sponsor, and providing all other 
inclusion/exclusion criteria have been met.  Subjects must have either documented 
disease progression OR become intolerant to prior therapy, in the metastatic setting. 
4. Subject has measurable and/or evaluable disease for response assessment per 
RECIST 1.1.  Tumors within a previously irradiated field will be designated as “non-
target” lesions unless progression is documented or a biopsy is obtained to confirm 
persistence at least 90 days following completion of radiation therapy. 
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5. Subject is able to provide written informed consent. 
6. Subject demonstrates adequate organ function as defined in Table 3. All screening 
laboratory testing should be performed within 3 days of treatment initiation. 
Table 3  Adequate Organ Function Laboratory Values 
System 
Laboratory Value 
Hematologic 
Absolute neutrophil count (ANC)a 
≥1,000 /mcL 
Platelets 
≥75,000 / mcL 
Hemoglobin 
≥9 g/dL or ≥5.6 mmol/L  
Renal 
Serum creatinine OR 
Measured or calculatedb creatinine clearance 
(GFR can also be used in place of creatinine or 
CrCl) 
≤1.5 X upper limit of normal (ULN) OR 
 
≥50 mL/min for subject with creatinine levels >1.5 X 
institutional ULN 
Hepatic 
Serum total bilirubin 
≤1.5 X ULN OR  
Direct bilirubin ≤ULN for subjects with total bilirubin 
levels >1.5 ULN 
AST (SGOT) and ALT (SGPT) 
≤2.5 X ULN OR 
≤5 X ULN for subjects with liver metastases 
Coagulation 
International Normalized Ratio (INR) or 
Prothrombin Time (PT) 
≤1.5 X ULN unless subject is receiving anticoagulant 
therapy 
as long as PT or INR is within therapeutic range of 
intended use of anticoagulants 
Activated Partial Thromboplastin Time (aPTT) 
≤1.5 X ULN unless subject is receiving anticoagulant 
therapy 
as long as aPTT is within therapeutic range of intended 
use of anticoagulants 
a ANC, Platelets, Hemoglobin requirement cannot be met by the use of recent transfusions, or growth factor support 
(G-CSF, erythropoietin, etc.) within 2 weeks prior to treatment initiation. 
b Creatinine clearance should be calculated per institutional standard. 
7. Subject has resolved acute effects of any prior therapy to baseline severity of 
Grade <2 per CTCAE except for AEs not constituting a safety risk by investigator 
judgment. 
8. Subject must have an ECOG performance status of 0 or 1. 
9. Women of childbearing potential with a negative urine pregnancy test at Screening. 

 
 
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10. Female subjects of childbearing potential must agree to ongoing use 2 methods of 
study doctor approved birth control or be surgically sterile, or abstain from 
heterosexual activity for the course of the study from Screening through 120 days 
after the last dose of study medication (see Section 13.10).  Subjects of childbearing 
potential are those who have not been surgically sterilized or have not been free from 
menses for >1 year. 
5.2 
Exclusion Criteria 
1. In the opinion of the investigator, subject has rapidly progressing disease, OR has life 
expectancy of less than 6 months, OR would be unable to receive at least 1 cycle of 
therapy. 
2. Subject has received chemotherapy and/or radiation therapy (except palliative 
radiation therapy for disease-related pain) within ≤2 weeks of first ADXS11-001 
infusion. 
3. Subject has not recovered (i.e., Grade ≤1 at baseline) from AEs, with the exception of 
alopecia due to previously administered agent(s). 
4. Subject has a known additional malignancy that is progressing or requires active 
treatment.  Exceptions include basal cell carcinoma of the skin, squamous cell 
carcinoma of the skin, or in situ cervical cancer that has undergone potentially 
curative therapy. 
5. Has an active autoimmune disease requiring systemic treatment within the past 
3 months or a documented history of clinically severe autoimmune disease, or a 
syndrome that requires systemic steroids or immunosuppressive agents.  Subjects 
with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.  
Subjects that require intermittent use of bronchodilators or local steroid injections 
would not be excluded from the study.  Subjects with hypothyroidism stable on 
hormone replacement or Sjorgen’s syndrome will not be excluded from the study. 
6. Has neuropathy (sensory and motor) ≥Grade 3 per CTCAE v 4.03. 
7. Subject has diagnosis of immunodeficiency, is dependent on or has received systemic 
steroid therapy or any other form of immunosuppressive therapy within 7 days prior 
to the first dose of trial treatment with the exception of topical corticosteroids and 
occasional inhaled corticosteroids, as indicated.  
8. Subject has known active central nervous system (CNS) metastases and/or 
carcinomatous meningitis.  Subjects with previously treated brain metastases may 
participate provided they are stable (without evidence of progression by imaging for 
at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms 
have returned to baseline), have no evidence of new or enlarging brain metastases, 
and are not using steroids for at least 7 days prior to trial treatment. 

 
 
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9. Subject has concurrent unstable or uncontrolled medical condition (e.g., active 
uncontrolled systemic infection, poorly controlled hypertension or history of poor 
compliance with an anti-hypertensive regimen, unstable angina, congestive heart 
failure, uncontrolled diabetes) or other chronic disease, which in the opinion of the 
Investigator, could compromise the subject or the study. 
10. Subject is pregnant or breastfeeding, or expecting to conceive a child/children within 
the projected duration of the trial, starting with the pre-screening or screening visit 
through 120 days after the last dose of trial treatment. 
11. Subject is currently participating in or has participated in a study of an investigational 
agent(s) or using an investigational device within 4 weeks of the first dose of trial 
treatment. 
12. Subject has active infection requiring systemic therapy or is dependent on or currently 
receiving antibiotics that cannot be discontinued before dosing.  (Note:  Subjects who 
discontinue an antibiotic prior to dosing must wait at least 5 half-lives after the last 
dose of antibiotic before receiving any ADXS11-001 infusion). 
13. Subject has a known psychiatric or substance abuse disorder(s) that would interfere 
with cooperation with the requirements of the trial. 
14. Subject has implanted medical device(s) that pose a high risk for colonization and/or 
cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, 
orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)).  
NOTE:  More common devices and prosthetics which include arterial and venous 
stents, dental and breast implants and venous access devices (e.g., Port-a-Cath or 
Mediport) are permitted.  Sponsor must be contacted prior to consenting any subject 
who has any other device and/or implant.  
15. Subjects who are receiving or may receive future treatment with PI3K or TNFα 
inhibitors. 
16. Subject with a contraindication (e.g., sensitivity/allergy) to trimethoprim/ 
sulfamethoxazole and ampicillin. 
17. Subject with any other serious or uncontrolled physical or mental condition/disease 
that, as judged by the Investigator, could place the subject at higher risk derived from 
his/her participation in the study, could confound results of the study, or would be 
likely to prevent the subject from complying with the requirements of the study or 
completing the study. 
18. Subject has a known history of human immunodeficiency virus (HIV) (HIV 1/2 
antibodies). 
19. Subject has a known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., 
HCV RNA [qualitative] is detected). 

 
 
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20. Subject has received a live vaccine within 30 days prior to the first dose of trial 
treatment. 
21. Has undergone a major surgery, including surgery for a new artificial implant and/or 
device, within 6 weeks prior to the initiation of ADXS11-001 treatment.  NOTE: All 
toxicities and/or complications must have recovered to baseline or Grade 1 prior to 
the initiation of ADXS11-001 study therapy.  Sponsor must be consulted prior to 
enrolling subjects on the study who recently had a major surgery or have new 
artificial implant, and/or devices. 
22. Subject has a known allergy to any component of the study treatment formulations. 
23. Subject has a history of listeriosis or prior ADXS11-001 therapy. 
6 STUDY DESIGN AND TREATMENT PLAN 
In this Phase 1, open-label, multi-center study, subjects with persistent, metastatic or 
recurrent squamous cell or non-squamous cell carcinoma, adenosquamous carcinoma, or 
adenocarcinoma of the cervix who have failed conventional therapy will receive the 
highest dose tolerated of ADXS11-001 infused intravenously (IV) 
 
(± 10 minutes) with overall infusion volume of 250 mL on Day 1 of Weeks 1, 4, 7, and 
10 of each 12-week cycle.  Subjects must complete the prophylactic regimen at least 
prior to each ADXS11-001 infusion (as noted in Section 11.1) to mitigate and 
manage the potential immune response seen with immunotherapy administration. 
Subjects who experience a DLT during the dose escalation portion of the study or 
experience events described as a DLT in any subsequent treatment cycle will be 
discontinued from study treatment.  However, if the subject who experienced a DLT 
shows significant response to ADXS11-001, they may be eligible to receive ADXS11-
001 at a lower dose level for subsequent doses and cycles following discussion and 
agreement between the Investigator and Sponsor.  See Section 6.1 Dose Limiting 
Toxicity Criteria for definition of DLT. 
The treatment to be used in this trial is outlined below in Table 4.  Trial treatment should 
begin on the day of randomization or as close as possible to the date on which the 
treatment level is allocated/assigned. 
Details on the dose calculation, preparation and administration are provided in the 
Pharmacy Manual. 
Table 4  Trial Treatment 
Dose Level 
ADX11-001 
Schedule 
1 
5 x 109 CFU 
Q3wks 
2 
1 x 1010 CFU 
Q3wks 
-1 
1 x 109 CFU 
Q3wks 
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ADXS11-001 will be given as a 
 250 mL IV infusion every 
3 weeks in repeating 12-week cycles 
A standard 3 + 3 design will be used in the dose escalation portion of the study.  
ADXS11-001 will be administered in sequential cohorts of 3-6 subjects, with a minimum 
of 48 hours between initial dosing for each of the first 3 subjects treated at each dose 
level.  The first cohort will enroll a minimum of 3 subjects, according to a standard 3 + 3 
design shown schematically in Figure 1. 
Figure 1  3+3 Design Schematic 
 
 
Subjects in the first cohort will receive a dose of ADXS11-001 5 x 109 CFU 
(Dose Level 1). 
 
If no DLTs are experienced in the 28 day DLT observation period at Dose 
Level 1, the next dose level of ADXS11-001 1 x 1010 CFU (Dose Level 2) 
will be explored. 
 
If 1 DLT is experienced at Dose Level 2 (ADXS1-001 1 x 1010 CFU), then 3 
additional subjects will be enrolled at that same dose level.  If there is 1 DLT 
among the 6 subjects, then the Dose Level 2 may be identified as the RP2D 
and will be expanded to further define safety and efficacy. 
 
If ≥2 DLTs are observed within 28 days of dosing for subjects in the first dose 
cohort, the starting dose of ADXS11-001 will be de-escalated to 1 x 109 CFU 
and a dose de-escalation cohort may be enrolled (Dose Level -1). 
All decisions regarding dose level escalation or de-escalation will be guided by the 3 + 3 
study design and will be made by the Sponsor in consultation with the Investigator(s).  

 
 
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The RP2D will be selected based on an observed DLT rate of <33%.  The Sponsor 
reserves the right to expand the number of subjects in each of the cohorts to better 
evaluate safety and tolerability.  Cohorts will be expanded in groups of 3 subjects. 
Following identification of the RP2D, additional subjects may be enrolled into the 
expansion cohort to allow approximately 15 subjects to be treated at that dose level.  All 
subjects in the Dose Expansion Cohort may be enrolled simultaneously. 
DLTs will only be assessed during the first 28 days in cycle 1 (See Section 6.1, Dose 
Limiting Toxicity Criteria, for DLT definition).  Transient hypotension which may 
require IV fluids for management is an expected event that subjects may experience with 
ADXS11-001 infusions.  Subjects with signs of cytokine release symptoms ≥Grade 3 (per 
CTCAE v 4.03) that persist for more than 24 hours despite symptomatic treatment, will 
be judged to have a DLT.  Blood cultures will not be obtained on a routine basis but will 
be collected in subjects who have persistent fever 24 hours after the end of ADXS11-001 
infusion.  Subjects will receive a 7-day course of either oral 80 mg trimethoprim / 400 mg 
sulfamethoxazole once daily or 160 mg trimethoprim / 800 mg sulfamethoxazole (DS) 3 
times over the course of the 7 days.  Subjects with known allergy to sulfa drugs may 
receive ampicillin 500 mg 4 times daily for 7 days beginning on Day 4 (approximately 72 
hours) after each study treatment infusion.  A subject who experiences a fever (CTCAE 
Grade 1 or greater) 24 hours following the completion of ADXS11-001 infusion should 
be started on NSAIDS, hydration and other appropriate measures to treat the fever. In the 
event that the fever persists or worsens 48 hours following the completion of ADXS11-
001 infusion then oral or broad spectrum IV antibiotics should be considered based on the 
subject’s medical condition. If the fever remains unresponsive to oral/IV antibiotics 72 
hours following the completion of the infusion then a blood culture should be obtained to 
evaluate for listeremia and determine the appropriate treatment course for the subject. 
Study cycles can be repeated at the RP2D (or less) for each subject until a discontinuation 
criterion is met.  Criteria include documented disease progression, intolerable side effects 
not resolved with dose reduction or change in pre-medications, or the completion of 1 
cycle of treatment post observation of complete response per RECIST 1.1 and immune-
related RECIST criteria (irCR). 
Safety will be assessed by comparing treatment-related AEs, changes in physical 
examinations, vital sign measurements, and laboratory abnormalities. 
Immunologic effects will be measured and evaluated by collection of peripheral blood for 
preparation of peripheral blood mononuclear cells (PBMCs) and serum immediately prior 
to each ADXS11-001 infusion and 2 weeks after every ADXS11-001 infusion in Cycle 1 
only (Day 1 of Weeks 3, 6, 9, and 12).  PBMCs will be analyzed for the presence and 
quantitation of HPV-E7 and HPV–E6 specific CD8+ T-cells through ELISpot and other 
assays as well as Treg cells and MDSCs.  PBMC immunologic gene expression analysis 
may also be conducted.  Serum will be evaluated for serum cytokines, chemokines, and 
other potential markers.  Blood will be collected in Cycle 1 only at 3 time points 
immediately prior to each ADXS11-001 infusion and 2 hours and 4 hours post infusion 
(±15 minutes- Day 1 of Weeks 1, 4, 7, and 10). 

 
 
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Subjects should arrive at the study center on the days of their scheduled ADXS11-001 
administration in order to be evaluated, have laboratory specimens collected before 
treatment commences, and complete the study prophylactic regimen at least
pre-infusion before receiving the ADXS11-001 infusion. 
Subjects will remain at the study site for a minimum of 4 hours after the infusion for 
safety observations, and if necessary treatment of side effects resulting from the study 
treatment administration.  Treatment and observation of side effects may take up to an 
additional 4 hours, so subject arrival at the study center should be early enough to 
accommodate a possible 9-hour visit day.  Vital signs will be taken pre-dose then every 
 after the infusion as a safety measure. 
After the initial study cycle, subjects who respond or have immune-related SD at or after 
tumor assessments may receive additional treatment at the same dose and schedule, until 
either evidence of disease progression, intolerable side effects not resolved with dose 
reduction or change in premedications, or for 1 completed study cycle post achievement 
of CR per RECIST 1.1 and immune-related RECIST criteria (irCR).  These subjects may 
continue to be evaluated for response every 12 weeks. 
Study treatment will be modified as per Table 11 in Section 11.6.1 Treatment 
Modification Guidelines. 
6.1 
Dose Limiting Toxicity Criteria 
DLT will be evaluated during the first 28 days of the first cycle during the dose escalation 
portion of the trial.  All toxicities will be graded using CTCAE v 4.03.  The occurrence of 
any of the following toxicities will be considered a DLT, if judged by the Investigator to 
be possibly, probably or definitely related to therapy.  Treatment modifications for DLT 
are shown in Table 11. 
Hematologic: 
1. Grade 4 hematologic toxicity. 
2. Febrile Neutropenia, defined as absolute neutrophil count (ANC) < 1000/mm3 with a 
single temperature of >38.3° C (101° F) or a sustained temperature of >38° C (100.4° 
F) for more than 1 hour. 
3. Grade 3 thrombocytopenia lasting >72 hours.  
4. Grade 4 thrombocytopenia. 
Non-Hematologic: 
1. ≥Grade 3 non-hematologic toxicity, (excluding nausea, vomiting and/or diarrhea 
lasting <3 days and reversible with medical intervention). 
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2. Grade 3 non hematologic laboratory values, (excluding transient Grade 3 laboratory 
value abnormalities, hematologic and non-hematologic, reversible within 5 days and 
without necessity for medical intervention).    
3. Listeremia: positive blood cultures(s) along with persistent (for 72 hours post dose) 
symptoms consistent with listeremia (e.g., fever and muscle aches, often preceded by 
diarrhea or other gastrointestinal symptoms). 
4. ≥Grade 3 flu-like symptoms or cytokine release symptoms that persist for >24 hours 
after study treatment administration despite symptomatic treatment. 
7 INVESTIGATIONAL CENTERS 
This is a multi-center study.  
7.1 
Subject Accrual 
Subjects will be recruited from a population of patients with recurrent, metastatic, or 
persistent squamous and non-squamous cell carcinoma, adenosquamous or 
adenocarcinoma of the cervix.  The subject’s medical record, including the most recent 
treatment, will be reviewed by the Investigator to determine the suitability of the subject 
for the study. 
7.2 
Subject Enrollment 
Each subject who gave signed informed consent and was screened for admission into the 
study will be assigned a unique sequential number that also includes their study site.  The 
identification number and the subject’s initials should be recorded on all case report 
forms (CRFs) and correspondence regarding the subject following study registration. 
7.3 
Subject Study Participation 
Each subject may participate in the study for up to 5 years from the time informed 
consent is signed through the final study contact.  This includes a study treatment phase 
(~24 months), a 3-year post-ADXS11-001 treatment Lm surveillance period which 
includes a prophylactic oral antibiotic administration period (6 months) and Lm 
surveillance monitoring approximately every 3 months for 3 years.  It is expected that a 
subject will participate in the study until the completion of the full 3-year Lm surveillance 
period.  However, following the completion of the 6 month oral antibiotic treatment, a 
subject will be eligible to participate in other investigational clinical studies.  
8 STUDY EVALUATION 
The key study procedures and the frequency of their occurrences are outlined in Table 5. 

 
 
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Table 5  Schedule of Events 
 
Screening1 
12 Week Treatment Cycle2 
End of 
Follow-Up 
Study Procedure 
Days  
-28 to 0 
Wk 14 
Pre   I  Post 
Wk 
2 
Wk 
35 
Wk 
4 
Wk 
5 
Wk 
65 
Wk 
7 
Wk 
8 
Wk 
95 
Wk 
10 
Wk 
11 
Wk 
12 
Therapy6 
Administrative Procedures 
 
Informed consent7 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics/Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical History8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior Cancer History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/Concomitant Medications 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Non Drug Treatment/Procedures9 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Prophylactic Medication10 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
ADXS11-001 Administration11 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
Dispense/Prescribe Oral 
Prophylactic Antibiotics12 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
Phone Call3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Procedures/Assessments 
 
Review Adverse Events (AE)13 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
Physical exam14 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Vital Signs15 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
ECOG Performance Status 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Laboratory Procedures/Assessments16 
 
CBC with Differential 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Serum Chemistry Panel 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Coagulation Profile17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Dipstick 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Pregnancy Test18 
X 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Lm Surveillance Monitoring19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Efficacy Measurements/Correlative Studies 
 
Tumor Imaging20 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Immune monitoring/T Cell21  
 
X 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
 
 
Cytokines22  
 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
1 
Screening procedures, including tumor evaluations will be performed within 28 days prior to first dose of study treatment to determine study eligibility.   
2 
Repeating 12-week treatment cycles.   

 
 
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3 
Safety Follow-Up will be conducted via a telephone call 30 days (± 5 days) after the last ADXS11-001 infusion to confirm the resolution of any new or ongoing AEs 
or SAEs. 
4 
At every ADXS11-001 infusion, the indicated pre and post procedures will be performed. 
5 
Week 3, Week 6 and Week 9 visits will be performed during Cycle 1 only.  After cycle 1, these visits are not required. 
6 
End of Therapy is not a visit.  Assessments noted here must be completed upon the decision to discontinue a subject from study treatment. 
7 
Informed Consent must be obtained prior to conducting screening evaluations. 
8 
Documentation of non-cancer surgeries, including, but not limited to artificial (prosthetic) joints, implants and/or devices, such as port/stent implant placed prior to 
study enrollment. 
9 
Documentation of any on-study non-drug treatment and surgical procedures, including but not limited to artificial (prosthetic) joints, implants and/or devices. 
10 
The pretreatment prophylactic regimen will be administered prior to and completed at least 
 before each ADXS11-001 infusion. 
11 
ADXS11-001 may be administered ± 7 days within Day 1 of each scheduled infusion. ADXS11-001 should not be administered less than 2 weeks apart without 
Sponsor approval.  
12 
All subjects will receive a 7-day course of oral antibiotic therapy starting 72 hours after administration of ADXS11-001.  All subjects will also receive an additional 6-
month oral antibiotic course to be initiated 72 hours following the last dose of study treatment or  upon discontinuation of study treatment.   
13 
AEs and SAEs will be assessed from the time Informed Consent is obtained through the completion of the Lm surveillance period. .  All AE/SAEs will be followed 
through resolution.  All AEs/SAEs experienced during this period must be recorded on the eCRF. 
14 
Physical Examinations are to be completed prior to the ADXS11-001 administration to confirm safety criteria for study drug administration are met.  PEs may be 
performed more frequently, as clinically indicated. Height will be measured at screening only.  Weight will be collected prior to each ADXS11-001 infusion. 
15 
Monitor vital signs every 
 following the completion of every ADXS11-001 infusion. 
16 
All laboratory procedures are to be completed and assessed by the investigator within 3 days prior to the administration of study treatment to confirm safety criteria for 
study treatment administration are met. 
17 
Coagulation profile will be assessed at screening only. 
18 
A pregnancy tests must be performed within 72 hours prior to each ADXS11-001 infusion for female subjects of childbearing potential or less than 1 year 
postmenopausal.  If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 
19 
Lm surveillance will include routine monitoring of CBC, CMP (including CRP, ESR) and blood cultures.  Following completion of study treatment all assessments will be 
performed every 3 months (±2 weeks) for 3 years beginning 3 months after the subject’s last dose of study treatment. 
20 
Baseline tumor imaging and assessments must be performed within 28 days prior to the first ADXS11-001 infusion in the first study cycle.  Subsequent tumor imaging 
and assessments will be conducted at Week 12 (±1 week) for the duration of study participation.  Apparent progression within the first 12 weeks, not accompanied by 
clinical deterioration, should be confirmed ≥4 weeks later. 
21 
Immune monitoring/T-cell samples will be collected immediately prior to each ADXS11-001 infusion (Day 1 of Weeks 1, 4, 7, and 10) and between 11-14 days after 
every ADXS11-001 infusion in Cycle 1 only. 
22 
Cytokine samples will be collected in Cycle 1 only at 3 time points immediately prior to each ADXS11-001 infusion and 2 hours and 4 hours post infusion (±15 
minutes- Day 1 of Weeks 1, 4, 7, and 10). 
 
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8.1 
Study Procedures 
A series of clinical tests and procedures will be performed to assess toxicity and response 
throughout the study.  The evaluations for this study will include: 
1. Informed Consent - each subject must sign a copy of the most current Institutional 
Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent 
document.  A copy of the signed document will be maintained with the subject’s 
records. 
2. Medical History - past or current medical conditions, current medications, and 
medications taken within 30 days of study entry. 
3. Surgical History - A surgical history will be obtained by the Investigator or qualified 
designee.  Surgical history will include all clinically relevant surgeries including, but 
not limited to artificial (prosthetic) joints, implants and/or devices, such as ports or 
stents.  Surgical procedures that occur after study enrollment will be documented 
separately. 
4. Prior Cancer History - A prior cancer history will be obtained by the Investigator or 
qualified designee.  The prior cancer history will include histological confirmation of 
cancer, tumor staging (refer to the most current American Joint Committee on Cancer 
Staging Manual, the fifth edition or higher), and prior cancer therapies and best 
response(s), if applicable. 
5. Prior/Concomitant Therapies and Procedures- All prescription and nonprescription 
medication (excluding vitamins and nutritional supplements) taken by the subject 
from 28 days prior to signing informed consent and up to and including the 
completion of the 3-year Lm surveillance period will be recorded in the medical 
record and on the eCRF.   
6. AEs/SAEs- The Investigator or qualified designee will assess each subject to evaluate 
for potential new or worsening AEs/SAEs from the time written informed consent is 
obtained through the completion of the 3-year Lm surveillance period of the study.  
AEs/SAEs experienced during this period will be reported and recorded in the eCRF.  
AEs will be graded and recorded throughout the study according to CTCAE v 4.03 
(see Section 13.6).  Toxicities will be characterized in terms regarding seriousness, 
causality, toxicity grading, and action taken with regard to study treatment.   
7. Physical Examination - evaluation by body system. 
8. Vital Sign Measurements - temperature, pulse, respiration rate, and blood pressure 
and weight will be taken pre-dose then every
 
 after 
each infusion of ADXS11-001.  Weight will be taken pre-dose only.  Height will be 
measured at screening only. 
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9. Prophylactic Medications - The pretreatment prophylactic regimen will be 
administered prior to and be completed at least
before each ADXS11-001 
infusion as outlined in Section 11.1.  Subjects may continue to receive NSAIDs doses  
and antiemetic administration per label or package insert, as needed following 
ADXS11-001 infusions 
10. ECOG Performance Status Score - according to the ECOG performance status 
criteria. 
11. Hematology Profile - a complete blood count (CBC) with differential, and platelet 
count. 
12. Chemistry Profile - glucose, total protein, albumin, uric acid, blood urea nitrogen 
(BUN), creatinine, lactic dehydrogenase (LDH), AST, ALT, alkaline phosphatase, 
total bilirubin, sodium, potassium, bicarbonate, chloride, and calcium. 
13. Coagulation Profile – international normalized ratio (INR) or prothrombin time (PT) 
and activated partial thromboplastin time (aPTT) will be assessed at screening only. 
14. Urinalysis – routine dipstick measurements and, if clinically indicated, microscopic 
analysis. 
15. Urine Pregnancy Test – A urine pregnancy test will be performed for all women of 
child bearing potential.  A positive urine pregnancy test must be confirmed by a 
serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of βHCG). 
16. Dispense/Prescribe Oral Prophylactic Antibiotics – (1) During Study Treatment 
Phase - All subjects will receive a 7-day course of oral antibiotic therapy starting 
approximately 72 hours (Day 4) after administration of ADXS11-001.  Antibiotic 
therapy should consist of either 160 mg trimethoprim/800 mg sulfamethoxazole (DS) 
tablet administered 3 times during the 7 consecutive days or 80 mg trimethoprim/400 
mg sulfamethoxazole administered daily for 7 consecutive days or for subjects with 
sulfa allergy ampicillin 500 mg 4 times daily for 7 consecutive days may be 
administered. (2) Post Study Treatment - All subjects will receive a 6-month course 
of oral trimethoprim/sulfamethoxazole or ampicillin for subjects with sulfa allergy to 
be initiated approximately 72 hours following the last dose of study treatment or at 
the time of study discontinuation.  The dose of trimethoprim/sulfamethoxazole 
consists of either 160 mg trimethoprim/800 mg sulfamethoxazole (DS) tablet 
administered 3 times a week or 80 mg trimethoprim/400 mg sulfamethoxazole 
administered daily.  The dose of ampicillin consists of 500 mg 4 times daily for 6 
months.  Review the approved product labeling for Bactrim and ampicillin, and 
monitor antibiotic tolerance as dosing adjustments may be necessary. 
17. Tumor Imaging– Computed tomography (CT) and magnetic resonance imaging 
(MRI) will be considered the best currently available and reproducible methods to 
measure target lesions (as defined in Section 9.1.4, Definition of Target/Non-target 
Lesions) selected for response assessment.  Baseline tumor imaging/disease 
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assessment must be performed within 28 days prior to the first dose of study drug.  
Then imaging studies and tumor assessments will be performed every 12 weeks 
(± 1 week) after the initial ADXS11-001 infusion.  Apparent progression within the 
first 12 weeks, not accompanied by clinical deterioration, should be confirmed ≥4 
weeks later.  (See Section 9.1.12, Tumor Response). 
18. Immune Monitoring - The generation of E6 and E7 specific immune responses in the 
peripheral blood will be assessed by ELISpot or enzyme-linked immunosorbent assay 
(ELISA) based assays.  Blood for immune monitoring will be collected immediately 
prior to every ADXS11-001 infusion and 2 weeks after each ADXS11-001 infusion in 
cycle 1 only (Day 1 of Weeks 1, 3, 4, 6, 7, 9, 10, and 12). 
o T cell ELISpot - For blood collection, peripheral blood samples 
(around 50 mL total) will be withdrawn at the time points specified 
above.  Whole blood will be processed over a Ficoll gradient to 
obtain PBMC, and PBMC will be washed, counted, aliquotted and 
frozen in dimethyl sulfoxide-containing freezing medium prior to 
long-term storage in liquid nitrogen.  Sterile technique will be 
maintained throughout so that viable cells may be cultured and 
assayed after thawing.  The peptide pools of E6 and E7 antigens 
for determination of immune responses will be provided by 
Advaxis. 
19. Cytokines/Chemokines – Blood for cytokine and chemokine analysis will be 
collected in Cycle 1 only at 3 time points immediately prior to each ADXS11-001 
infusion and 2 hours and 4 hours post infusion (± 15 minutes) Day 1 of Weeks 1, 4, 7, 
and 10. 
8.2 
Screening Evaluations 
All subjects must undergo Screening evaluations prior to the first ADXS11-001 infusion.  
Screening evaluations used to determine the subject’s study eligibility must be completed 
within 28 days prior to the first ADXS11-001 infusion and include the following:  
histological confirmation of persistent, metastatic or recurrent squamous or non-
squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix, 
tumor evaluations, medical history, prior and concomitant therapies; physical 
examination; vital sign measurements including weight, height (at Screening only); and 
ECOG Performance Status.  Laboratory tests for Screening including hematology, 
coagulation, and chemistry profile; urinalysis; and a pregnancy test for women of 
childbearing potential must be performed within 28 days prior to the first dose of  study 
treatment but maybe used as Cycle 1 Day 1 safety labs if done within 3 days of the first 
dose of study treatment.  Screening/Baseline tumor evaluations must be performed 28 
days prior to the first dose of study treatment.   
Results of all screening evaluations must be reviewed by the principal Investigator or 
his/her designee to ensure that all eligibility criteria have been satisfied prior to subject 

 
 
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enrollment.  Written informed consent must be obtained prior to the performance of any 
study specific Screening evaluations. 
8.3 
Study Cycle Evaluation 
Baseline imaging studies and tumor assessments must be performed within 28 days prior 
to the first ADXS11-001 infusion in the first Treatment Period.  Subsequent assessments 
will be conducted at Week 12 in Cycle 1, followed by assessment every 12 weeks 
(± 1 week) thereafter.  Apparent progression within the first 12 weeks not accompanied 
by clinical deterioration, should be confirmed 3 to 4 weeks later. 
Blood samples for immune monitoring and cytokine/chemokine analysis should be 
collected per schedule in Cycle 1 only (See Section 8.1 Study Procedures). 
A physical examination, an ECOG Performance Status, vital sign measurements, 
hematology and chemistry profiles, and urinalysis will be performed prior to each study 
treatment infusion and at the end of therapy.  Subjects will also be asked about the 
occurrence of any AEs and changes to concomitant medications. 
Vital signs (including blood pressure, pulse rate, respiratory rate, and temperature) will 
be checked and recorded prior to administration of ADXS11-001 and 
 
 following the infusion.  Weight will be collected prior to 
each ADXS11-001 infusion. 
A urine pregnancy test will be performed within 72 hours prior to each ADXS11-001 
infusion and at the end of therapy for all women of childbearing potential. 
8.4 
End of Therapy Evaluations 
End of therapy is not a visit.  It is a list of assessments that must be completed upon the 
decision to discontinue a subject from study treatment.  These evaluations include:  a 
physical examination, ECOG Performance Status, vital sign measurements, weight, 
hematology, coagulation, and chemistry profiles, urinalysis, and imaging studies, if 
indicated.  AEs and changes to concomitant medications will also be assessed and 
documented. 
8.5 
Safety Follow-Up/Post-Treatment Visits 
Safety follow-up will be conducted via a telephone call at 30 days (± 5 days) after the last 
ADXS11-001 infusion to confirm the resolution of any ongoing AEs and SAEs.  
Additional unscheduled visits may be considered as needed and at the discretion of the 
Investigator.  Safety follow-up will also continue to be monitored for AEs and SAEs 
during the 3-year Lm surveillance period of the study (see below). 
Surveillance monitoring for the detection of Lm will be initiated at the completion of 
study treatment according to the protocol or at the time of study discontinuation if earlier. 
This surveillance monitoring period will consist of a 6-month course of oral antibiotics, 
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obtaining a blood sample to monitor CBC, CMP, including CRP and ESR, and blood 
cultures at regular intervals.  This testing will be performed on all subjects who have 
received at least 1 dose of ADXS11-001.  It will occur every 3 months (±2 weeks) for 3 
years beginning after the last dose of study treatment.  If a persistent increase in CRP 
and/or ESR is observed with negative blood cultures for Listeria during this time, the 
subject should be evaluated and treated, as appropriate, for another possible cause.  In the 
event that a definite cause has not been identified, subjects must continue to be monitored 
closely, including additional testing and a blood culture, for possible signs/symptoms of 
listeriosis.  This testing may be performed at the investigational site or at another 
acceptable location following consultation with the Sponsor. 
9 EVALUATION CRITERIA 
9.1 
Safety 
The safety of ADXS11-001 administration will be assessed according to the NCI CTCAE 
v 4.03 criteria which will be used to define the grades and levels of toxicity.  These 
criteria will be applied to: 
 Observation of the infusion site for swelling, irritation, immune reaction or other 
abnormalities 
 Changes from baseline in physical examination findings and vital signs 
 Changes from baseline in laboratory parameters (hematology, coagulation, and serum 
chemistry) 
 Evidence of allergic and constitutional symptoms 
 Reported AEs 
Safety evaluations will be performed throughout the duration of the study.  All subjects 
who received at least 1 dose of ADXS11-001 will be evaluated for safety.  See 
Section 13.2, Collection of Safety Information, for the definition of an AE. 
9.1.1 
Baseline Tumor Assessments 
The baseline tumor burden (unidimensionally-measured or evaluable disease) will be 
assessed during the pretreatment evaluations.  The Investigator will identify 
prospectively, the lesions to be followed in order to evaluate the subject’s response to 
therapy (see Section 9.1.4, Definition of Target/Non-target Lesions).  Imaging areas will 
include the chest, abdomen, pelvis and other areas as indicated by clinical presentation. 
9.1.2 
Tumor Imaging and Assessment of Disease 
Computed tomography (CT) and magnetic resonance imaging (MRI) will be considered 
the best currently available and reproducible methods to measure target lesions (as 

 
 
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defined in Section 9.1.4, Definition of Target/Non-target Lesions) selected for response 
assessment.  Conventional CT should be performed with contiguous cuts of 10 mm or 
less.  Spiral CT scan should be performed using a 5 mm contiguous reconstruction 
algorithm (as a general rule, lesion diameter should be no less than double the slice 
thickness).  Lesions on chest x-rays will be acceptable as measurable lesions when they 
are clearly defined and surrounded by aerated lung; however, CT is preferable.  
Ultrasound is not an acceptable method to measure disease. 
Assessment of disease will be done using both RECIST 1.1 criteria and irRECIST 
criteria.  All subjects who have completed one 12-week cycle of ADXS11-001 treatment 
will be considered evaluable for response. 
9.1.3 
Measurable and Non-Measurable Lesions and Disease 
Measurable lesions will be those that can be accurately measured in at least one 
dimension with the longest diameter  2.0 cm (for spiral CT scan or MRI,  1.0 cm).  
Measurable disease will be present if the subject has one or more measurable lesions. 
Non-measurable lesions/disease will be all other lesions (or sites of disease), including 
small lesions (those with all measurements < 2.0 cm or < 1.0 cm with spiral CT/MRI), or 
any of the following:  bone lesions, leptomeningeal disease, ascites, pleural or pericardial 
effusion, inflammatory breast disease, lymphangitis, cutis/pulmonis, abdominal masses 
that are not confirmed and followed by imaging techniques, cystic lesions, and lesions 
occurring within a previously irradiated area unless they are documented as new lesions 
since the completion of radiation therapy. 
9.1.4 
Target/Non-Target Lesions 
All measurable lesions, up to a maximum of 2 lesions per organ and 5 lesions in total, 
should be identified as target lesions to be measured and recorded at baseline.  The target 
lesions should be representative of all involved organs.  Target lesions will be selected 
based on their size (the lesion with the longest diameter) and suitability for accurate 
repeated measurements.  At baseline, a sum of the longest diameters for all target lesions 
will be calculated and recorded as the baseline tumor burden.  The baseline sum will be 
used as the reference point to determine the objective tumor response of the target 
lesions. 
Measurable lesions other than the target lesions and all sites of non-measurable disease 
will be identified as non-target lesions and will be recorded at baseline.  Non-target 
lesions will be evaluated at the same assessment time points as target lesions. 
9.1.5 
Response in Measurable Lesions (RECIST 1.1) 
At baseline, the sum of the longest diameters (SumD) of all target lesions (up to 2 lesions 
per organ, up to 5 lesions total) is measured.  At each subsequent tumor assessment, the 
SumD of the target lesions and of new, measurable lesions (≥10; up to 2 new lesions per 

 
 
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organ, total 5 new lesions) are added together to provide the total measurable tumor 
burden (TMTB): 
TMTB = SumD target lesions + SumD new, measurable lesions 
Percentage changes in TMTB per assessment time point describe the size and growth 
kinetics of both old and new measurable lesions as they appear.  At each tumor 
assessment, the response in target and new measurable lesions is defined based on the 
change in TMTB. 
 Complete Response (CR): Disappearance of all target lesions.  Any pathological 
lymph nodes (whether target or non-target) must have reduction in short axis to 
<10 mm. 
 Partial Response (PR): At least a 30% decrease in the sum of diameters of target 
lesions, taking as reference the baseline sum diameters. 
 Progressive Disease (PD): At least a 20% increase in the sum of diameters of target 
lesions, taking as reference the smallest sum on study (this includes the baseline sum 
if that is the smallest on study).  In addition to the relative increase of 20%, the sum 
must also demonstrate an absolute increase of at least 5 mm.  (Note: the appearance 
of one or more new lesions is also considered progression). 
 Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while on 
study. 
9.1.6 
Immune-Related Response in Measurable Lesions (irRECIST) 
In addition to evaluation using RECIST 1.1 criteria, an immune response adaptation of 
RECIST will be applied to this trial.  The essential differences between irRECIST and 
RECIST criteria are as follows: 
 New measureable lesions do not necessarily constitute progressive disease and they 
should be added into the total tumor burden. New non-measurable lesions do not 
constitute disease progression but will prevent the determination of an irCR. 
 Apparent disease progression should be confirmed after 4 weeks in the absence of 
symptoms consistent with clinical deterioration. 
At baseline, the sum of the longest diameters (SumD) of all target lesions (up to 2 lesions 
per organ, up to total 5 lesions) is measured.  At each subsequent tumor assessment (TA), 
the SumD of the target lesions and of new, measurable lesions (≥ 10 mm [lymph nodes 
≥ 15 mm in shortest diameter]; up to 2 new lesions per organ, total 5 new lesions) are 
added together to provide the total measurable tumor burden (TMTB): 
TMTB = SumD target lesions + SumD new, measurable lesions 

 
 
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Percentage changes in TMTB per assessment time point describe the size and growth 
kinetics of both old and new, measurable lesions as they appear.  At each tumor 
assessment, the response in target and new, measurable lesions is defined based on the 
change in TMTB (after ruling out irPD) as follows: 
 Complete Response (irCR):  complete disappearance of all target and new, 
measurable lesions, with the exceptions of lymph nodes which must decrease to 
<10 mm in short axis 
 Partial Response (irPR):  decrease in TMTB ≥30% relative to baseline (see below) 
 Stable Disease (irSD):  not meeting criteria for irCR or irPR, in absence of irPD 
 Progressive Disease (irPD):  increase in TMTB ≥20% relative to nadir 
9.1.7 
Response in Non-Measurable Lesions (RECIST 1.1) 
While some non-target lesions may actually be measurable, they need not be measured 
and instead should be assessed only qualitatively. 
 Complete Response (CR): Disappearance of all non-target lesions and normalization 
of tumor marker level. All lymph nodes must be non-pathological in size (<10mm 
short axis). 
 Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance 
of tumor marker level above the normal limits. 
 Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 
(Note: the appearance of one or more new lesions is also considered progression). 
When the subject also has measurable disease, to achieve ‘unequivocal progression’ on 
the basis of non-target disease, there must be an overall level of substantial worsening in 
non-target disease such that, even in presence of SD or PR in target disease, the overall 
tumor burden has increased sufficiently to merit discontinuation of therapy. 
In the event that the subject has only non-measurable disease, the same general concepts 
apply as noted above, however, in this instance there is no measurable disease assessment 
to factor into the interpretation of an increase in non-measurable disease burden.  Because 
worsening in non-target disease cannot be easily quantified, a useful test that can be 
applied when assessing subjects for unequivocal progression is to consider if the increase 
in overall disease burden based on the change in non-measurable disease is comparable in 
magnitude to the increase that would be required to declare PD for measurable disease 
(i.e., an increase in tumor burden representing an additional 73% increase in ‘volume’ 
which is equivalent to a 20% increase diameter in a measurable lesion). 

 
 
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9.1.8 
Immune-Related Response in Non-Measurable Lesions 
At each tumor assessment, the presence of any new, non-measurable lesions is assessed.  
The presence of such lesions will rule out an overall response of irCR.  An increase in the 
size or number of new, non-measurable lesions does not necessarily imply an overall 
response of irPD; if these lesions become measurable (≥ 10 mm) at a subsequent tumor 
assessment, their measurement will at that point start to contribute to the TMTB. 
In addition, the response in non-target lesions is defined as follows: 
 Complete Response (irCR):  complete disappearance of all non-target lesions 
 Stable Disease (irSD):  non-target lesions are stable 
 Progressive Disease (irPD):  unequivocal increases in number or size of non-target 
lesions.  To achieve unequivocal progression of non-target lesions, there must be an 
overall level of substantial worsening of non-target disease that is of a magnitude that 
the treating physician would feel it is important to change therapy. 
NOTE:  Equivocal findings of progression of non-target lesions (e.g., small and 
uncertain new lesions; cystic changes or necrosis in existing lesions) should be 
considered irSD, and treatment may continue until the next scheduled assessment. 
9.1.9 
Overall Response 
Overall response will be determined based on RECIST 1.1 criteria and by irRECIST 
criteria (Table 6).  Overall response according to irRECIST is derived from the responses 
in measurable lesions (based on TMTB) and the presence of any non-measurable lesions. 
Table 6  Tumor Response Evaluation:  Comparison of RECIST 1.1 and 
irRECIST 
Criteria 
RECIST 1.1 
irRECIST 
New measurable 
lesions (≥ 10 mm) 
Always represents PD 
Incorporated into tumor burden 
New non-
measurable lesions 
(< 10 mm) 
Always represents PD 
Does not define progression but 
precludes irCR 
Non-Target lesions 
Changes contribute to defining BOR of 
CR, PR, SD, and PD 
Contribute to defining irCR 
(complete disappearance required) 
CR 
Disappearance of all lesions 
Disappearance of all lesions 
PR 
≥ 30% decrease in the sum of the longest 
diameter of all target lesions compared 
with baseline, in absence of new lesions 
or unequivocal progression of non-target 
lesions 
≥ 30% decrease in tumor burden 
compared with baseline 

 
 
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Criteria 
RECIST 1.1 
irRECIST 
SD 
Neither sufficient shrinkage to qualify for 
PR nor sufficient increase to qualify for 
PD, taking as reference the smallest sum 
diameters while on study 
Neither a 30% decrease in tumor 
burden compared with baseline nor a 
20% increase compared with nadir 
can be established 
PD 
At least 20% increase in sum of diameters 
of target lesions, taking as reference the 
smallest sum on study. In addition to the 
relative increase of 20%, the sum must 
also demonstrate an absolute increase of 
at least 5mm.  The appearance of one or 
more new lesions is also considered 
progression. 
At least 20% increase in tumor 
burden compared with nadir (at any 
single time point)a 
irRECIST = immune-related Response Evaluation Criteria in Solid Tumors;  BOR = best overall response;  CR = 
complete response; irCR = immune-related complete response; PD = progressive disease;  PR = partial response; SD 
= stable disease; 
a  Subjects with an initial finding of progressive disease (irPD) before or at the 12-week imaging assessment, but 
without rapid clinical deterioration, require confirmation of irPD with a second, consecutive scan obtained ≥ 4 
weeks from the initiation documentation.  Subjects will continue to receive study treatment until irPD is confirmed 
at this later time point.  Best overall response (BOR) will therefore include responses occurring at any time before 
disease progression and after early progression (i.e., within the first 12 weeks of the study). 
9.1.10 
Best Overall Response (RECIST 1.1) 
The best overall response is the best response recorded from the start of the study 
treatment until the end of treatment taking into account any requirement for confirmation.  
The subject’s best overall response assignment will depend on the findings of both target 
and non-target disease and will also take into consideration the appearance of new lesions 
(Table 7). 
Table 7  Best Overall Response (RECIST 1.1) 
Target Lesions 
Non-Target Lesions 
Overall Response 
Baseline (Index) and 
New Measurable Lesions 
Baseline Lesions 
Unequivocal New 
Lesions 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or NE 
No 
PR 
SD 
Non-PD or NE 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 

 
 
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Target Lesions 
Non-Target Lesions 
Overall Response 
Baseline (Index) and 
New Measurable Lesions 
Baseline Lesions 
Unequivocal New 
Lesions 
Any 
Any 
Yes 
PD 
CR = complete response; NE = not evaluable at a particular time point; PR = partial response; SD = stable disease; PD 
= progressive disease 
9.1.11 
Immune-Related Best Overall Response (irRECIST) 
The immune-related best overall response (irBOR) is the best irRC overall response over 
the study as a whole, recorded between the date of first dose until the last tumor 
assessment prior to subsequent therapy (including tumor resection surgery) for the 
individual subject in the study (Table 8).  As with the primary definitions of tumor 
response, early progression (i.e., irPD occurring prior to Week 12) will not preclude an 
irBOR of irCR, irPR or irSD resulting from the Week 12 assessment.  An assessment of 
irPD at or after Week 12 will preclude a subsequent irBOR of irCR, irPR or irSD.  
However, any post-progression clinical activity in subjects with irBOR of irPD may be 
summarized for exploratory purposes. 
Table 8  Immune-Related Best Overall Response (irBOR) 
Target Lesions 
Baseline (Index) and 
New Measurable Lesions 
Non-Target Lesionsa 
irRC Overall Response 
Total Measurable 
Tumor Burden 
Baseline Lesions 
Unequivocal New 
Lesions 
irCR 
irCR 
No 
irCR 
irCR 
irSD 
No 
irPR 
irPR 
irCR or irSD 
No 
irPR 
irSD 
irCR or irSD 
No 
irSD 
irPD 
Any 
Yes or No 
irPD 
Any 
Unequivocal Progression 
Yes or No 
irPD 
Any 
Any 
Yes 
irPD 
irCR = immune-related complete response; irPR = immune-related partial response; irSD = immune-related stable 
disease; irPD = immune-related progressive disease 
a Any increase in the size or number of non-measurable lesions does not necessarily imply an overall response of 
irPD.  If these lesions become measurable (≥10 mm) at a subsequent assessment, their measurement will at that point 
start to contribute to the total measurable tumor burden.  To achieve unequivocal progression of non-target lesions, 
there must be substantial worsening in non-target disease that is of a magnitude that the Investigator feels it is 
important to change therapy.  Equivocal findings of progression of non-target lesions (e.g., small and uncertain new 
lesions; cystic changes or necrosis in existing lesions) should be considered irSD, and treatment may continue until 
the next assessment. 

 
 
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9.1.12 
Treatment after Initial Evidence of Radiologic Disease 
Progression 
Immunotherapy may produce antitumor effects by potentiating endogenous cancer-
specific immune response.  The response patterns seen with such an approach may extend 
beyond the typical time course of responses seen with cytotoxic agents and can manifest 
as a clinical response after an initial increase on tumor burden or even the appearance of 
new lesions.  If radiological imaging shows PD, subjects may continue on study with the 
option of continuing treatment, provided there is: 
 No deterioration in ECOG performance status 
 Absence of signs and symptoms (including worsening of laboratory values) indicating 
disease progression 
 Absence of rapid progression of disease 
 Absence of progressive tumor at critical anatomical sites (e.g., cord compression) 
requiring urgent alternative medical intervention 
Tumor assessment should be repeated ≥4 weeks later to confirm PD.  If repeat imaging 
shows a reduction of in the tumor burden demonstrating CR, PR or SD compared to the 
initial scan, treatments may be continued or resumed.  If repeat imaging shows continued 
progression of disease, subjects will be discontinued from study therapy, unless the basis 
for the PD assessment is enlarged tumor-draining lymph nodes in the presence of a target 
tumor reduction.  In determining whether or not tumor burden has increased or decreased, 
investigators should consider all target lesions as well as non-target lesions.  If the repeat 
imaging confirms initially documented PD but shows no evidence of further tumor 
progression, subjects should be discontinued from the study treatment.   
10 INVESTIGATIONAL DRUG PRODUCT 
The Investigator shall take responsibility for and shall take all steps to maintain 
appropriate records and ensure appropriate supply, storage, handling, distribution and 
usage of investigational product in accordance with the protocol and any applicable laws 
and regulations.   
ADXS11-001 will be supplied free of charge by Advaxis, Inc. 
10.1 Packaging and Labeling 
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.  
This trial is open-label; therefore, the subject, the trial site personnel, the sponsor and/or 
designee are not blinded to treatment.  Drug identity (name, strength) is included in the 
label text; random code/disclosure envelopes or lists are not provided. 

 
 
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10.1.1 
Storage and Handling Requirements 
Clinical supplies must be stored in a secure, limited-access location under the storage 
conditions specified on the label. 
Receipt and dispensing of trial medication must be recorded by an authorized person at 
the trial site. 
Clinical supplies may not be used for any purpose other than that stated in the protocol. 
10.1.2 
Returns and Reconciliation 
The Investigator is responsible for keeping accurate records of the clinical supplies 
received from Advaxis or designee, the amount dispensed to subjects and the amount 
remaining at the conclusion of the trial. 
Upon completion or termination of the study, all unused and/or partially used 
investigational product will be destroyed at the site per institutional policy.   
10.1.3 
Destruction of ADXS11-001 
It will be the investigator’s responsibility to arrange for disposal of all empty containers, 
provided that procedures for proper disposal have been established according to 
applicable federal, state, and local regulations and institutional guidelines and procedures, 
and provided that appropriate records of disposal are kept. 
 
 
 
 
 
 
If ADXS11-001 is destroyed at the site, it will be the investigator’s responsibility to 
ensure that procedures for proper disposal have been established according to applicable 
regulations, guidelines, and institutional procedures and that: 
 Written authorization for disposal/destruction has been granted by Advaxis 
 Arrangements have been made for the disposal 
 Appropriate records of the disposal have been documented 
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10.2 ADXS11-001 Records at Investigational Site 
It will be the responsibility of the Investigator to ensure that a current record of ADXS11-
001 disposition is maintained at each study site where ADXS11-001 is inventoried and 
disposed.  Records or logs must comply with applicable regulations and guidelines, and 
should minimally include: 
 The amount received and placed in storage area 
 The amount currently in storage area 
 The label identification, lot, or batch number 
 Dates and initials of person responsible for each ADXS11-001 inventory 
entry/movement 
 The amount dispensed to and returned by each subject, including unique subject 
identifiers 
 The amount transferred to another area for dispensing or storage 
 Non-study disposition (e.g., lost, wasted, broken) 
 The amount destroyed at study site, if applicable 
10.2.1 
Safety Precautions 
ADXS11-001 is a live attenuated strain of Listeria monocytogenes (Lm) that has been 
attenuated such that it is cleared by severe combined immunodeficiency (SCID) mice 
lacking cellular immunity and gamma interferon knock-out mice lacking adaptive 
immunity.  It has also been altered such that it is impossible for it to recombine with 
wild-type Lm.  
 
 
 
Wild type Listeria is Gram-positive, non-spore-forming, facultative bacilli that are 
hemolytic and catalase-positive. It is a naturally occurring bacterium that is present in the 
environment and is known to cause illness in some people when they eat foods 
contaminated with Lm. Although healthy adults and children can contract a wild-type 
Listeria infection, they do not usually become seriously ill.  People at risk of severe 
illness from wild-type Listeria are pregnant women, newborns, and persons with 
impaired immune function. 
Even though ADXS11-001 is non-pathogenic, all Lm species are classified as 
 
 according to the BMBL 5th Edition.  Universal precautions and 
institutional guidelines should be used when handling investigational drugs and human 
specimens.  Except for the transmission of mother to fetus, human-to-human transmission 
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of Lm is not known to occur.[19]  Shedding studies completed in Phase 1 demonstrated 
that, in the absence of antibiotics, ADXS11-001 was rapidly cleared from the blood with 
no Lm detected in the blood of any subject beyond 48 hours post-dosing, and no Lm was 
detected in the urine and feces in any subject at the highest dose of ADXS11-001 tested 
(1 x 1010 CFU) [11]. 
Based on the mechanism of action of ADXS11-001 and the inability of Lm to be 
transferred from human-to-human, there is no need for subjects who receive ADXS11-
001 to avoid contact with people who are elderly, pregnant, newborns, or have weakened 
immune systems. 
Precautions as stated in the BMBL 5th Edition include: 
Wild-type L. monocytogenes poses a potential hazard to laboratory 
personnel.  The Gram-positive, non-spore-forming, aerobic bacilli are 
hemolytic and catalase-positive. Bacteria have been isolated from soil, 
dust, human food, animals, and asymptomatic humans. Most cases of 
listeriosis have arisen from eating contaminated food products, most 
notably soft cheeses, raw meat, and unwashed raw vegetables.  Although 
healthy adults and children can contract a Listeria infection, they do not 
usually become seriously ill. At risk of severe illness are pregnant 
women, newborns, and persons with impaired immune function. 
Laboratory Hazards:  Wild-type Lm may be ubiquitous in the environment 
and may be found in feces, cerebrospinal fluid (CSF), and blood, as well 
as food and environmental materials.  Ingestion is the most common mode 
of exposure, but wild-type Listeria can also cause eye and skin infections 
following a direct exposure.  Wild-type Lm infections in pregnant women 
occur most often in the third trimester and may precipitate labor.  
Transplacental transmission of Lm poses a grave risk to the fetus and may 
result in disseminated abscesses contributing to a mortality rate of nearly 
100%. 
Recommended Precautions:  
 practices, containment equipment, 
and facilities are recommended for activities with clinical specimens and 
cultures known or suspected to contain the agent.  Biopsy specimens must 
be fixed immediately by dropping the specimen in formaldehyde solution. 
Gloves and eye protection should be worn while handling the agent.  
Pregnant women who work with Listeria monocytogenes in the clinical or 
research laboratory setting should be fully informed of the potential 
hazards associated with the organism, including potential risks to the 
fetus. 
 
 
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11 CLINICAL SAFETY MANAGEMENT 
11.1 ADXS11-001 Pretreatment Prophylaxis Regimen 
Mild to moderate flu-like symptoms and cytokine release symptoms (e.g., constitutional 
symptoms such as fever, chills, rigors, fatigue, headache, nausea, vomiting, tachycardia, 
shortness of breath, hypotension and rash) are commonly seen and typically occur 
2-4 hours after ADXS11-001 infusion and often resolve within 12-24 hours.  
Prophylactic medications are intended to reduce the inflammatory response.  Subjects 
should receive the following pretreatment prophylaxis regimen.  
IV Fluid Hydration: 
 Normal saline (e.g., 500 mL over 30 minutes) 
Premedication Regimen: 
 Antihistamine – PO or IV (e.g. diphenhydramine 25 mg or equivalent),  once 
 NSAIDs - PO (e.g., naproxen 220 mg or ibuprofen, 400 mg), once 
 Antiemetic - PO or IV (e.g., promethazine or ondansetron), once 
 Histamine H2-receptor antagonist – PO or IV (e.g., famotidine 20 mg or equivalent), 
once 
Pretreatment medication should be given on the day of dosing and completed at least 
prior to the start of the assigned study treatment.  Additional NSAID doses 
and antiemetic administration should be given per label or package insert post initial 
administration on Day 1 and Day 2, as needed.  The prescribed dosage of the selected 
NSAID and antiemetic will be at the discretion of the Investigator. 
Do not substitute acetaminophen for the selected NSAID for prophylactic treatment since 
acetaminophen does not have similar anti-inflammatory properties that could ameliorate 
cytokine release symptoms. 
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11.2 Step-Up Regimen for ADXS11-001 Pre-Dose Treatment Prophylaxis 
Antiemetics such as promethazine or ondansetron will continue to be given as described 
above in Section 11.1.  Thus, subjects will leave the study site with doses of the NSAID 
and antiemetic to take later in the day, as appropriate. 
11.3 Administration of ADXS11-001 
  
 
 
 
 
 
11.4 Supportive Care Guidelines 
 
 
 
 
 
 
 
11.4.1 
Cytokine Release Symptoms 
Cytokine release symptoms are a constellation of inflammatory symptoms resulting from 
cytokine elevations associated with T cell engagement and proliferation.  Symptoms 
related to cytokine release may include constitutional symptoms such as fever, chills, 
rigors, fatigue, headache, nausea, vomiting, rash, tachycardia, hypotension and shortness 
of breath which usually presents several hours after the infusion and lasts for up to 
24 hours.  These symptoms are caused by an increase in cytokines such as TNFα, IFNγ 
and IL-6, all of which have been shown to occur after ADXS11-001 administration, 
resulting from the body’s immune response to the therapy.  Although, symptoms are 
often Grade 1-2 and transient, resolving with symptomatic management within 
30 minutes to 1 hour, in rare instances (~1%) Grade 3-4 hypotension has been seen.  
Therefore, close monitoring of blood pressure is strongly recommended at baseline, and 
during the post-infusion period.  Increased levels of IL-6have been strongly associated 
with capillary leak which manifests as hypotension due to the cytokines involved.  We 
have observed elevated IL-6 levels after infusion of ADXS11-001, with peak levels 
occurring 2-4 hours after infusion.  Emerging evidence indicates that IL-6 antagonists, 
such as tocilizumab, have demonstrated good results in treating cytokine-induced 
hypotension [20-23] and are therefore recommended for cases of severe hypotension 
refractory to supportive care (e.g., fluids and/or pressors). 
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The management of cytokine release symptoms and guidelines for subsequent treatment 
for subjects who have experienced these AEs are shown in Table 9. 

 
 
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Table 9  Recommended Management Guidelines for Adverse Events Associated with Cytokine Release 
Toxicity 
NCI 
CTCAE 
Grade or 
Severity 
Treatment 
Modification for Subsequent infusions 
Hypotension 
1 
Mild 
 
Supportive care 
 Increase pretreatment IV fluids (e.g., 500 ml -1L 
normal saline) 
All other cytokine release 
symptoms (e.g. chills, rigors, 
fever, nausea, vomiting) 
1 
 
Supportive care 
 No modification 
Hypotension 
 
2 
Moderate 
 
Fluids and 1 dose of pressor (e.g. 0.3 mg 
epinephrine IM)  
 
Increase monitoring of vital signs 
 
If hypotension persist for more than one hour 
consider low dose corticosteroids (e.g. 
hydrocortisone 100 mg IV over 30 seconds 
 Extend infusion time to 2 hours.  
 Increase pretreatment IV fluids (e.g. 500 ml -1L 
normal saline)  
 Incorporate Glucocorticoid- Hydrocortisone or 
equivalent- 50 mg, IV, as premedication 
 
All other cytokine release 
symptoms (e.g. chills, rigors, 
fever, nausea, vomiting) 
2 
 
Appropriate supportive care measure 
 Extend infusion time to 2 hours.  
 Consider increasing doses of prophylactic medications 
Hypotension 
3 
Severe 
 
Fluids, high dose pressors (e.g. Dopamine 10 
µg/kg/min)  +1 dose tocilizumab*(4mg/kg over 
1 hour) 
 
If hypotension worsens or is unresponsive to 
above measures, administer corticosteroids 
 
If the subject’s condition does not improve or 
stabilize within 24 hours of the tocilizumab 
dose, administration of a second dose of 
tocilizumab +/- corticosteroids should be 
considered. 
 Discuss with Sponsor 

 
 
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Toxicity 
NCI 
CTCAE 
Grade or 
Severity 
Treatment 
Modification for Subsequent infusions 
All other cytokine release 
symptoms (e.g. chills, rigors, 
fever, nausea, vomiting) 
3 
 
Appropriate supportive care  measures 
 Extend infusion time to 2 hours.  
 Consider increasing doses of prophylactic dose of 
NSAID, or antiemetic as appropriate 
Hypotension/ 
Organ toxicity, mechanical 
ventilation 
4 
Life 
threatening 
 
Vigilant supportive care 
 
Fluids 
 
High dose  pressors,  
 
Tocilizumab (4mg/kg over 1 hour) +/- 
corticosteroids (hydrocortisone 100 mg IV 
infused over 30 seconds administered every 2 
hours until symptoms resolve to <Grade 1) 
 Permanently discontinue 
* Tocilizumab is a humanized, immunoglobulin G1k (IgG1k) anti-human IL-6R mAb approved for treatment of adult subjects with moderately to severely active rheumatoid 
arthritis (RA) who have had an inadequate response to Disease-Modifying Anti-Rheumatic Drugs (DMARDs), for the treatment of active polyarticular juvenile idiopathic arthritis 
(PJIA), and active systemic juvenile idiopathic arthritis (SJIA) in subjects 2 years of age and older.  Tocilizumab works by preventing IL-6 binding to both cell-associated and 
soluble IL-6Rs. Although, it is not indicated for the treatment of cytokine release symptoms emerging clinical experience at several institutions has concluded that tocilizumab is an 
effective treatment for severe or life-threatening cytokine release symptoms.[20-23] 

 
 
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11.4.2 
Nausea/vomiting 
Nausea and vomiting should be treated aggressively.  In addition to the prophylactic 
antiemetic therapy subjects receive prior to each infusion, consideration should be given 
to subsequent administration of antiemetic therapy every 8 hours, as needed according to 
standard institutional practice.  Subjects should also be strongly encouraged to maintain 
liberal oral fluid intake. 
11.5 Management of Infusion Reactions 
While there is some overlap between infusion reactions symptoms and cytokine release 
symptoms, infusion reactions symptoms typically occur during the infusion, while 
cytokine release symptoms typically occur after the infusion and are mediated by a 
different mechanism of action.  Signs/symptoms of infusion reactions may include: 
allergic reaction/hypersensitivity (including drug fever); arthralgia (joint pain); 
bronchospasm; cough; dizziness; dyspnea (shortness of breath); fatigue (asthenia, 
lethargy, malaise); headache; hypertension; hypotension; myalgia (muscle pain); nausea; 
pruritic/itching; rash/ desquamation; rigors/chills; sweating (diaphoresis); tachycardia; 
tumor pain (onset or exacerbation of tumor pain due to treatment); urticaria (hives, welts, 
wheals); and vomiting.  
Table 10 below shows the management guidelines for subjects who experience an 
infusion reaction associated with administration of ADXS11-001. 

 
 
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Table 10  Recommended Management Guidelines for Infusion Reactions 
NCI CTCAE Grade 
Management 
Grade 1 
 
Mild reaction; infusion interruption 
not indicated; intervention not 
indicated 
Increase monitoring of vital signs as medically indicated until the 
subject is deemed medically stable in the opinion of the 
Investigator. 
Grade 2 
 
Requires infusion interruption but 
responds promptly to symptomatic 
treatment (e.g., antihistamines, 
NSAIDS, narcotics, IV fluids); 
prophylactic medications indicated 
for ≤24 hrs. 
1. Stop Infusion and monitor symptoms. 
Additional appropriate medical therapy may include but is not 
limited to: 
IV fluids 
Antihistamines 
NSAIDS 
Acetaminophen 
Narcotics 
2. Increase monitoring of vital signs as medically indicated until 
the subject is deemed medically stable in the opinion of the 
Investigator. 
If symptoms resolve within one hour of stopping drug 
infusion, the infusion may be restarted at 50% of the original 
infusion rate.  Otherwise dosing will be held until symptoms 
resolve and the subject should be premedicated for the next 
scheduled dose. 
Grades 3 or 4 
 
Grade 3: 
Prolonged (i.e., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms following 
initial improvement; 
hospitalization indicated for other 
clinical sequelae (e.g., renal 
impairment, pulmonary infiltrates) 
 
Grade 4: 
Life-threatening; pressor or 
ventilatory support indicated 
3. Stop Infusion. 
Additional appropriate medical therapy may include but is not 
limited to: 
IV fluids 
Antihistamines 
NSAIDS 
Acetaminophen 
Narcotics 
Oxygen 
Pressors 
Corticosteroids 
Epinephrine 
4. Increase monitoring of vital signs as medically indicated until 
the subject is deemed medically stable in the opinion of the 
Investigator. 
5. Hospitalization may be indicated. 
6. Subjects who experience a Grade 4 reaction should be 
permanently discontinued from study. Subjects who 
experience a grade 3 reaction may be discontinued. 
Discussion with the Sponsor is recommended 
11.5.1 
Listeriosis and Listeria Infection - Identification and Management 
A person with (wt) listeriosis usually presents with fever and muscle aches, sometimes 
preceded by diarrhea or other gastrointestinal symptoms.  Almost everyone who is 
diagnosed with listeriosis has an "invasive" infection, in which the bacteria spread 

 
 
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beyond the gastrointestinal tract.  The symptoms vary with the infected person.  Pregnant 
women typically experience fever and other non-specific symptoms, such as fatigue and 
aches.  However, infections during pregnancy can lead to miscarriage, stillbirth, 
premature delivery, or life-threatening infection of the newborn.  In people other than 
pregnant women, symptoms can include headache, stiff neck, confusion, loss of balance, 
and convulsions in addition to fever and muscle aches.  Listeriosis can present in 
different ways.  In older adults and people with immunocompromising conditions, 
septicemia and meningitis are the most common clinical presentations.[24]  Subjects may 
need immediate evaluation with a brain CT scan or MRI and a lumbar puncture with the 
analysis of spinal fluid to rule out meningitis. 
For symptomatic subjects, diagnosis is confirmed only after isolation of Lm from a 
normally sterile site, such as blood or spinal fluid (in the setting of nervous system 
involvement), or amniotic fluid/placenta (in the setting of pregnancy).  Stool samples are 
of limited use and are not recommended.  Lm can be isolated readily on routine media, 
but care must be taken to distinguish this organism from other Gram-positive rods, 
particularly diphtheroids.  Selective enrichment media improve rates of isolation from 
contaminated specimens.  You can expect that the cultures will take approximately 1-2 
days for growth.  Importantly, a negative culture does not rule out infection in the 
presence of strong clinical suspicion.  Serological tests are unreliable, and not 
recommended at the present time [24]. 
Listeriosis is treated with a wide range of antibiotics.  In preclinical studies, wt-Lm and 
ADXS11-001 are susceptible to the lowest tested concentration of the following 
antimicrobial agents:  
 
 
  
11.5.2 
Management and Surveillance of Listeria during Study 
Participation 
 
In the event a subject experiences a persistent fever lasting 72 hours after receiving study 
treatment then the oral antibiotic regimen will be replaced by broad spectrum IV 
antibiotic treatment.  If symptoms consistent with sepsis occur close to ADXS11-001 
administration or at any time after ADXS11-001 administration, immediate medical 
attention must be sought.  A microbial culture will be taken to identify the agent of sepsis 
and antibiotic sensitivity testing should be performed to confirm susceptibility.  An 
infectious disease consult should be obtained for further management of these subjects. 
All subjects will receive a 6-month course of an oral antibiotic regimen as a prophylactic 
measure following the completion of the last dose of ADXS11-001 treatment or at the 
time of study discontinuation.  This additional safety measure is intended to eradicate Lm 
from the body. 
Lm surveillance monitoring will also be initiated following the completion of the last 
dose of ADXS11-001 treatment or at the time of study discontinuation. This monitoring 
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will include obtaining a blood sample for CBC, comprehensive metabolic panel (CMP), 
including CRP and ESR, and blood cultures for the detection of Listeria.  Testing will be 
performed on all subjects who have received at least 1 dose of ADXS11-001 and occur 
every 3 months (±2 weeks) for 3 years. 
Should a diagnosis of listeriosis be made at any point after treatment with ADXS11-001 
and the 6-month course of oral antibiotics are completed, immediate and intensive IV 
antibiotic treatment (ampicillin +/- gentamycin or other IV antibiotic regimen as 
indicated) is required  An infectious disease consult should be obtained.  Based on each 
individual subject’s case and at the discretion of the treating physician, the removal of 
any foreign medical object that has been present since treatment with ADXS11-001 was 
initiated may be warranted.  It is extremely important that the Investigator, his/her 
research staff, other healthcare providers involved in the care of the subject as well as 
each subject participating in this study are educated and made aware of the signs and 
symptoms of listeriosis and the potential for delayed listeremia/listeriosis.  Educational 
materials for the Investigator, research staff, health care providers and subjects will be 
prepared and educational training performed.  
11.6 ADXS11-001 Toxicities and Treatment 
Please refer to Section 3.4.1 for summary information on the ADXS11-001 AE profile. 
ADXS11-001 is a live attenuated bioengineered nonpathogenic strain of Lm, and one that 
is known to stimulate a strong innate immune response characterized by high levels of 
cytokine release from immune cells into the general circulation.  This pattern of side 
effects is consistent with other immunotherapy agents. 
The most likely AEs associated with ADXS11-001 are comprised primarily of individual 
flu-like symptoms (e.g., fever, chills, body ache, and fatigue) or cytokine release 
symptoms (e.g., headache, nausea, vomiting, tachycardia, shortness of breath, 
hypotension and rash).  The symptoms usually present within 2-4 hours after the 
completion of infusions and are often mild to moderate and transient in nature or respond 
quickly to symptomatic treatment.  In rare instances they may last up to 24 hours.  No 
cumulative or delayed toxicity has been observed. 
Less likely AE’s include increase heart rate, low blood pressure, muscle aches, 
headaches, allergic reaction, changes in blood chemistry, changes in blood counts, and 
short term changes in liver function. 
Rare but serious AEs include high fever and difficulty breathing and hypotension. 
, ADXS11-001 has a tropism for the liver.  Transient asymptomatic 
elevations of ALT and alkaline phosphatase were observed after dosing in the Phase 1 
trial without prophylactic medication administration.  For that reason, subjects with 
significant liver disease are excluded, and particular attention is to be paid to hepatic 
abnormalities. 
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Please reference the ADXS11-001 IB for complete information regarding AEs. 
During the time the subjects are at the study site, the infusion line will be left in place to 
administer parenteral drugs, should that be necessary.  As described in Section 11, 
subjects will be pretreated to minimize side effects of the study agent.  The Investigator 
should observe the subjects for signs of inflammation and/or infection, including 
unremitting fever or vomiting, that require more intense therapy, and to treat them 
appropriately.  All such treatments are to be listed on the eCRF. 
11.6.1 
Treatment Modification Guidelines 
The dose of ADXS11-001 will not be modified (e.g., reduced or increased).  However, 
treatment may be delayed or discontinued for drug related severe and life-threating 
toxicities, as shown below in Table 11. 
Table 11  Treatment Delay/Discontinuation Guidelines for Drug-Related 
Adverse Events 
Toxicity 
Grade 
Hold treatment 
Timing for 
restarting treatment 
Discontinue 
Treatment 
Hematologic 
1,2,3 
No  
N/A 
N/A 
4 
Yes 
Toxicity resolves to 
≤Grade 1 or baseline 
Toxicity does not 
resolve to ≤Grade 1 
or baseline within 12 
weeks 
Non-
hematologic, 
excluding 
cytokine 
release 
symptoms 
and DLTs 
1 
No 
N/A 
N/A 
2-3 
Yes 
Toxicity resolves to 
≤Grade 1 
Toxicity not 
resolved to ≤Grade 1 
within 12 weeks of 
last infusiona 
4 
N/A 
Permanent treatment 
discontinuation 
Permanent 
Discontinuation 
from Treatment 
a With investigator and sponsor agreement, subjects with a non-hematologic  AE (e.g. alopecia, neuropathy) still at 
grade 2 after 12 weeks, may continue treatment if only asymptomatic and controlled.  
 
11.6.2 
ADXS11-001 Treatment Alterations 
Subjects who experience a DLT during the dose escalation portion of the study or 
experience events described as a DLT in any subsequent treatment cycle will be 
discontinued from study treatment.  However, if the subject who experienced a DLT 
shows significant response to ADXS11-001, they may be eligible to receive ADXS11-
001 at a lower dose level for subsequent doses and cycles following discussion and 
agreement between the Investigator and Sponsor.  See Section 6.1 Dose Limiting 
Toxicity Criteria for definition of DLT. 

 
 
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11.7 Major and Minor Surgeries and ADXS11-001 Treatment 
No formal studies of the effect of ADXS11-001 on wound healing have been conducted.  
However, based on its mechanism of action it is not expected that administration of 
ADXS11-001 would complicate wound healing.  Therefore, a subject may initiate or 
resume study treatment 2 weeks after minor surgery (i.e., surgery involving little risk to 
the life of the subject; specifically an operation on the superficial structures of the body 
or a manipulative procedure that does not involve a serious risk) if the wound has 
completely healed and there are no wound healing complications.  A subject who has 
wound healing complications following minor surgery, received major surgery or 
requires new implants and/or devices (permitted by the protocol) during the course of the 
study, must wait a minimum of 6 weeks and must have recovered from any toxicity 
(e.g., return to baseline or Grade 1) and/or complication before the next infusion of study 
treatment.  Sponsor consultation is required prior to resuming study treatment for these 
subjects.  If the treatment is delayed due to concomitant surgery beyond 12 weeks, the 
subject may be discontinued from the study. 
11.8 Discontinuation of Study Subjects 
11.8.1 
Subject Study Discontinuation Criteria 
Subjects may withdraw consent at any time for any reason or be discontinued from the 
trial at the discretion of the investigator, should any untoward effect occur.  In addition, a 
subject may be withdrawn by the investigator or the sponsor if enrollment into the trial is 
inappropriate, the trial plan is violated, or for administrative and/or other safety reasons. 
A subject may be discontinued from the trial for any of the following reasons: 
 Screen Failure 
 AE/SAE 
 Lost to Follow-Up 
 Disease Progression 
 Death 
 Withdrawal of Consent by Subject 
 Investigator Decision/Study Non-Compliance by Subject 
 Achieved Complete Remission  
 Completed Study (at least 24 months of study treatment) 
 Other (specify) 

 
 
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In all cases, the reason for and date of withdrawal must be recorded in the eCRF and in 
the subject’s medical records.  The subject must be followed up to establish whether the 
reason was an AE, and, if so, this must be reported. 
When a subject discontinues/withdraws prior to study completion, all applicable activities 
scheduled for the final assessment (End of Therapy assessments) should be performed at 
the time of discontinuation.  Any AEs that are present at the time of 
discontinuation/withdrawal should be followed in accordance with the safety 
requirements outlined in Section 13.2 Collection of Safety Information.   
The Investigator must make every effort to contact subjects who discontinue the study 
prematurely or are lost to follow-up and to schedule the end of therapy assessments.  
Attempts to contact such subjects must be documented in the subject’s records (e.g., 
times and dates of attempted telephone contact, receipt for sending a registered letter). 
11.8.2 
Suspension or Discontinuation of the Study 
The occurrence of any Grade 4 (life threatening) toxicity may result in the temporary 
suspension of the study to evaluate available safety information to justify continued 
enrollment of subjects into the study.  
The study may be stopped at the study center at any time by the investigator.  Advaxis 
may stop the study (and/or the study center) for any reason.   
12 CONCURRENT THERAPIES AND PROCEDURES 
All prescription and nonprescription medication (excluding vitamins, nutritional 
supplements and hormone replacement therapy) taken by the subject from 30 days prior 
to screening and up to and including completion of the 3-year Lm surveillance period will 
be recorded in the medical record and on the eCRF.  Any addition, deletion, or change in 
the dose of these medications will also be recorded.  Generic names should be used to 
eliminate confusion that may result from trade names.  Protocol-mandated prophylactic 
medications, antibiotics and procedures administered/performed following the 
completion of study treatment, including during the 3-year Lm surveillance period, 
should also be captured in the eCRF.  
Study subjects should be reminded that acetaminophen should not be used for 
pretreatment prophylaxis associated with the foreseeable AEs related to the study 
treatment since this medication can interfere with treatment. 
Medications specifically prohibited in the exclusion criteria are not allowed during the 
ongoing trial.  If there is a clinical indication for one of these or other medications 
specifically prohibited during the trial, discontinuation from trial therapy may be 
required.  The Investigator should discuss any questions regarding this with the Sponsor.  
The final decision on any supportive therapy rests with the Investigator and/or the 
subject’s primary physician.  However, the decision to continue the subject’s on-trial 
therapy requires the mutual agreement of the Investigator, the Sponsor, and the subject.   

 
 
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Subjects are prohibited from receiving the following therapies during the screening and 
treatment phases (including retreatment for post-complete response relapse) of this trial: 
 Anti-cancer systemic chemotherapy or biological therapy 
 Surgical treatment as per consultation with the sponsor 
 PI3K and TNF inhibitors  
 Immunotherapy not specified in this protocol 
 Investigational agents other than ADXS11-001 
 Radiation therapy (except palliative radiation therapy for disease-related pain with a 
consult with the sponsor's medical monitor) 
 Live vaccines within 30 days prior to the first dose of trial treatment and while 
participating in the trial.  Examples of live vaccines include, but are not limited to, the 
following:  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. 
 Acetaminophen is not to be used for premedication but may be used for supportive 
care measures. NSAIDs, such as naproxen and ibuprofen have been evaluated and are 
confirmed not to interfere with efficacy. 
Subjects who, in the assessment by the Investigator, require the use of any of the 
aforementioned treatments for clinical management should be removed from the trial.  
Subjects may receive other medications that the Investigator deems to be medically 
necessary. 
13 ADVERSE EVENT REPORTING IN CLINICAL TRIALS 
13.1 Importance of Adverse Event Reporting 
Timely and complete reporting of safety information assists Advaxis in identifying any 
untoward medical occurrence, thereby allowing:  (1) the protection of the safety of study 
subjects, (2) a greater understanding of the overall safety profile of ADXS11-001, (3) 
recognition of dose-related ADXS11-001 toxicities, (4) appropriate modification of study 
protocols, (5) improvements in study design or procedures, and (6) adherence to 
worldwide regulatory requirements. 
AEs will be reported to FDA according to 21 CFR 312.32. 

 
 
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13.2 Collection of Safety Information 
An AE is defined as any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment.  An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of a medicinal product 
or protocol-specified procedure, whether or not considered related to the medicinal 
product or protocol-specified procedure.  Any worsening (i.e., any clinically significant 
adverse change in frequency and/or intensity) of a preexisting condition that is temporally 
associated with the use of the sponsor’s product, is also an AE. 
The Sponsor’s product includes any pharmaceutical product, biological product, device, 
diagnostic agent or protocol-specified procedure, whether investigational (including 
placebo or active comparator medication) or marketed, manufactured by, licensed by, 
provided by or distributed by Advaxis for human use. 
During clinical trials, AEs can be spontaneously reported or elicited during open-ended 
questioning, examination, or evaluation of a subject.  In order to prevent reporting bias, 
subjects should not be questioned regarding the specific occurrence of 1 or more AEs. 
AEs may occur during the course of the use of Advaxis’ product in clinical trials or 
within the follow-up period specified by the protocol, or prescribed in clinical practice, 
from overdose (whether accidental or intentional), from abuse and from withdrawal. 
AEs may also occur in screened subjects during any pre-allocation baseline period as a 
result of a protocol-specified intervention, including washout or discontinuation of usual 
therapy, diet, placebo treatment or a procedure. 
All AEs will be recorded from the time the consent form is signed through 30 days 
following cessation of treatment during the study treatment period of the study. AEs and 
SAEs will be recorded during the 3-year Lm surveillance period of the study and at each 
examination on the AE eCRF.  The reporting timeframe for AEs meeting any serious 
criteria is described in Section 13.7.1. 
Disease progression associated with the underlying malignancy need not be reported as 
an “adverse event”, per se.  Naturally, it is captured as a part of the intended endpoints. 
If known, the diagnosis of the underlying illness or disorder should be recorded, rather 
than its individual symptoms.  The following information should be captured for all AEs:  
onset and end dates, severity (grade of the event), Investigator’s opinion of the 
relationship to ADXS11-001 (see definitions below), treatment/action required for the 
AE, and information regarding resolution/outcome. 
AEs and other symptoms will be graded according to the expanded NCI CTCAE v 4.03.  
For AEs not contained within the toxicity criteria, the principal Investigator will be 
responsible for assessing the severity of an AE on the basis of the jeopardy to the 

 
 
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subject’s health and well-being and the ability of the subject to function during the event.  
These AEs will be graded as mild, moderate, or severe. 
The following categories and definitions of causal relationship to ADXS11-001 should be 
used for all Advaxis clinical trial AEs: 
 Definite:  there is a reasonable causal relationship between ADXS11-001 and the AE; 
the event responds to withdrawal of ADXS11-001 (dechallenge) and recurs with 
rechallenge when clinically feasible 
 Probable:  there is a reasonable causal relationship between study treatment and the 
AE; the event responds to dechallenge; rechallenge is not required 
 Possible:  there is a reasonable causal relationship between ADXS11-001 and the AE; 
the event responds to dechallenge or dechallenge information is lacking or unclear; 
rechallenge is not required 
 Unlikely:  There is a temporal relationship to investigational product administration, 
but there is not a reasonable causal relationship between the investigational product 
and the AE 
 Unrelated:  there is not a temporal relationship to ADXS11-001 administration (too 
early, late, or ADXS11-001 not taken) or there is a reasonable causal relationship 
between another drug, concurrent disease, or circumstance and the AE 
13.3 Adverse Event Follow-Up 
AEs and SAEs related to ADXS11-001 (definitely or possibly) should be followed to 
resolution or stabilization and reported as SAEs if they become serious.  This also applies 
to subjects experiencing AEs that cause interruption or discontinuation of ADXS11-001 
or those experiencing AEs that are present at the end of their participation in the study; 
such subjects should receive post treatment follow-up as appropriate.  If an ongoing AE 
changes in its severity or in its perceived relationship to ADXS11-001, a new AE entry in 
the eCRF for the event should be completed. 
13.4 Adverse Events Related to Study Conditions 
If the Investigator believes that an AE is not related to ADXS11-001, but is potentially 
related to the conditions of the study (such as withdrawal of previous therapy or 
complication of a diagnostic procedure), the relationship should be specified in the 
comment section of the AE page of the eCRF and on the Serious Adverse Event Report 
(SAER) form. 
13.5 Overdose 
For purposes of this trial, an overdose will be defined as any ADXS11-001 dose 
exceeding the prescribed dose.  No specific information is available on the treatment of 

 
 
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overdose of ADXS11-001.  In the event of an ADXS11-001 overdose, the subject should 
be observed closely for signs of toxicity.  Appropriate supportive treatment should be 
provided if clinically indicated. 
If an AE(s) is associated with (“results from”) the overdose of an Advaxis product, the 
AE(s) is reported as a SAE, even if no other seriousness criteria are met. 
If a dose of Advaxis’ product meeting the protocol definition of overdose is taken without 
any associated clinical symptoms or abnormal laboratory results, the overdose is reported 
as an AE. 
All reports of overdose with and without an AE must be reported within 24 hours to the 
Sponsor and within 2 working days hours to inVentiv Health Clinical Pharmacovigilance 
(Attn: iHC SAE Reporting; FAX 866-880-9343 or email:  
i3drugsafetyPV@inventivhealth.com). 
13.6 Evaluating Adverse Events 
An Investigator who is a qualified physician will evaluate all AEs according to the 
CTCAE v 4.03 (See Table 12).  Any AE that changes CTCAE grade over the course of a 
given episode will have each change of grade recorded on the AE case report 
forms/worksheets.  All AEs regardless of CTCAE grade must also be evaluated for 
seriousness. 
 

 
 
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Table 12  Evaluating Adverse Events 
V4.03 CTCAE 
Grading 
Grade 1 
Mild; asymptomatic or mid symptoms; clinical or diagnostic observations only; intervention not indicated. 
 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. 
 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation or hospitalization 
indicated; disabling; limiting self-care ADL. 
 
Grade 4 
Life threatening consequences; urgent intervention indicated. 
 
Grade 5 
Death related to AE 
Seriousness 
A serious adverse event is any adverse event occurring at any dose or during any use of Advaxis product that: 
 
†Results in death; or 
 
†Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred (Note: This does 
not include an adverse event that, had it occurred in a more severe form, might have caused death.); or 
 
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or 
 
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even 
if the hospitalization is a precautionary measure for continued observation. (Note: Hospitalization [including hospitalization for an elective 
procedure] for a preexisting condition which has not worsened does not constitute a serious adverse event.); or 
 
†Is a congenital anomaly/birth defect (in offspring of subject taking the product regardless of time to diagnosis);or 
 
Is a new cancer; (that is not a condition of the study) or 
 
Is an overdose (whether accidental or intentional).  Any adverse event associated with an overdose is considered a serious adverse event. An 
overdose that is not associated with an adverse event is considered a non-serious event of clinical interest and must be reported within 24 hours. 
 
Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious 
adverse event when, based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed previously (designated above by a †). 
Duration 
Record the start and stop dates of the adverse event. If less than 1 day, indicate the appropriate length of time and units 
Action taken  
Did the adverse event cause the Advaxis product to be discontinued? 

 
 
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Relationship 
to test drug  
Did the Advaxis product cause the adverse event? The determination of the likelihood that the Advaxis product caused the adverse event will be 
provided by an investigator who is a qualified physician. The investigator’s signed/dated initials on the source document or worksheet that 
supports the causality noted on the AE form, ensures that a medically qualified assessment of causality was done. This initialed document must be 
retained for the required regulatory time frame. The criteria below are intended as reference guidelines to assist the investigator in assessing the 
likelihood of a relationship between the test drug and the adverse event based upon the available information.  
The following components are to be used to assess the relationship between the Advaxis product and the AE; the greater the correlation with the 
components and their respective elements (in number and/or intensity), the more likely the Advaxis product caused the adverse event (AE): 
 
Exposure 
Is there evidence that the subject was actually exposed to the Advaxis product such as: reliable history, acceptable compliance 
assessment (pill count, diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily specimen? 
 
Time Course 
Did the AE follow in a reasonable temporal sequence from administration of the Advaxis product?  
Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational medicinal product)? 
 
Likely Cause 
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or 
environmental factors 
 
Relationship 
The following components are to be used to assess the relationship between the test drug and the AE:  
to Advaxis 
product 
 
Dechallenge 
Was the Advaxis product discontinued or dose/exposure/frequency reduced? 
   If yes, did the AE resolve or improve? 
     If yes, this is a positive dechallenge. If no, this is a negative dechallenge. 
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent disability; (2) the AE resolved/improved 
despite continuation of the Advaxis product; or (3) the trial is a single-dose drug trial); or (4) Advaxis product(s) is/are only used 
one time.) 
 
Rechallenge 
Was the subject re-exposed to the Advaxis product in this study? 
   If yes, did the AE recur or worsen? 
     If yes, this is a positive rechallenge. If no, this is a negative rechallenge. 
(Note: This criterion is not applicable if: (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-
dose drug trial); or (3) Advaxis product(s) is/are used only one time). 
NOTE: IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY 
HAVE BEEN CAUSED BY THE ADVAXIS PRODUCT, OR IF REEXPOSURE TO THE ADVAXIS PRODUCT POSES 
ADDITIONAL POTENTIAL SIGNIFICANT RISK TO THE SUBJECT, THEN THE RECHALLENGE MUST BE 
APPROVED IN ADVANCE BY THE U.S. CLINICAL MONITOR AS PER DOSE MODIFICATION GUIDELINES IN THE 
PROTOCOL. 

 
 
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Consistency 
with Trial 
Treatment 
Profile 
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding the Advaxis product or drug 
class pharmacology or toxicology? 
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical 
judgment, including consideration of the above elements. 
Record one of the following 
Use the following scale of criteria as guidance (not all criteria must be present to be indicative of an Advaxis product 
relationship). 
Definite: 
The event follows a reasonable temporal sequence from administration of the study drug, the event follows a known response 
pattern to the study drug and based on the known pharmacology of the study drug, the event is clearly related to the effect of 
the study drug 
Probable: 
The event follows a reasonable temporal sequence from administration of the study drug and the event follows a known 
response pattern to the study drug AND the event cannot have been reasonably explained by an intercurrent medical condition 
or the event cannot be the effect of a concomitant medication 
Possible 
The event follows a reasonable temporal sequence from administration of the study drug or the event follows a known response 
pattern to the study drug BUT the event could have been produced by an intercurrent medical condition which, based on the 
pathophysiology of the condition, and the pharmacology of the study drug, would be unlikely related to the use of the study drug 
or the event could be the effect of a concomitant medication 
Unlikely 
The event is clearly due to causes distinct from the use of the study drug, such as a documented pre-existing condition, the effect 
of a concomitant medication, a new condition which, based on the pathophysiology of the condition, and the pharmacology of 
the study drug, would be unlikely related to the use of the study drug 
Unrelated 
The event does not follow a temporal relationship to the study treatment administration (too early, late, or study treatment(s) 
not taken) or there is a reasonable causal relationship between another drug, concurrent disease, or circumstance and the AE 

 
 
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13.7 Handling and Reporting of Adverse Events to the Sponsor 
13.7.1 
Serious Adverse Events 
A SAE is any AE occurring at any dose or during any use of Advaxis’ product that: 
 Results in death; 
 Is life threatening; 
 Results in persistent or significant disability/incapacity; 
 Results in or prolongs an existing inpatient hospitalization; 
 Is a congenital anomaly/birth defect; 
 Is a new cancer (that is not a condition of the study); 
 Is associated with an overdose; 
 Is another important medical event 
Progression of the cancer under study is not considered an AE unless it results in 
hospitalization or death. 
Any SAE, or follow up to a SAE, including death due to any cause, that occurs to any 
subject from the time the consent is signed through the completion of the 3-year Lm 
surveillance period whether or not related to Advaxis’ product, must be reported within 
24 hours to the sponsor at inVentiv Health Clinical Pharmacovigilance (Attn: iHC SAE 
Reporting; FAX 866-880-9343 or email: i3drugsafetyPV@inventivhealth.com.   
Additionally, any SAE, considered by an Investigator who is a qualified physician to be 
related to Advaxis’ product that is brought to the attention of the Investigator at any time 
outside of the time period specified in the previous paragraph also must be reported 
immediately to inVentiv Health Clinical Pharmacovigilance (Attn: iHC SAE Reporting; 
FAX 866-880-9343 or email:  i3drugsafetyPV@inventivhealth.com). 
Collection of complete information concerning SAEs is extremely important.  Thus, 
follow-up information that becomes available as the SAE evolves, as well as supporting 
documentation (e.g., hospital discharge summaries and autopsy reports), should be 
collected subsequently, if not available at the time of the initial report, and immediately 
sent using the same procedure as the initial SAE report. 
Periodically, according to Advaxis SOPs, the IB will be updated to include new and 
relevant safety information.  Once the appropriate regulatory authorities have been 

 
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notified of a serious, unexpected, and related event, further reporting of the same event 
will be considered expected. 
SAE reports and any other relevant safety information are to be forwarded to 
inVentiv Health Clinical Pharmacovigilance (Attn: iHC SAE Reporting; FAX 866-
880-9343 or email: i3drugsafetyPV@inventivhealth.com). 
AE reports meeting the requirements of a 7 Day Reports, 15 Day Reports, or the 
requirements for inclusion in the Annual Periodic Reports will be submitted as required 
to FDA, European Union (EU), Pharmaceutical and Medical Devices agency (PMDA) or 
other local regulators.  Investigators will be provided a copy of the submission and will 
utilize this for submission to local IRB/EC as required.  The submission will cross 
reference the Sponsor’s Investigational Compound Number (IND, CSA, etc.). 
All subjects with SAEs must be followed up for outcome. 
13.8 Laboratory Test Abnormalities 
Laboratory tests for hematology, chemistry, urinalysis, and others are specified in Table 
13. 
Laboratory tests should be performed within 3 days prior to dosing.  Subjects must meet 
all lab criteria prior to initial dosing.  For subsequent dosing, hepatic and renal function 
eligibility criteria must be met.  Results must be reviewed by the Investigator or qualified 
designee and found to be acceptable prior to each dose of trial treatment. 
All laboratory test values captured as part of the study should be recorded on the 
appropriate laboratory test results pages of the eCRF.  In addition, in order for Advaxis to 
collect additional information about clinically important laboratory abnormalities, the 
following laboratory abnormalities should be captured on the AE pages of the eCRF: 
 Any laboratory test result that meets the criteria for a SAE; laboratory test results that 
meet the criteria for a SAE should also be reported to Advaxis using the SAER form 
(see Section 13.7, Handling of Serious Adverse Events) 
 Any laboratory abnormality that requires the subject to have ADXS11-001 
discontinued or interrupted 
 Any laboratory abnormality that requires the subject to receive specific corrective 
therapy 
It is expected that wherever possible the clinical, rather than the laboratory term, would 
be used by the reporting Investigator (e.g., anemia versus low hemoglobin value). 

 
 
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Table 13  Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Other 
Hematocrit 
Albumin 
Blood 
Serum β-human chorionic gonadotropin ( (β-hCG) 
Hemoglobin 
Alkaline phosphatase 
Glucose 
PT (INR) 
Platelet count 
Alanine aminotransferase (ALT) 
Protein 
aPTT 
WBC (total and differential) Aspartate aminotransferase (AST) 
Specific gravity  
Blood for correlative studies 
Red blood cell count 
Lactate dehydrogenase (LDH) 
Microscopic exam (If abnormal)  Lm Surveillance blood cultures* 
Absolute neutrophil count 
C-Reactive Protein (CRP)* 
Urine pregnancy test † 
 
 
Carbon dioxide ‡  
 (CO2 or bicarbonate) 
 
 
 
Creatinine 
 
 
 
Calcium 
 
 
 
Chloride 
 
 
 
Erythrocyte Sedimentation Rate (ESR)*  
 
 
Glucose 
 
  
 
Potassium   
 
  
 
Sodium 
 
  
 
Total bilirubin 
 
  
 
Direct bilirubin (If total bilirubin is 
elevated above the upper limit of 
normal) 
 
 
 
Total protein 
 
 
 
Blood urea nitrogen (BUN) 
 
 
† Perform on women of childbearing potential only. If urine pregnancy results cannot be confirmed as negative, a serum pregnancy test will be required. 
‡ If considered standard of care in your region. 
*Lm surveillance Monitoring will include routine monitoring of CBC, CMP (including CRP, ESR) and blood cultures.   

 
 
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13.9 Other Safety Considerations 
Any clinically significant changes noted during interim or final physical examinations, 
X-rays, and any other potential safety assessments, whether or not these procedures are 
required by the protocol, should be recorded on the AE page of the eCRF.  All required 
Lm surveillance labs should be recorded on the lab and AE page of the eCRF, as 
appropriate. 
13.10 Pregnancy 
An Investigator approved method of birth control must be used during the course of the 
study.  Prior to enrollment, study candidates who are women of childbearing potential 
must be advised of the importance of avoiding pregnancy during trial participation and 
the potential risk factors for an unintentional pregnancy.  All women of childbearing 
potential must have a negative pregnancy test within 72 hours prior to receiving 
ADXS11-001.  The minimum sensitivity of the pregnancy test must be 25 IU/L or 
equivalent units of human chorionic gonadotropin.  If the pregnancy test is positive, the 
subject must not receive ADXS11-001 and may not be enrolled in the study. 
Women of childbearing potential is defined as females who have experienced menarche 
and who have not undergone successful surgical sterilization (hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy), are not postmenopausal (defined as 
amenorrhea  12 consecutive months or women on hormone replacement therapy with a 
documented serum follicle stimulating hormone level >35 mIU/ml).  Even women who 
are using oral, implanted, or injectable contraceptive hormones or mechanical products, 
such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides), to 
prevent pregnancy, who are practicing abstinence, and who have a sterile partner 
(e.g., vasectomy) should be considered of childbearing potential. 
All study participants should be instructed to contact the investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual period) at any time during 
study participation. 
In the case of pregnancy, ADXS11-001 will be discontinued and protocol-required 
procedures for study discontinuation and follow-up must be performed on the subject 
unless contraindicated by pregnancy (e.g., X-ray studies).  Other appropriate pregnancy 
follow-up procedures should be considered if indicated. 
Although pregnancy and lactation are not considered AEs, it is the responsibility of the 
investigator or their designees to report any pregnancy or lactation in a subject 
(spontaneously reported to them), that occurs during the trial or 120 days of completing 
the trial, or 30 days following cessation of treatment if the subject initiates new 
anticancer therapy, whichever is earlier.  All subjects who become pregnant must be 
followed to the completion/termination of the pregnancy.  Pregnancy outcomes of 
spontaneous abortion, missed abortion, benign hydatidiform mole, blighted ovum, fetal 
death, intrauterine death, miscarriage and stillbirth must be reported as serious events 

 
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(Important Medical Events).  If the pregnancy continues to term, the outcome (health of 
infant) must also be reported.   
Such events must be reported within 24 hours of awareness to inVentiv Health Clinical 
Pharmacovigilance (Attn: iHC SAE Reporting; FAX 866-880-9343 or email:  
i3drugsafetyPV@inventivhealth.com). 
14 DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
14.1 Introduction 
This is an open-label, single agent clinical trial.  Descriptive statistics will be employed to 
evaluate the safety and tolerance of ADXS11-001.  Summary statistics for continuous 
variables will include mean, standard deviation, median and range.  Categorical variables 
will be presented as frequency counts and percentages; and time-to-event variables will 
be summarized by Kaplan-Meier medians and survival plots.  Data listings will be 
created to support tables and present data.  The preliminary efficacy analysis will be 
conducted on the efficacy evaluable population and safety analysis will be performed on 
the safety population.  SAS 9.2 or higher will be used for data analysis. 
The data will be tabulated and analyzed with respect to subject enrollment and 
disposition, demographic, and baseline characteristics. 
14.2 Statistical Analysis Plan 
This is a Phase 1 open-label, multi-center clinical trial.  Descriptive statistics will be 
employed to evaluate the safety and tolerance of ADXS11-001.  Summary statistics for 
continuous variables will include mean, standard deviation, median and range.  
Categorical variables will be presented as frequency counts and percentages; and time-to-
event variables will be summarized by Kaplan-Meier medians and survival plots.  Data 
listings will be created to support tables and present data.  The safety analysis will be 
performed on the safety population.  The efficacy analysis will be performed on the 
efficacy population.  SAS 9.2 or higher will be used for data analysis. 
The data will be tabulated and analyzed with respect to subject enrollment and 
disposition, demographic, and baseline characteristics. 
14.3 Sample Size 
 The dose escalation portion of the study will enroll between 6-12 subjects based on 
observed AEs and/or DLTs within the dose cohorts. 
 Additional subjects may be enrolled in an expansion cohort of the highest dose level 
to allow approximately 15 subjects to be treated at that dose level. 

 
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14.4 Treatment Randomization and Blinding 
This is an open-label, multi-center trial.  No placebo or active control is used and 
therefore no randomization is involved. 
14.5 Study Populations 
All subjects who receive at least 1 dose of study treatment will be included in the safety 
analyses.  All subjects who complete at least 1 cycle of ADXS11-001 treatment will be 
included in the efficacy population. 
14.5.1 
Subject Disposition 
The number and percentage of subjects entering and completing the clinical study will be 
presented overall and by dose cohort. 
14.5.2 
Demographic Information and Baseline Characteristics 
Demographic and baseline characteristic will be descriptively summarized by study phase 
and dose. 
14.5.3 
Protocol Deviation 
Protocol deviations will be listed by subject. 
14.5.4 
Analysis of Safety 
All subjects who receive at least 1 dose of study treatment will be included in the safety 
analyses. 
All AEs will be summarized by subject, dose, and prior recurrence history (aggressive 
[recurrence within 2 years]/non-aggressive). 
The CTCAE v 4.03 will be used for AE grading (Grades 1 to 4).  AEs will be classified 
using the Medical Dictionary for Regulatory Activities (MedDRA®) coding system. 
The overall incidence of AEs will be summarized and classified by body system and 
ADXS11-001 dose.  An AE will be summarized if the onset date occurs any time during 
study treatment or up to 30 days after the last dose of study treatment; or, if it occurs 
prior to Day 1 and worsens while on therapy.  The type, incidence, severity, and causality 
of each AE, the duration of the event, and any required treatment interventions will be 
tabulated. 
Physical examination results will be presented in the subject data listings.  Vital sign 
measurements will be summarized at each infusion using descriptive statistics.  The 
incidence of clinically significant laboratory abnormalities will be presented, and 
laboratory data will be summarized at each infusion by the CTCAE v 4.03 toxicity 

 
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grades.  Laboratory data will be presented for subjects having Grade 3 or 4 changes from 
baseline. 
14.5.5 
Analysis of Efficacy 
All subjects who complete at least one cycle of ADXS11-001 treatment will be included 
in the efficacy analyses.  The following are efficacy parameters for the study: 
1. Objective Response Rate (ORR) 
2. Duration of tumor response  
3. Stable Disease Rate (proportion of CR, PR, SD) 
4. Duration of Stable Disease (SD) 
5. Progression free survival (PFS) 
Tumor response will be evaluated by RECIST 1.1 and irRECIST criteria.  The ORR will 
be calculated as the proportion of subjects who achieved CR/irCR or PR/irPR.  The 
duration of response is defined as the time interval from CR/irCR or PR/irPR to disease 
progression or death.  If the subject's disease remains responsive by the time of 
discontinuation or completion of the study, the duration will be censored at that time 
point.  The stable disease rate will be calculated as the proportion of subjects who 
achieved CR/irCR, PR/irPR or SD/irSD.  The duration of SD is defined as the time 
interval from CR/irCR or PR/irPR or SD/irSD to disease progression or death.  If the 
subject's disease remains stable by the time of discontinuation or completion of the study, 
the duration will be censored at that time point. 
PFS is defined as the time interval from first infusion of study treatment to disease 
progression or death.  If the subject's disease has not progressed by the time of 
discontinuation or completion of the study, the PFS will be censored at that time point. 
Efficacy parameters will be descriptively summarized by dose cohorts as well as for all 
cohorts combined.  Tumor response will be summarized according to response category.  
Response rate and stable disease rate will be summarized by frequency table.  For 
durations of response and SD/irSD as well as PFS, the Kaplan-Meier method will be used 
to estimate the median times.  Descriptive statistics and Kaplan-Meier curves will be 
presented. 
14.6 Interim Analysis 
No formal interim analysis is planned for the study.  However, AEs and toxicity reports 
will be monitored. 

 
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15 INVESTIGATOR OBLIGATIONS 
15.1 Compliance with the Protocol and Protocol Revision 
International Conference on Harmonisation (ICH) Guidance on Good Clinical Practice 
([GCP] CPMP/ICH/135/95) and Advaxis require the Investigator to be aware of his/her 
obligations in the conduct of this study.  These obligations are listed in the sections 
below. 
When a situation occurs that requires a temporary departure from the protocol, the 
Investigator or other physician in attendance should contact the medical monitor as soon 
as possible in order to discuss the situation and agree on an appropriate course of action.  
The investigator will describe the departure from the protocol and the circumstances 
requiring it on the eCRF. 
The Investigator may not modify this protocol.  Amendments initiated by Advaxis or its 
agents will be confirmed in writing in the form of a protocol amendment.  All such 
amendments must be approved by the IRB/IEC; however, amendments that reduce risks 
to the subjects may be implemented prior to obtaining IRB/IEC approval.  No additional 
subjects can be enrolled until the amendment is approved by the IRB/IEC. 
Documentation of approval signed by the chairperson or designee of the IRB/IEC must 
be sent to Advaxis.  If the revision is an administrative letter, investigators must inform 
and obtain approval from their IRB/IEC. 
15.2 Informed Consent 
The Investigator must ensure that subjects are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical trials in which they 
volunteer to participate. 
15.2.1 
Informed Consent Procedures 
Preparation of the consent form is the responsibility of the investigator and must include 
all elements required by the ICH, GCP, and applicable regulatory requirements and must 
adhere to GCP.  The consent form also must include a statement that Advaxis, its agents, 
and the regulatory authorities have direct access to subject records.  Prior to beginning 
the study, the Investigator must have written IRB/IEC approval of the informed consent 
form and any other information to be provided to the subjects. 
The Investigator must provide the subject or legally acceptable representative with a copy 
of the consent form and written information about the study in the language in which the 
subject is most proficient.  The language must be nontechnical and easily understood.  
The investigator should allow time necessary for the subject or legally acceptable 
representative to inquire about the details of the study.  Informed consent must be signed 
and personally dated by the subject or legally acceptable representative and by the person 

 
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who conducted the informed consent discussion.  The subject or legally acceptable 
representative should receive a copy of the signed informed consent form and any other 
written information provided to study subjects prior to the subject’s participation in the 
trial. 
15.2.2 
Update of Informed Consent 
The informed consent and any other information provided to subjects or legally 
acceptable representative should be revised whenever important new information 
becomes available that is relevant to the subject’s consent and should receive IRB/IEC 
approval prior to use.  The Investigator, or a person designated by the investigator, should 
fully inform the subject or legally acceptable representative of all pertinent aspects of the 
study and of any new information relevant to the subject’s willingness to continue 
participation in the study.  This communication should be documented.  During a 
subject’s participation in the trial, any updates to the consent form and any updates to the 
written information will be provided to the patient. 
If a protocol amendment substantially alters the study design or increases the potential 
risk to the subject:  (1) the consent form must be revised and submitted to the IRB/IEC 
for review and approval, (2) the revised consent form must be used to obtain consent 
from subjects currently enrolled in the study, and (3) the new consent form must be used 
to obtain consent from new subjects prior to enrollment. 
15.3 Monitoring for Protocol Compliance 
Representatives of Advaxis must be allowed to visit all study site locations periodically 
to assess data quality and study integrity.  On site, they will review study records and 
directly compare them with the original source documents, discuss the conduct of the 
study with the investigator, and verify that the facilities remain acceptable. 
In addition, the study may be evaluated by auditors designated by Advaxis and by 
government inspectors who must be allowed access to eCRFs, source documents, and all 
other study files.  Advaxis audit reports will be kept confidential. 
THE INVESTIGATOR MUST NOTIFY ADVAXIS PROMPTLY OF ANY 
INSPECTIONS SCHEDULED BY REGULATORY AUTHORITIES AND 
PROMPTLY FORWARD COPIES OF INSPECTION REPORTS TO ADVAXIS. 
15.4 Records and Reports 
The Investigator will be required to prepare and maintain adequate case histories 
designed to record all observations and other data pertinent to the investigation on each 
individual treated with ADXS11-001 or entered as a control in the investigation.  Data 
reported on the eCRF that are derived from source documents must be consistent with the 
source documents, or the discrepancies must be explained. 

 
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The confidentiality of records and information that could identify subjects must be 
protected, respecting privacy and confidentiality rules in accordance with applicable 
regulatory requirements. 
The Investigator will agree to maintain in confidence all information furnished by 
Advaxis and all data generated in the study, except as provided or required by law, and 
will divulge such information to the IRB/IEC with the understanding that confidentiality 
will be maintained by the committee. 
The identity of all subjects in this study must remain confidential, and only the subjects’ 
initials will appear on the eCRF.  Qualified representatives from the relevant regulatory 
agencies, Advaxis, or its agents may inspect the subject/study records.  Subject data 
obtained during the study may be presented in scientific publications, but at no time will 
subject names be used. 
Subjects will be identified by initials and identification number, if applicable.  All 
requested information must be entered on the eCRF in the spaces provided.  If an item is 
not available or is not applicable, it must be documented as such.  Do not leave a space 
blank. 
The Investigator will maintain a Signature Sheet (Delegation of Authority Page) to 
document signatures and initials of all persons authorized to make entries and/or 
corrections on the eCRFs, as applicable.   
The completed eCRF must be promptly reviewed and electronically signed and dated by 
a qualified physician who is an Investigator or sub-investigator.  If any changes are made 
or additional data are added to an eCRF after the investigator has signed and dated the 
form, the investigator must initial and date the change or addition.  The Investigator must 
retain a copy of the eCRF, including records of changes and corrections. 
All baseline and reassessment radiographs used to assess response must be available for 
independent review. 
15.5 Institutional Review Board/Independent Ethics Committee 
Before study initiation, the investigator must have specified written and dated approval 
from the IRB/IEC for the protocol, consent form, subject recruitment materials/process 
(e.g., advertisements), and any other written information to be provided to subjects.  The 
investigator also should provide the IRB/IEC with a copy of the IB or product labeling, 
information to be provided to subjects, and any updates. 
The Investigator should provide the IRB/IEC with reports, updates, and other information 
(e.g., safety updates, amendments, and administrative letters) according to regulatory 
requirements or institution procedures. 

 
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15.6 Records Retention 
The Investigator must retain ADXS11-001 disposition records, copies of eCRFs (or 
electronic files), and source documents for the maximum period required by applicable 
regulations and guidelines, institution procedures, or the period specified by Advaxis, 
whichever is longer.  The Investigator must contact Advaxis prior to destroying any 
records associated with the study.  Advaxis will notify the investigator when the trial 
records are no longer needed.  If the Investigator withdraws from the study 
(e.g., relocation, retirement), the records shall be transferred to a mutually agreed upon 
designee (e.g., another investigator, IEC).  Notice of such transfer will be given in writing 
to Advaxis. 

 
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