Prospective, Interventional Pilot Study of Mobile Devices and Digital Applications to Detect Early Pneumonitis and Other Pulmonary Adverse Events in Unresectable Stage III Non-Small Cell Lung Cancer Patients on Durvalumab
Phase: PHASE4
Conditions: Unresectable Stage III NSCLC
Sponsor: AstraZeneca

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
1 
 
 
Study Protocol 
Study Code 
D4194C00008 
Version 
V5.0 
Date 
2 December 2020 
Prospective, Interventional Pilot Study of Mobile Devices and Digital 
Applications to Detect Early Pneumonitis and Other Pulmonary Adverse 
Events in Unresectable Stage III Non-Small Cell Lung Cancer Patients on 
Durvalumab 
Effective date: 2 December 2020 
Sponsor: AstraZeneca US, 1800 Concord Pike, Wilmington, DE 19803, USA 
 
 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
12 
 
 
This Clinical Study Protocol has been subject to a peer review according to AstraZeneca 
standard procedures. The Clinical Study Protocol is publicly registered, and the results are 
disclosed and/or published according to the AstraZeneca Global Policy on Bioethics and in 
compliance with prevailing laws and regulations. 
 
 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
13 
 
 
TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................. 1 
VERSION HISTORY ............................................................................................................... 2 
TABLE OF CONTENTS ........................................................................................................ 13 
LIST OF TABLES .................................................................................................................. 15 
LIST OF FIGURES ................................................................................................................. 15 
LIST OF APPENDICES ......................................................................................................... 15 
1 
SYNOPSIS ........................................................................................................... 16 
2 
INTRODUCTION ................................................................................................ 19 
2.1 
Study Rationale ..................................................................................................... 19 
2.2 
Background ........................................................................................................... 19 
2.3 
Benefit/Risk Assessment ...................................................................................... 20 
3 
OBJECTIVES AND ENDPOINTS ...................................................................... 20 
3.1 
Study Objectives ................................................................................................... 20 
3.2 
Study Endpoints .................................................................................................... 21 
4 
METHODOLOGY ............................................................................................... 23 
4.1 
Study Design ......................................................................................................... 23 
4.1.1 
Data Sources ......................................................................................................... 24 
4.2 
Scientific Rationale for Study Design .................................................................. 24 
5 
STUDY POPULATION ....................................................................................... 26 
5.1 
Inclusion Criteria .................................................................................................. 26 
5.2 
Exclusion Criteria ................................................................................................. 26 
5.3 
Discontinuation and Withdrawal of Patients ........................................................ 27 
6 
VARIABLES AND EPIDEMIOLOGICAL MEASUREMENTS ....................... 27 
6.1 
Patient Characteristics .......................................................................................... 27 
6.2 
Exposure and Covariates ...................................................................................... 28 
7 
STUDY CONDUCT ............................................................................................. 29 
7.1.1 
Enrollment ............................................................................................................ 29 
7.1.2 
Study Period ......................................................................................................... 29 
7.1.3 
Technical and Patient Support .............................................................................. 29 
7.1.4 
Patient Compensation ........................................................................................... 30 
7.2 
Data Management ................................................................................................. 30 
7.3 
Data Collection Plan ............................................................................................. 30 
7.4 
Study Procedures .................................................................................................. 32 
7.4.1 
Medical Devices ................................................................................................... 32 
7.4.2 
Symptom Assessments ......................................................................................... 33 
7.4.3 
Quality of Life Assessment Questionnaires ......................................................... 34 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
14 
 
 
7.4.4 
User Experience Questionnaires ........................................................................... 34 
7.4.5 
NSCLC Disease History/Respiratory Disease History ......................................... 34 
7.4.6 
Durvalumab Treatment ......................................................................................... 34 
8 
REGULATORY CONSIDERATIONS ............................................................... 35 
8.1 
Quality Control ..................................................................................................... 35 
8.1.1 
Monitoring ............................................................................................................ 35 
8.1.2 
Training of Study Site Personnel .......................................................................... 35 
8.1.3 
Storage and Retention ........................................................................................... 36 
8.2 
Protection of Human Patients ............................................................................... 36 
8.2.1 
Patient Informed Consent ..................................................................................... 36 
8.2.2 
Confidentiality of Study/Patient Data ................................................................... 37 
8.3 
Management and Reporting of Adverse Events and Device Complaints ............. 37 
8.3.1 
Management and Reporting of Adverse Events ................................................... 37 
8.3.1.1 
Definition of Adverse Event and Serious Adverse Event for Drugs .................... 37 
8.3.1.2 
Definition of Adverse Event and Serious Adverse Event for Medical Devices ... 38 
8.3.1.3 
Adverse Events Information ................................................................................. 39 
8.3.1.4 
Reporting of AEs/SAEs on Durvalumab and Device-Related Events ................. 40 
8.3.1.5 
Reporting of Serious Adverse Events (SAEs) ...................................................... 41 
8.3.2 
Medical Device Deficiencies ................................................................................ 41 
8.3.2.1 
Time Period for Detecting Medical Device Deficiencies ..................................... 42 
8.3.2.2 
Follow-Up of Medical Device Deficiencies ......................................................... 42 
8.3.2.3 
Reporting Patient Complaints about Devices or Mobile Application to Sponsor 42 
8.3.2.4 
Reporting Patient Complaints about Devices or Mobile Application to 
Regulatory Authorities.......................................................................................... 42 
8.4 
Non-Significant Risk Investigational Device Exemption..................................... 43 
9 
STATISTICAL CONSIDERATIONS ................................................................. 44 
9.1 
Sample Size Determination .................................................................................. 44 
9.2 
Populations for Analyses ...................................................................................... 44 
9.3 
Statistical Analyses ............................................................................................... 45 
9.3.1 
Efficacy Analyses ................................................................................................. 45 
9.3.2 
Safety Analyses .................................................................................................... 45 
9.4 
Interim Analyses ................................................................................................... 45 
10 
COMMUNICATION PLAN ................................................................................ 46 
10.1 
Publication Plan .................................................................................................... 46 
10.2 
Compliance with Financial Disclosure Requirements .......................................... 46 
10.3 
Changes to the Protocol ........................................................................................ 46 
11 
REFERENCES ..................................................................................................... 47 
12 
APPENDICES ...................................................................................................... 49 
13 
SIGNATURES ..................................................................................................... 63 

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
16 
 
 
1 SYNOPSIS 
Title of Study: 
Prospective, Interventional Pilot Study of Mobile Devices and Digital Applications 
to Detect Early Pneumonitis and Other Pulmonary Adverse Events in Unresectable 
Stage III Non-Small Cell Lung Cancer Patients on Durvalumab 
Protocol Number: 
D4194C00008 
Background/Rationale: 
The development of new multiparametric healthcare technologies has provided 
new sources of data collection for healthcare providers. This new form of data 
collection may improve healthcare delivery and outcomes. Given the potential 
impact of these new technologies, it is important to understand the utility of 
multiparametric mobile technology for patients and how information collected 
through these can be used to improve patient care. By analyzing disease 
characteristics and health status alongside a specific patient’s history, it may be 
possible to predict changes in organ function and intervene earlier with the 
appropriate medical care. Previous studies have documented the ability of home 
spirometry devices to detect pulmonary adverse events (AEs) in lung transplant 
patients, establishing proof of principle in lung transplant and non-small cell lung 
cancer (NSCLC) populations. 
Multiparametric mobile technology devices and applications are non-invasive and 
simple to use, automatically collecting data from patients and/or allowing patients 
to report data in almost any location, whenever convenient. Multiparametric 
mobile technology has been used in previous studies, where large volumes of data 
were quickly and efficiently entered by a high proportion of patients who 
expressed their satisfaction with the technology. 
Patients undergoing treatment for lung cancer with durvalumab can experience 
pulmonary AEs that lead to treatment discontinuation and morbidity. This study, 
ON TRAX, is a pilot study to evaluate the potential benefit of multiparametric 
mobile applications and connected medical devices in collecting data to facilitate 
or improve early identification of pulmonary AEs in patients with unresectable 
Stage III NSCLC receiving durvalumab treatment. The data collected in this study 
will determine whether this multiparametric mobile technology will be progressed 
to a fully powered study for the early detection of pneumonitis and pulmonary AEs 
in patients with unresectable Stage III NSCLC. This project seeks to understand if 
the multiparametric mobile technology devices integrate well into a patient’s daily 
life with minimal burden and to collect vital signs and respiratory data. These 
devices can then track and detect changes in a patient’s vital signs and respiratory 
function and aid physicians in detection of pulmonary AEs. 

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CCI

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
19 
 
 
2 INTRODUCTION 
2.1 
Study Rationale 
Patients undergoing treatment with durvalumab for unresectable Stage III non-small cell lung 
cancer (NSCLC) after 2 or more cycles of concurrent platinum-based chemotherapy and 
radiation therapy (concurrent chemoradiotherapy [cCRT]) can experience pulmonary adverse 
events (AEs) that lead to treatment discontinuation and morbidity. This study, ON TRAX, is a 
pilot study to evaluate the potential benefit of multiparametric mobile applications and 
connected medical devices in collecting data to facilitate or improve early identification of 
pulmonary AEs in patients with unresectable Stage III NSCLC receiving durvalumab 
treatment. The outcomes of this study will determine whether this multiparametric mobile 
technology will be progressed to a fully powered study for the early detection of pneumonitis 
and pulmonary AEs in patients with unresectable Stage III NSCLC.  
This project seeks to understand if the multiparametric mobile technology devices integrate 
well into a patient’s daily life with minimal burden and to collect vital signs and respiratory 
data. These devices can then track and detect changes in a patient’s vital signs and respiratory 
function and aid physicians in detection of pulmonary AEs. 
2.2 
Background 
The PACIFIC study was a randomized, placebo-controlled, Phase 3 trial evaluating the 
immune checkpoint inhibitor durvalumab in patients with unresectable Stage III NSCLC who 
did not have disease progression after 2 or more concurrent cycles of platinum-based 
chemoradiotherapy. At the first planned interim analysis, the trial showed that durvalumab 
treatment significantly prolonged progression-free survival, as compared with placebo, with 
median durations of 16.8 months (95% confidence interval [CI], 13.0 to 18.1 months) and 
5.6 months (95% CI, 4.6 to 7.8 months), respectively (Antonia et al. 2017). On the basis of 
these results, durvalumab treatment was approved by the United States Food and Drug 
Administration (US FDA) for the treatment of unresectable Stage III NSCLC in patients 
whose disease had not progressed after platinum-based chemoradiotherapy. In addition, 
overall survival was found to be significantly prolonged in durvalumab-treated patients 
compared with the placebo group (stratified hazard ratio for death, 0.68; 99.7% CI, 0.47 to 
0.997; p=0.0025) (Antonia et al. 2018). During the PACIFIC trial, pneumonitis or radiation 
pneumonitis of any grade occurred in 33.9% and 24.8% and Grade 3 or 4 pneumonitis or 
radiation pneumonitis occurred in 3.4% and 2.6% of durvalumab and placebo patients, 
respectively (Antonia et al. 2017). A total of 15.4% of patients in the durvalumab arm 
discontinued study drug due to AEs, compared with 9.8% in the placebo arm (Antonia et al. 
2018). The most frequent AEs leading to study drug discontinuation were pneumonitis (4.8% 
in the durvalumab group and 2.6% in the placebo group), radiation pneumonitis (1.3% in both 
groups), and pneumonia (1.1% in the durvalumab group and 1.3% in the placebo group). 
Immune checkpoint-inhibitor-related pneumonitis is a potentially serious and life-threatening 
toxicity. The reported incidence of pneumonitis in studies investigating anti-programmed cell 
death 1/programmed cell death-ligand 1 is variable and ranges from 0% to 10%, with an 
overall incidence of 2.7% reported in a recent meta-analysis of 20 studies with programmed 
cell death 1 (PD-1) inhibition; the incidence in patients with lung cancer as the underlying 
diagnosis is even higher (Nishino et al. 2016). 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
20 
 
 
The development of new multiparametric healthcare technologies has provided new sources of 
data collection for healthcare providers. This new form of data collection may improve 
healthcare delivery and outcomes. Given the potential impact of these new technologies, it is 
important to understand the utility of multiparametric mobile technology for patients and how 
information collected through these can be used to improve patient care. By analyzing disease 
characteristics and health status alongside a specific patient’s history, it may be possible to 
predict changes in organ function and intervene earlier with the appropriate medical care. 
Previous studies have documented the ability of home spirometry devices to detect pulmonary 
AEs in lung transplant patients, establishing proof of principle in lung transplant and NSCLC 
populations (Finkelstein et al. 1999; Finkelstein et al. 2013; Wang et al. 2013; 
Torre-Bouscoulet et al. 2018; Basch et al. 2017). 
Multiparametric mobile technology devices and applications are non-invasive and simple to 
use, automatically collecting data from patients and/or allowing patients to report data in 
almost any location, whenever convenient. Multiparametric mobile technology has been used 
in previous studies (QUASAR 2; Cloudy with a Chance of Pain Study), where large volumes 
of data were quickly and efficiently entered by a high proportion of patients who expressed 
their satisfaction with the technology. 
2.3 
Benefit/Risk Assessment 
All patients who participate in this study will receive standard of care appropriate for their 
lung cancer as determined by their treating physician. 
The technology to be used in this study is non-invasive and has been used previously in other 
settings, including clinical studies; it is believed to pose an extremely low risk to study 
patients. Patients using the wearable arm device have reported minor events of skin irritation 
and discomfort during sleeping. In addition, patients undergoing concomitant anti-coagulation 
therapy have experienced ecchymosis near the device site. As part of their standard of care, 
patients will undergo routine assessment by their physician, who will decide when regular 
visits should take place. Due to the nature of the technology used and the fact that all other 
procedures are standard of care, study-related or multiparametric mobile technology-related 
AEs are expected to be rare. The study sponsor, AstraZeneca (AZ), has concluded that this 
study has a favorable benefit/risk ratio. 
Data from this pilot study will be used by AZ to decide whether a larger comparative study of 
patients with and without the technology is warranted, which will potentially benefit other 
patients in the future. 
3 OBJECTIVES AND ENDPOINTS 
3.1 Study Objectives 
The primary objective of the study is to describe the identification of treatment-emergent 
pneumonitis by grade (regardless of radiation therapy and/or immune-related etiology) in 
patients with unresectable Stage III NSCLC receiving durvalumab through the use of mobile 
technology which collects patient reported outcomes (PROs), vital signs (temperature, heart 
rate, respiratory rate), oxygen saturation (pulse oximetry), pulmonary function tests 
(spirometry), and physical movement (number of steps per day). 

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
23 
 
 
4 
METHODOLOGY 
4.1 
Study Design 
This is a multicenter, prospective, interventional pilot study conducted in the United States 
that will include patients with unresectable Stage III NSCLC whose disease has not 
progressed following 2 or more cycles of cCRT, and who will be treated with durvalumab for 
up to 12 months or until confirmed disease progression, permanent discontinuation of 
durvalumab, the initiation of alternative cancer therapy, unacceptable toxic events, death, or 
withdrawal of consent, whichever is sooner. 
Patients will be enrolled after their treating physician has prescribed durvalumab and before 
they start durvalumab treatment. Patients will receive mobile and wearable devices alongside 
their durvalumab treatment without any additional interventions. Patients will receive training 
on the mobile applications and supportive devices. Patients will return to their study site for 
routine visits and durvalumab infusions as guided by their physician over the duration of the 
study. 
All patients will receive routine medical care as determined by their physician and will be 
instructed to contact the site with any new or worsening symptoms including, but not limited 
to: trouble breathing, chest pain, new or worsening cough, productive cough with purulent 
secretions, shortness of breath, fever, or tachycardia. 
An overview of the study design is presented in Figure 1. 
Figure 1 
Study Design 
 

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CCI

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
25 
 
 
decision making to move to a larger trial. Additional details will be found in the statistical 
analysis plan (SAP). 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
26 
 
 
5 STUDY POPULATION 
The population will be comprised of 75 patients with unresectable Stage III NSCLC whose 
disease has not progressed following 2 or more cycles of cCRT, and who are eligible to 
receive durvalumab, as outlined in the package insert. Patients will be recruited in up to 30 
sites. 
Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this 
study. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, are not permitted. 
5.1 
Inclusion Criteria 
Patients are eligible to be included in the study only if all of the following inclusion criteria 
apply: 
1. Patient able to provide written signed informed consent prior to any study-specific 
procedures. 
2. Patient must be  18 years except in the state of Alabama where the legal age is 
19 years. 
3. Patient has unresectable Stage III NSCLC that has not progressed following concurrent 
platinum-based chemotherapy and radiation therapy and is eligible to receive 
durvalumab according to the US FDA approved package insert. 
4. Patient will initiate durvalumab treatment within 2 weeks of Baseline and receive at 
least 1 dose of durvalumab. 
5. Patient is able and willing to use the mobile application and connected devices on a 
daily basis for up to 12 months. 
6. Patient is able to complete QoL assessments once every 2 weeks for the first 3 months 
of the study and monthly thereafter. 
5.2 
Exclusion Criteria 
Patients meeting any of the following criteria will be excluded from the study: 
1. Patient is currently enrolled in an interventional research study or clinical trial. 
2. Patient is currently oxygen dependent. 
4. Patient has comorbidities that will prevent consistent and reliable measurement 
assessments with multiparametric mobile technology including severe chronic 
obstructive pulmonary disorder (COPD) (defined as patients who, according to the 
Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2019 guidelines, 
have severe and very severe airflow limitation due to COPD; these are patients with 
forced expiratory volume/forced vital capacity [FEV1/FVC] < 0.70 and FEV1 < 50% 
predicted), severe asthma, congestive heart failure [CHF], interstitial lung disease 
[ILD], and others). 
5. Patients on other immunotherapy or systemic immunosuppressants other than 
durvalumab. 
6. Patients with active or prior autoimmune disease or history of immunodeficiency, 
any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) 

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CCI

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
28 
 
 
o Respiratory rate 
o Oxygen saturation (pulse oximetry) 
o Pulmonary function tests including: FEV1, FVC, FEV1/FVC ratio: obstructive 
versus restrictive, and peak expiratory flow (PEF) 
 Comfort and familiarity with technology, including, but not limited to, internet use, 
ownership of smartphones, email use, etc. 
 Relevant concomitant medications including, but not limited to, respiratory 
medications 
 Abbreviated medical history (from birth to Baseline visit) 
 Relevant previous respiratory medical history or procedures including, but not limited 
to, thoracentesis, subsequent radiation, etc. 
 Disease characteristics, such as date of diagnosis, stage at diagnosis, current stage, etc. 
 Previous treatments for NSCLC, including sequential CRT, cCRT regimen for 
unresectable Stage III NSCLC 
 Time since most recent radiation 
6.2 
Exposure and Covariates 
The primary exposure for this study will be multiparametric mobile technology in patients 
with unresectable Stage III NSCLC receiving durvalumab. As part of the inclusion criteria, 
patients may initiate durvalumab treatment within 2 weeks of Baseline. The decision to 
prescribe durvalumab will be made before enrollment, based on physician recommendation. 
The site physician or qualified site personnel will discuss the study with the patient after 
agreement to initiate durvalumab treatment, and the patient will be enrolled after consent and 
evaluation of eligibility using inclusion/exclusion criteria. 

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CCI

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
30 
 
 
asked to contact the study site for issues related to study procedures or for technical support. 
The study site will facilitate connection with the Current Health Call Center for assistance, as 
necessary. For medical questions or to report AE signs/symptoms, patients will be asked to 
contact their treating physicians directly. 
7.1.4 
Patient Compensation 
To recognize the significant time commitment the patients will make in completing daily 
tasks, patients will be compensated for their participation in the study. Patients who enroll in 
the study will be compensated for successfully completing the Day 1 Baseline visit and for 
each successful week on the study.  
7.2 
Data Management 
For this study Cisiv’s Baseline Plus database platform will be used (Cisiv Baseline Plus).  
Baseline Plus will be used to capture data from a patient’s medical records. The Current 
Wearable Health Monitoring System will capture the symptomatic and specific device data 
from the patients. This data will be combined with the data in the Baseline Plus database at the 
end of the study. 
High quality data standards will be maintained, and processes and procedures will be used to 
ensure that the data are as clean and accurate as possible when presented for analysis. Data 
quality will be enhanced through a series of programmed data quality checks that 
automatically detect missing or anomalous data. All the modifications to the data will be 
recorded in an audit trail. 
7.3 
Data Collection Plan 
The data collection plan presented in Table 1 outlines all data points that will be obtained 
from patients’ medical records, mobile devices, and QoL questionnaires, as collected in the 
tablet application, in the study. All patients in the study will attend routine visits, as 
recommended by the treating physician.

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
33 
 
 
The Current Wearable Health Monitoring System is intended for: 
 Continuous monitoring of the following parameters in adults: 
o Pulse rate (Multiparametric wearable device) 
o Oxygen saturation (Multiparametric wearable device) 
o Skin temperature (Multiparametric wearable device) 
o Movement (Multiparametric wearable device) 
 Intermittent monitoring in adults of: 
o Respiration rate (Multiparametric wearable device)  
o Lung function & spirometry (Spirobank G Spirometer) 
o Non-invasive blood pressure (feature not used in this study) 
o Weight (feature not used in this study) 
Training for the patients on the above devices and application will be provided by the 
investigative site personnel. Qualified site personnel as identified by the PI will review data 
collected by the devices once daily during business hours (exempting office closures, such as 
holidays, weekends, etc.), and will contact patients if a clinical intervention is necessary or if 
there are other issues related to study procedures. However, patients will be advised to contact 
their treating physicians directly if they are experiencing new or worsening of existing AE-
related-symptoms. Technical support will be provided by the study site and Current Health 
Call Center as described in Section 7.1.3. 
7.4.2 
Symptom Assessments 
Pulmonary function data collected via mobile applications and devices are described in Table 
3.  
Table 3 
Data Collected via the Current Wearable Health Monitoring System 
 
Pulmonary Function Parameters  
Lowest Acceptable 
Value*  
FEV1  
LLN 
FVC 
LLN 
FEV1/FVC ratio 
LLN 
Oxygen saturation 
90% 
PEF 
LLN 
FEV1 = forced expiratory volume; FVC = forced vital capacity; LLN = lower 
limit of normal; PEF = peak expiratory flow 
* Measurements less than the LLN indicate the presence of an abnormality 
Study physicians should review values lower than normal on a daily basis in alignment with 
regular business hours (as noted above) and patients will be contacted if clinical intervention 
is necessary. 

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CCI

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
35 
 
 
8 
REGULATORY CONSIDERATIONS 
8.1 
Quality Control 
8.1.1 
Monitoring 
AstraZeneca has delegated study monitoring to Syneos Health. Before the first patient is 
enrolled into the study, a Syneos Health designee will meet with the physicians (and other site 
personnel involved with the study) to discuss the joint responsibilities with regards to protocol 
compliance. The roles and responsibilities of Syneos Health and AZ or its representatives will 
be covered. This will be documented in a study Primary Agreement between the designated 
parties and the Primary Investigators (site physician) for each site. 
During the study, a Syneos Health designee or AZ can implement various activities to assure 
compliance with AZ standards of quality. These activities could include but are not limited to: 
Contacts with the sites to: 
 Provide information and support to the physicians and other site personnel 
 Ensure recruitment is meeting expectations for all sites 
 Ensure that site personnel follow the appropriate process to ensure the patient ICFs are 
signed and stored at the site 
 Ensure that site personnel follow the appropriate process to ensure patient’s ON 
TRAX study participant identifiers are captured in the ICFs, as well as the contact 
details as required for the study 
Monitoring activities (remotely, and before on site visit, if required) for: 
 Checking a sample of ICFs at each site 
 Checking a sample of patient data entry at each site 
If there are any issues noted with ICFs or patient data entry that reflect a potential non-optimal 
level of protocol compliance by the site personnel, specific measures will be adopted by 
Syneos Health or AZ to evaluate the situation, identify the issue, and implement specific 
action plans to correct the situation. 
8.1.2 
Training of Study Site Personnel 
The site physician will ensure that appropriate training relevant to the study is given to site 
personnel, and that any new information relevant to the performance of this study is forwarded 
to the staff involved. 
Representatives of the AZ’s quality assurance unit/monitoring team, AZ’s delegate, and 
competent regulatory authorities must be permitted to inspect all study-related documents and 
other materials at the site that support study data entry, including the Investigator Site File, the 
completed ICFs and the patients’ medical records. Audits may be conducted at any time 
during or after the study to ensure the validity and integrity of the study data. 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
36 
 
 
8.1.3 
Storage and Retention 
Following closure of the study, the site physician has the responsibility to ensure maintenance 
of all site study records (except for those required by local regulations to be maintained 
elsewhere), in a safe and secure location. 
The records must be maintained to allow easy and timely retrieval, when needed (e.g., for 
AZ’s or its representative’s audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site personnel. 
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g., microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken. 
The site physician must ensure that all reproductions are legible and are a true and accurate 
copy of the original and meet accessibility and retrieval standards, including regenerating a 
hard copy, if required. Furthermore, the site physician must ensure there is an acceptable 
backup of these reproductions and that an acceptable quality control process exists for making 
these reproductions. 
AstraZeneca or its representatives will inform the site physician of the period for retaining 
these records to comply with all applicable regulatory requirements. The minimum retention 
time will meet the strictest standard applicable to that site for the study with a minimum of 
5 years, as dictated by any institutional requirements or local laws or regulations, AZ/delegate 
standards/procedures, and/or institutional requirements. 
8.2 
Protection of Human Patients 
This study will be performed in accordance with ethical principles that are consistent with the 
Declaration of Helsinki, Good Pharmacoepidemiology Practices (GPP), and applicable 
legislation for prospective studies. 
The site physicians will perform data collection for the study in accordance with the 
regulations and guidelines governing medical practice and ethics in the United States. 
The final protocol of the study, including the final version of the ICF, and submission of an 
Investigational Device Exemption must be approved or given a favorable opinion in writing 
by the appropriate Institutional Review Board (IRB) for each site. 
The IRB must also approve amendments to the protocol and all advertising used to recruit 
patients for the study, according to local regulations. 
8.2.1 
Patient Informed Consent 
The physician at each site will ensure that the patient is given full and adequate oral and 
written information about the nature, purpose, possible risk, and benefit of the study via the 
Informed Consent Process. Patients must also be notified that their participation is voluntary 
and they are free to discontinue from the study at any time. The patients should be given the 
opportunity to ask questions and allowed time to consider the information provided. The 
patients will be required to sign a statement of informed consent that meets the requirements 
of US FDA Code of Federal Regulations (CFR) 21CFR 50, local regulations, Health 

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
38 
 
 
electrocardiogram). In clinical studies, an AE can include an undesirable medical condition 
occurring at any time after the Baseline visit (Day 1) once the patient signs the ICF, even if no 
study treatment has been administered. A treatment-emergent AE (TEAE) is an AE that starts 
or worsens at any time after initiation of a pharmaceutical product on the first day of treatment 
through the End-of-Study visit. 
An SAE is an AE occurring during any study phase after the patient signs the ICF (i.e., at 
Baseline, treatment, washout, follow-up) that fulfills 1 or more of the following criteria: 
 Results in death 
 Is immediately life-threatening 
 Requires in-patient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions 
 Is a congenital abnormality or birth defect 
 Is an important medical event that may jeopardize the patient or may require medical 
intervention to prevent 1 of the outcomes listed above 
Adverse Events (AEs) for malignant tumors reported during a study should generally be 
assessed as SAEs. If no other seriousness criteria apply, the “Important Medical Event” 
criterion should be used. In certain situations, however, medical judgement on an individual 
event basis should be applied to clarify that the malignant tumor event should be assessed and 
reported as a non-serious AE. For example, if the tumor is included as medical history and 
progression occurs during the study, the AE may not fulfil the attributes for being assessed as 
serious, although reporting of the progression of the malignant tumor as an AE is valid and 
should occur.  
Life-threatening in this context refers to a reaction in which the patient was at risk of death at 
the time of the reaction; it does not refer to a reaction that hypothetically might have caused 
death if more severe. 
Medical and scientific judgement should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life-threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
8.3.1.2 Definition of Adverse Event and Serious Adverse Event for Medical 
Devices 
An AE is any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in patients, users, or other persons 
whether or not considered related to the medical device. This includes events considered 
related to the medical device and events considered related to the study procedures involved. 
An SAE is an AE occurring during any study phase after the patient signs the ICF that fulfils 1 
or more of the following criteria: 
 Led to death 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
39 
 
 
 Led to a serious deterioration in health of the patient, that either: 
o Resulted in a life-threatening illness or injury, or 
o Resulted in a permanent impairment of a body structure or a body function, or 
o Required in-patient hospitalization or prolongation of existing hospitalization, 
or 
o Resulted in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, or 
o Led to fetal distress or a congenital abnormality or birth defect 
Serious Injury is an injury or illness that: 
 Is life-threatening 
 Results in permanent impairment of a body function or permanent damage to a body 
structure 
 Necessitates medical or surgical intervention to preclude permanent impairment of a 
body function or permanent damage to a body structure 
 “Permanent” means irreversible impairment or damage to a body structure or function, 
excluding trivial impairment or damage 
 A life-threatening injury meets the definition of serious injury, regardless of whether 
the threat was “temporary” 
It should also be noted that a device does not have to malfunction for it to cause or contribute 
to a serious injury. Even though a device may function properly, it can still cause or contribute 
to a death or serious injury. 
Medical Device Reporting (MDR) Reportable Event (“Reportable Event”): According to the 
US FDA 21CFR 803.3, a Reportable Event means: 
(1) An event that user facilities become aware of that reasonably suggests that a device 
has or may have caused or contributed to a death or serious injury, or 
(2) An event that manufacturers or importers become aware of that reasonably suggests 
that one of their marketed devices: 
i.  May have caused or contributed to a death or serious injury, or 
ii. Has malfunctioned and that the device or a similar device marketed by the 
manufacturer or importer would be likely to cause or contribute to a death or 
serious injury if the malfunction were to recur. 
8.3.1.3 Adverse Events Information 
AE and SAE collection will occur at Baseline (i.e., after the patient signs the ICF), during 
standard of care visits, at the End-of-Study visit, and for 30 days after the End-of-Study visit. 
The following information should be collected for AEs and SAEs reported to AZ or its 
delegate, Syneos Health Pharmacovigilance: 
 AE (verbatim) 
 The date (and time) when the AE started and stopped 
 Intensity rating scale (intensity, maximum intensity or changes in intensity) 
o Mild 
o Moderate 

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
42 
 
 
Definition of Device Deficiency 
A device deficiency is any malfunction or deterioration in the characteristics and/or 
performance of a device as well as any inadequacy in the labelling or the instructions for use 
which, directly or indirectly, might lead to or might have led to the death of a 
participant/user/other person or to a serious deterioration in his/her state of health 
NOTE: Incidents fulfilling the definition of an AE/SAE will also follow the processes outlined 
in Section 8.3.1. 
8.3.2.1 Time Period for Detecting Medical Device Deficiencies 
Medical device incidents or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used. 
If the Investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the Investigator will promptly notify AZ or its designee. 
8.3.2.2 Follow-Up of Medical Device Deficiencies 
Follow-up applies to all participants, including those who discontinue study intervention. The 
Investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. New or 
updated information will be recorded on the originally completed form with all changes 
signed and dated by the Investigator. 
8.3.2.3 Reporting Patient Complaints about Devices or Mobile Application to Sponsor 
Patients will be asked to contact the study site with any technical complaints about their 
devices or applications (e.g., device is not working or pairing, application is not working 
properly). Detailed information about reporting complaints with devices or the mobile 
application will be included in the Patient Study Guide. The study site will facilitate 
connection with the Current Health Call Center for assistance, as necessary. If the Current 
Health Call Center cannot fix the technical complaint within 24 hours, the Current Health Call 
Center will send the patient a replacement device along with a prepaid return shipping label 
for patients to send the faulty device back to Current Health.  
Device deficiencies will be reported to AZ or its designee within 24 hours after the 
investigator determines that the event meets the protocol definition of a medical device 
deficiency. A Medical Device Deficiency Report Form will be sent to AZ or its designee and 
reported to the appropriate device manufacturer as necessary. Any AEs/SAEs that occur as a 
result of the device complaint are to be sent to the AZ DES. Device malfunctions that do not 
result in an AE will be tracked separately. 
8.3.2.4 Reporting Patient Complaints about Devices or Mobile Application to 
Regulatory Authorities 
The Investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for AZ to fulfil the legal responsibility to notify 
appropriate regulatory authorities and other entities about certain safety information relating to 
medical devices being used in clinical studies. Reported complaints will be closely monitored 
and evaluated in context of study continuation. The Investigator, or responsible person 

Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
43 
 
 
according to local requirements (eg, the head of the medical institution), will comply with the 
applicable local regulatory requirements relating to the reporting of device deficiencies to the 
IRB. 
8.4 
Non-Significant Risk Investigational Device Exemption 
This study is not being conducted as a Non-Significant Risk Investigational Device as the 
device is not an investigational device. Previous versions of this device have obtained 510(k) 
clearance by FDA. While the version used in this study has been modified, it would not 
require submission to FDA because the modifications and product codes (Table 2) are within 
the scope of FDA’s June 2020 (further revised in October 2020) guidance, “Enforcement 
Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring 
During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency (Revised)”.

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Final Study Protocol – v5.0; 2 December 2020 
AstraZeneca 
CONFIDENTIAL AND PROPRIETARY 
45 
 
 
Table 5  
Analysis Populations 
 
Population 
Description 
Full Analysis Set (FAS) 
All enrolled patients who take at least 1 dose of durvalumab and who have 
any post-baseline assessment (safety or otherwise). 
Safety Analysis Set (SAF) 
All enrolled patients who take at least 1 dose of durvalumab 
9.3 
Statistical Analyses 
A comprehensive SAP will be developed and finalized before database lock and will describe 
the patient populations to be included in the analyses, as well as the procedures for accounting 
for missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints. All analyses of the primary, secondary, and 
exploratory endpoints will be descriptive only with no formal statistical testing. Any 
deviations from this plan will be reported in the clinical study report. 
9.3.1 
Efficacy Analyses 
PRO values and values from the mobile technology will be considered in connection with 
events of interest, specifically pneumonitis. Contributions to the identification/prediction of 
pneumonitis from PROs and variables collected by the devices may be assessed using 
regression models (e.g. logistic regression) depending on the number of events of interest that 
are observed in the study; the primary endpoint in these estimations will be the occurrence of 
pneumonitis. Lagged PRO values and values collected from the mobile technology may be 
incorporated as covariates in these models; more details will be specified in the SAP. The 
analyses of the primary endpoint will be conducted by overall patients in the full analysis set 
(FAS). 
Continuous secondary and exploratory endpoints (e.g., duration of durvalumab treatment, 
duration of pulmonary AE, and absolute QoL and its change from baseline) will be 
summarized by the number of observations, mean, standard deviation, median, minimum, 
maximum, and 95% CIs. Categorical variables will be summarized by frequency counts, 
percentages, and 95% CIs for each category. All descriptive statistics of secondary and 
exploratory endpoints will be conducted by overall patients in the FAS. 
9.3.2 
Safety Analyses 
Safety analyses will include all patients in the safety analysis set (SAF). 
Safety analyses will involve examination of the descriptive statistics and individual patient 
listings for clinical tolerability and safety. 
Summaries of TEAEs will include the events by system organ class and preferred term, events 
by maximum intensity, event by relationship to study treatment, events leading to study 
discontinuation, and SAEs. 
9.4 
Interim Analyses 
An interim analysis is not planned for the study. 

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10 
COMMUNICATION PLAN 
10.1 
Publication Plan 
In alignment with AZ policies, a study report will be prepared by AZ’s delegate, Syneos 
Health, within 12 months after completion of the study. Reports will be prepared for each of 
the major analysis steps specified in the protocol. The final report will encompass all planned 
analyses, including a description of the complete study population, as described above and in 
the corresponding data analysis plan. 
The final results of the study will be disseminated through submission of manuscripts for 
publication and guided by the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals: Writing and Editing for Biomedical Publication of the International 
Committee of Medical Journal Editors (ICMJE). Selected final results may also be 
disseminated through publication or presentation at scientific meetings. 
All publications shall be developed in accordance with AZ Global Publications Policy, as well 
as ICMJE and Good Publications Practice 3 (GPP3) requirements for authorship and good 
publications practice. Publication decisions, including what, when, and where to publish, will 
be made jointly by AZ authors and study site authors. 
Aggregate results will be published ahead of site-specific or subgroup analyses. AstraZeneca 
reserves the right to delay site-specific or subgroup analyses publications until overall 
aggregate results are published. 
10.2 
Compliance with Financial Disclosure Requirements 
Financial compensation will be provided to cover all study procedures under the responsibility 
of the site physician. This compensation rate will be determined according to recommended 
fair market value for the corresponding study activities. 
Financial disclosure of this compensation will fulfil applicable local laws, codes, and 
regulations. 
10.3 
Changes to the Protocol 
Changes to the protocol will be documented in written protocol amendments. Major (ie, 
substantial, significant) amendments will be approved by the relevant regulatory authorities 
and will usually require submission or notification to the relevant IRB for approval or 
favorable opinion, if applicable. In such cases, the amendment will be implemented at the site 
only after approval or favorable opinion has been obtained. 
Minor (non-substantial) protocol amendments, including administrative changes, will be filed 
at each participating site and will be submitted to the relevant IRB or regulatory authorities 
where required by pertinent regulations. Any amendment that could have an impact on the 
patient’s agreement to participate in the study requires the patient’s informed consent prior to 
continued participation in the study. 
Amendments and updates to the protocol will be documented in a separate protocol section 
entitled “Version History”. 

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11 
REFERENCES 
Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III 
Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919-1929. 
Antonia SJ, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after 
Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350. 
Basch E, Deal AM, Dueck AC, et al. Overall Survival Results of a Trial Assessing Patient-
Reported Outcomes for Symptom Monitoring During Routine Cancer 
Treatment. JAMA. 2017;318(2):197-198. 
Cisiv Baseline Plus: Next generation web-based software platform. From URL: 
https://www.cisiv.com. [Accessed 9th January 2019]. 
Cloudy with a Chance of Pain Study. From URL: https://www.cloudywithachanceofpain.com 
[Accessed 8th January 2019]. 
Finkelstein SM, Snyder M, Stibbe EC, et al. Staging of Bronchiolitis Obliterans Syndrome 
Using Home Spirometry. Chest. 1999;116(1):120-126. 
Finkelstein SM, Lindgren BR, Robiner W, et al. A Randomized Controlled Trial Comparing 
Health and Quality of Life of Lung Transplant Recipients Following Nurse and Computer-
Based Triage Utilizing Home Spirometry Monitoring. Telemed J E Health. 2013;19(12):897-
903. 
Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative 
for Chronic Obstructive Lung Disease (GOLD) 2019. From URL: https://goldcopd.org. 
[Accessed 22nd May 2019]. 
International Committee of Medical Journal Editors (ICMJE). Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals. From URL: https://www.ICMJE.org. 
[Accessed 15th January 2019]. 
Nishino M, Giobbie-Hurder A, Hatabu H, et al. Incidence of Programmed Cell Death 1 
Inhibitor Related Pneumonitis in Subjects With Advanced Cancer: A Systematic Review and 
Meta Analysis. JAMA Oncol. 2016;2(12):1607-1616. 
Quick and Simple and Reliable (QUASAR) 2 Study. Weaver A, Young AM, Rowntree J, et 
al. Application of mobile phone technology for managing chemotherapy-associated side 
effects. Annals of Oncology. 2007;18(11):1887-1892. 

Final Study Protocol – v5.0; 2 December 2020 
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CONFIDENTIAL AND PROPRIETARY 
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Torre-Bouscoulet L, Muñoz-Montaño WR, Martínez-Briseño D, et al. Abnormal pulmonary 
function tests predict the development of radiation-induced pneumonitis in advanced non-
small cell lung Cancer. Respir Res. 2018;19(1):72. 
United States Food and Drug Administration (US FDA). Guidance for Industry and Food and 
Drug Administration Staff. Enforcement Policy for Non-Invasive Remote Monitoring Devices 
Used to Support Patient Monitoring During the Coronavirus Disease 2019 (COVID-19) Public 
Health Emergency (Revised). October 2020. Available from: https://www. 
https://www.fda.gov/media/136290/download. 
Wang W, Finkelstein SM, Hertz MI. Automatic Event Detection in Lung Transplant 
Recipients Based on Home Monitoring of Spirometry and Symptoms. Telemed J E Health. 
2013;19(9):658-663.