A Multicenter Study of the NEUWAVE Flex Microwave Ablation System in the Ablation of Medically Inoperable Primary Soft Tissue Lesions of the Lung: An Initial Experience
Phase: NA
Conditions: Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Carcinoma, Non-Small Cell Lung, Non-Small Cell Lung Cancer, Non-Small-Cell Lung Carcinoma
Sponsor: Ethicon, Inc.

 
 
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A Multicenter Study of the NEUWAVE Flex Microwave 
Ablation System in the Ablation of Medically Inoperable 
Primary Soft Tissue Lesions of the Lung:  
An Initial Experience  
 
Sponsor Protocol Number: NEU_2017_06 
 
 
Document 
Effective Date 
Original (version 1.0) 
25 Jan 2018 
Amendment 1 (version 2.0) 
08 Jun 2018 
Amendment 2 (version 3.0) 
25 Jul 2018 
 
Sponsor: 
 
 
 
NeuWave Medical, Inc. 
3529 Anderson Street Madison WI 53704 
 
Sponsor’s Medical Directors: 
Edmund Kassis, MD / Joe Amaral, MD 
 
 
 
 
 
NeuWave Medical, Inc. 
713-444-7907 / 513-337-7722 
 
Name of Finished Product: 
NEUWAVE Flex Microwave Ablation System  
and Accessories 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged 
or confidential and may not be disclosed unless such disclosure is required by applicable law or 
regulations. In any event, persons to whom the information is disclosed must be informed that the 
information is privileged or confidential and may not be further disclosed by them. These restrictions on 
disclosure will apply equally to all future information supplied to you which is indicated as privileged or 
confidential. 

 
 
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Sponsor Signature  
 
 
Protocol Number:   
NEU_2017_06 
Protocol Title:   
A Multicenter Study of the NEUWAVE Flex Microwave 
Ablation System in the Ablation of Medically 
Inoperable Primary Soft Tissue Lesions of the Lung: 
An Initial Experience 
Protocol Amendment 2 Date: 
25 Jul 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
 
 
Leonie Rynn, M.D. 
Vice President, Clinical Research 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This study will be performed in compliance with Good Clinical Practice (and in accordance 
with the Declaration of Helsinki), as well as all applicable local regulations. 
 

 
 
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INVESTIGATOR SIGNATURE 
 
I have read this protocol and agree to conduct this clinical investigation in accordance with the 
design and specific provisions outlined herein. I understand the protocol, and I understand I 
am solely responsible to ensure the investigation is conducted in accordance with Good 
Clinical Practices (GCP), applicable country regulations, the Declaration of Helsinki, the 
signed clinical study contract with Sponsor, and with the protocol outlined herein. I will conduct 
this study as outlined therein and will make reasonable effort to complete the study within the 
time period designated by the Sponsor.   
I will provide copies of the protocol and all pertinent information to all individuals responsible 
to me who will assist in the conduct of this study. I will discuss this material with them to ensure 
they are fully informed regarding the device and the conduct of the study.  
I will fulfill the requirements of my Institutional Review Board (IRB)/Ethics Committee (EC), or 
other oversight committee, to ensure complete and continual oversight of this clinical 
investigation. I will use an Informed Consent Document approved by the Sponsor and my 
reviewing IRB/EC (where required).  
I agree to report all information or data in accordance with the protocol and, in particular, I 
agree to report any serious adverse events, device related adverse events, or procedure 
related adverse events as defined in this protocol to the Sponsor, and comply with all adverse 
event reporting requirements of my reviewing IRB/EC. I agree to permit the Sponsor, its 
authorized representatives, my reviewing IRB/EC, and any regulatory authority/body access 
to all records relating to the clinical investigation. 
The below signature confirms I have read and understood this protocol and its associated 
amendments or attachments, and will accept respective revisions or amendments provided 
by the Sponsor. 
 
 
 
 
 
 
 
Principal Investigator Signature 
 
Date 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 
 
PLEASE RETAIN THE ORIGINAL SIGNED COPY FOR YOUR STUDY RECORDS 
 
 
 

 
 
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TABLE OF CONTENTS 
 
Page 
1.0 
SYNOPSIS ................................................................................................................6 
2.0 
GLOSSARY ............................................................................................................18 
3.0 
ETHICS ...................................................................................................................20 
4.0 
INTRODUCTION .....................................................................................................22 
5.0 
STUDY OBJECTIVE................................................................................................24 
5.1 
Primary Objectives ...............................................................................................24 
5.2 
Secondary Objectives ..........................................................................................24 
5.3 
Exploratory Objectives .........................................................................................24 
6.0 
ENDPOINTS ...........................................................................................................25 
6.1 
Primary Endpoints................................................................................................25 
6.2 
Secondary Endpoints ...........................................................................................25 
6.3 
Additional Measurements / Data Collected ...........................................................25 
7.0 
INVESTIGATIONAL PLAN.......................................................................................27 
7.1 
Overall Study Design and Plan – Description ........................................................27 
7.2 
Enrollment ...........................................................................................................27 
7.3 
Inclusion Criteria ..................................................................................................27 
7.4 
Exclusion Criteria .................................................................................................28 
7.5 
Prior and Concomitant Therapy ............................................................................29 
7.6 
Screening Failures ...............................................................................................29 
7.7 
Removal of Patients from the Study......................................................................29 
8.0 
STUDY PROCEDURES...........................................................................................31 
8.1 
Procedure Description(s)......................................................................................31 
8.2 
Visits ...................................................................................................................35 
8.2.1 
Visit 1 – Screening....................................................................................35 
8.2.2 
Visit 2 – Ablation Procedure Through Discharge (Visit 2B) .........................36 
8.2.3 
Visit 3 – 30-day Follow-up .........................................................................38 
8.2.4 
Visit 4 – 6-month Follow-up.......................................................................38 
8.2.5 
Visit 5 – 12-month Follow-up / End-of-Study ..............................................39 
8.2.6 
Unscheduled Visits ...................................................................................40 
9.0 
DATA MANAGEMENT AND INTEGRITY .................................................................41 
9.1 
Data Completion and Record Keeping..................................................................41 
9.2 
Medical Dictionary Coding....................................................................................43 
9.3 
Data Quality Assurance........................................................................................43 
9.4 
Protocol Deviations ..............................................................................................44 
10.0 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF 

 
 
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SAMPLE SIZE .........................................................................................................44 
10.1 Statistical and Analytical Plans .............................................................................44 
10.2 Study Design .......................................................................................................44 
10.3 Treatment Assignment .........................................................................................44 
10.4 Interval Windows .................................................................................................45 
10.5 Primary Endpoints................................................................................................45 
10.6 Levels of Significance ..........................................................................................45 
10.7 Analysis Sets .......................................................................................................45 
10.8 Sample Size Justification .....................................................................................45 
10.9 Analyses to be Conducted ...................................................................................46 
11.0 RISKS AND BENEFITS OF THE STUDY .................................................................48 
12.0 ADVERSE EVENTS ................................................................................................49 
12.1 Definitions............................................................................................................49 
12.2 Reporting Adverse Events....................................................................................50 
13.0 PRODUCT COMPLAINTS .......................................................................................52 
13.1 Product Complaint Definition ................................................................................52 
13.2 Reporting Product Complaints ..............................................................................52 
14.0 PUBLICATION PLAN...............................................................................................52 
15.0 APPENDICES .........................................................................................................53 
16.0 REFERENCE LIST ..................................................................................................55 
 
 

 
 
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1.0 SYNOPSIS 
 
 
Full title & protocol number 
A Multicenter Study of the NEUWAVE Flex Microwave 
Ablation System in the Ablation of Medically Inoperable 
Primary Soft Tissue Lesions of the Lung: An Initial Experience  
NEU_2017_06 
Short title 
NEUWAVE Flex Microwave Probe in Medically Inoperable 
Primary Soft Tissue Lesions of the Lung  
IDE/IND number  
N/A  
Sponsor 
NeuWave Medical, Inc. 
Indication 
Medically inoperable primary soft tissue lesions of the lung 
Study article description 
NEUWAVE Flex Microwave Ablation System and 
Accessories 
FLEX4 and FLEX6 probes 
ARM1 and ARM2 are two variations of the endoscopic 
support arm  
Regulatory classification 
Registered devices used in the clinical trials:  
Class 2: NEUWAVE Flex Microwave Ablation System and 
Accessories 
Class 2: FLEX4 and FLEX6 probes 
Class 1: ARM1 and ARM2 (endoscopic support arms) 
Study devices and 
descriptions 
NEUWAVE 
Flex 
Microwave 
Ablation 
System 
and 
Accessories (henceforth called NEUWAVE Flex Microwave 
Ablation System) are substantially equivalent to the marketed 
device, Certus 140 2.45 GHz Ablation System and 
Accessories. The device is designed for ablations of lesions 
in soft tissue in which the target tissue is accessed 
transbronchially.  
Two microwave ablation probes are available for use with the 
NEUWAVE Flex Microwave Ablation System: the FLEX4 and 
the FLEX6. They are comprised of a conical tip on the end of 
a flexible cable and a connector assembly. The probe with the 
sharper tip (FLEX6) is designed for easier tissue penetration 
while the probe with the less sharp tip (FLEX4) is designed 
for improved navigation. Both FLEX probe models are French 
gauge 6 (outer diameter of less than 2 mm) and 150 cm long. 
Both probe models have the same antenna design and 
ablation performance characteristics. 
ARM1 and ARM2 are two variations of the endoscopic 
support arm, which are designed to hold the Power 
Distribution Module (PDM) in a user-selected position that 

 
 
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allows the PDM and probe to move with the patient, greatly 
reducing the potential injury due to accidental probe 
movement. 
Study design 
Multicenter, single-arm 
Sample size 
No formal hypotheses are being tested in this study and 
hence a target sample size of 40 patients (with an 
approximate equal distribution of device use by interventional 
pulmonologists and thoracic surgeons) is deemed adequate 
for a preliminary investigation of the feasibility of this 
procedure as well as for providing sufficient information for 
appropriately sizing a subsequent study. 
Study population 
Adult patients with a medically inoperable primary soft tissue 
lesion of the lung ≤ 2 cm located in the outer two-thirds and 
not closer than 1 cm to the pleura. 
Outer two-thirds of the lung is defined as peripheral beyond 
the segmental airway, past the segmental bronchi, such that 
proximal endobronchial soft tissue lesions are avoided; soft 
tissue lesions should not be contiguous with the pleura. 
This study may include patients with operable lesions, but 
who elect not to have surgery. 
Geographic areas to be 
included 
United States  
Study duration 
Enrollment: 1 year 
Follow-up: 1 year 
Procedure(s) description 
Adult patients with a medically inoperable primary soft tissue 
lesion of the lung will have transbronchial microwave ablation 
performed using cone beam CT (computed tomography) 
scan for probe guidance and confirmation. 
A patient will have a lesion (“target lesion”) that meets the 
inclusion criteria upon entering the study. If a patient has 
more than one lesion, only one lesion may be treated during 
the ablation procedure (Visit 2A). If new non-target lesions 
meet the inclusion criteria, they may be treated. However, 
only one lesion (“target or new”) that meets the inclusion 
criteria may be ablated at any one time during the follow-up 
period of 12 months.  
Antibiotics must be administered prior to the ablation 
procedure. All ablations will be performed under general 
anesthesia via transbronchial approach by an interventional 
pulmonologist or thoracic surgeon. It is recommended that an 
interventional radiologist (IR) be present at all ablations. 
For those patients who specifically consent, the procedure 
may be filmed for training and research purposes (only 
applicable to selected patients). 
Convex probe endobronchial ultrasound (CP-EBUS) will be 
performed immediately prior to the ablation procedure to 

 
 
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establish disease stage certainty. A biopsy of the lung lesion 
may be done per the study site’s standard-of-care (SOC) 
procedures; however, it may not be done at the same time as 
the CP-EBUS and the ablation procedure. 
The size of the lesion will be measured and recorded on the 
day of ablation (Visit 2A). Afterwards, cone beam CT will be 
used to guide the microwave ablation probe to the target soft 
tissue lesion. Cone beam CT, which may be used with 
contrast (optional), will be used at three timepoints during the 
ablation process: (1) Pre-ablation: Just prior to inserting the 
probe into the soft tissue lesion, cone beam CT will be used 
to confirm soft tissue lesion details; (2) Intra-ablation: 
Immediately before the ablation, after the intrabronchial 
sheath has been retracted, cone beam CT will be used to 
confirm that the probe is in the intended location and, if not, 
repositioned and another scan will be taken. The physician 
will repeat this process, until the intended position is 
achieved; and, (3) Post-ablation: After completing the 
ablation, cone beam CT will be used to confirm that the 
ablation margins are adequate. If they are not adequate, the 
ablation application (with scans) should be repeated, if 
possible.  
The smallest distance in the ablation zone, as well as the 
distance from the edge of the ablation zone to the edge of the 
target lesion (i.e., the treatment margin), must be measured 
and captured in the clinical database. 
The Investigator will submit at least three cone beam CT 
scans for the day of the ablation to the central radiologist, as 
per the Central Radiology Review Manual. All cone beam CT 
scans (taken during the ablation procedure) and all 
conventional CT scans (taken during the post-ablation follow-
up visits) must be de-identified and sent in DICOM (digital 
imaging and communications in medicine) format, if possible, 
for central radiology review, via the Imaging Core Lab 
Services, LLC (ICLS) web portal. The central radiologist will 
produce multiplanar, volumetric, three-dimensional (3-D) 
images to independently assess the outcome of the ablation. 
The Sponsor will receive the full CT image sets of all patients. 
These image sets will be used to further the development of 
the NEUWAVE Flex Microwave Ablation System software. 
The software development will focus on increasing the ability 
to target the lesion, ensure accurate probe placement, and 
confirm ablation margins.  
The central radiologist will independently review all CT scans 
taken at Screening and throughout the clinical study to reduce 
the variability between investigators in assessing scans and 
to minimize potential bias. The central radiologist’s 
assessment will be used only for statistical analysis, while the 
Investigator’s assessment will be used for clinical decisions 

 
 
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for the treatment of patients in the study. Any discordance 
between Investigator’s assessment and 
the central 
radiologist’s assessment will be reported. If a positron 
emission tomography (PET) scan is taken during the 
follow-up period, the site must also perform the diagnostic CT 
as per protocol. 
The treatment goal is to achieve a complete ablation, which 
will require an adequate margin, immediately and one-month 
post-ablation, as defined by the treating physician, and as 
assessed by cone beam CT imaging. 
The Sponsor will provide a Product Development Specialist 
at every ablation to troubleshoot any technical issues with the 
NEUWAVE 
Flex 
Microwave 
Ablation 
System 
and 
Accessories. Additionally, the Sponsor will also provide a 
medical specialist experienced in this procedure for the 
treating physician to consult at each ablation. 
In addition to the Instructions for Use (IFU), the Sponsor will 
also provide a basic guide for performing a transbronchial 
microwave ablation with the flexible probe using the 
NEUWAVE Flex Microwave Ablation System. 
Post treatment follow-up will be carried out as per Table 1: 
Schedule of Assessments at the end of this synopsis.  
Primary objective 
The primary objective of the study is to evaluate the 
NEUWAVE 
Flex 
Microwave 
Ablation 
System 
and 
Accessories in transbronchial ablation procedures for adult 
patients with a medically inoperable primary soft tissue lesion, 
based on the following assessments: 
1. Device user experience survey 
2. Technical success 
3. Technique efficacy. 
Device user experience will be collected from the treating 
physician who will complete the User Experience Survey 
following each ablation procedure throughout the study, when 
applicable; the User Experience Survey is available as a 
separate document. The questionnaire includes, but is not 
limited to procedure workflow and the user’s assessment on 
ease/difficulty of using the device.  
The User Experience Survey will augment the Product 
Development Specialist’s understanding of the usability of the 
NEUWAVE Flex Microwave Ablation System and determine 
which enhancements, if any, are needed in the future.  
Technical success and technique efficacy will also be 
measured. 
Secondary objectives 
1. To evaluate safety through the monitoring of all 
device-related, procedure-related, and 
serious 
adverse events (SAEs) from start of ablation through 

 
 
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1-year post-ablation. 
2. To establish device and procedure effectiveness by 
following patients for 1-year post-ablation to ensure 
completeness and durability of treatment effect, 
based on standard endpoints in microwave ablation 
studies, as follows: 
a. Primary efficacy rate 
b. Secondary efficacy rate 
c. Target lesion recurrence 
3. To calculate length of hospital stay (LOS), measured 
from post-ablation to discharge. 
4. To calculate hospital readmission rate, defined as any 
readmission to the hospital within 30 days of the 
ablation procedure (Visit 2A).  
Exploratory objectives 
1. To assess the quality of life post microwave ablation 
of the lung throughout the 1 year ± 1 month follow-up 
period. 
2. To assess the level of pain during the initial 30 days 
± 7 days post-ablation.  
Primary endpoints 
• 
Device user experience: The data will come from the 
User Experience Survey, which will be completed by 
the treating physician following each ablation 
procedure. 
• 
Technical success, defined as: ablation of the target 
lesion according to the protocol and covered 
completely, with an adequate margin, as defined by 
the performing physician (that is, the ablation zone 
completely overlaps or encompasses the target lesion 
plus an ablative margin), as assessed by cone beam 
CT imaging, immediately following the procedure. 
• 
Technique efficacy, defined as: ablation of the target 
lesion according to the protocol and covered 
completely, with an adequate margin, as defined by 
the performing physician (that is, the ablation zone 
completely overlaps or encompasses the target lesion 
plus an ablative margin), as assessed using CT 
imaging at Visit 3, which is 30 days ± 7 days after the 
first ablation procedure. 

 
 
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Secondary endpoints  
The secondary endpoints, include the following:  
• 
Any complications attributable to the procedure, 
including all device-related, procedure-related, and 
SAEs, evaluated from the start of ablation through 
30 days ± 7 days post-ablation and from the start of 
ablation 
through 
end 
of 
follow-up 
(1-year 
post-ablation) or early discontinuation. 
• 
Primary efficacy rate, defined as: the percentage of 
target soft tissue lesions successfully eradicated 
following the first ablation procedure, as assessed 
using CT imaging. 
• 
Secondary efficacy rate, defined as: the percentage 
of soft tissue lesions that have undergone successful 
repeat ablation following identification of local soft 
tissue lesion progression, as assessed using CT 
imaging. 
• 
Target lesion recurrence, defined as reappearance of 
the lesion at the treated site, as assessed using CT 
imaging. 
• 
LOS, measured from post-ablation to discharge. 
• 
Hospital 
readmission 
rate, 
defined as 
any 
readmission to the hospital within 30 days.  
Exploratory endpoints 
• 
Quality of life (QOL) questionnaires utilizing the 
European Organization for Research and Treatment 
of Cancer (EORTC) QLQ-C30 and the lung-specific 
QLQ-LC13 to be completed at Screening (Visit 1), 
pre-ablation (Visit 2A), on Day 1 just prior to discharge 
(Visit 2B), and at all follow-up visits (Visit 3 through 
Visit 5). 
• 
Numeric Pain Rating Scale, to be completed at 
Screening (Visit 1), pre-ablation (Visit 2A), on Day 1 
just prior to discharge (Visit 2B) and at 30 days 
± 7 days post-ablation (Visit 3).  
Inclusion criteria 
1. Signed informed consent.  
2. Patients ≥ 18 years old. 
3. Performance status 
0-2 (Eastern Cooperative 
Oncology Group classification [ECOG]). 
4. Willing to fulfill all follow-up visit requirements. 
5. Medically inoperable primary soft tissue lesion of the 
lung or patient election not to have surgery. 
(Medically inoperable is defined per the following 
indicators: 
post op 
predictive FEV1 < 
40%; 
DLCO < 40%; hypoxemia or hypercapnia diabetes 
with end-organ damage; or severe cerebral, 
cardiovascular, peripheral vascular disease, or 
chronic heart disease). 

 
 
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6. A soft tissue lesion ≤ 2 cm in the outer two-thirds of 
the lung and not closer than 1 cm to the pleura. Lesion 
size must be measured with at least 2-dimensional 
(2D) imaging. Only one lesion meeting the inclusion 
criteria may be treated during the day of ablation 
(Visit 2A). However, additional primary disease 
lesions may be present on the day of ablation.  
 
(Outer two-thirds of the lung is defined as peripheral 
beyond the segmental airway, past the segmental 
bronchi, such that proximal endobronchial soft tissue 
lesions are avoided; soft tissue lesions should not be 
contiguous with the pleura). 
Exclusion criteria 
1. Scheduled concurrent procedure for the target soft 
tissue lesion other than those that are lung related. 
2. Pregnant or breastfeeding. 
3. Physical or psychological condition that would impair 
study participation. 
4. Patients with uncorrectable coagulopathy at time of 
screening. 
5. Patient 
with 
implantable 
devices, 
including 
pacemakers or other electronic implants. 
6. Prior pneumonectomy or bronchiectasis. 
7. Severe neuromuscular disease. 
8. Platelet count ≤ 50,000/mm3. 
9. ASA (American Society of Anesthesiologists) score 
of ≥ 4.  
10. Inability to tolerate anesthesia. 
11. Expected survival less than 6 months. 
12. Clinically significant hypertension. 
13. Chronic, continuous ventilator support, which uses bi-
level positive airway pressure (PAP) to improve lung 
function for severe conditions. (However, intermittent 
PAP, for non-pulmonary conditions, such as sleep 
apnea, is permitted.) 
14. Endobronchial soft tissue lesions proximal to the 
segmental airways. 
15. CP-EBUS lymph node sampling that results in a 
positive diagnosis of malignancy. 
16. Imaging findings of active pulmonary infection. 
17. The patient was judged unsuitable for study 
participation by the Investigator for any other reason. 

 
 
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Test product  
NEUWAVE Flex Microwave Ablation System 
Product 
Code 
Description 
NWF1US1N 
NEUWAVE Flex 
Microwave 
Ablation 
System, 120 Vac DR-000770 
FLEX6 
NEUWAVE Microwave Ablation Probe, 
6 French, 150cm DR-000899 
FLEX4 
FLEX4, NEUWAVE Microwave Ablation 
Probe, 6 French, 150cm DR-000900 
ARM1 
The Arm Endoscopic Support Arm, DR-
000674 
ARM2 
The Arm Endoscopic Support Arm, Dovetail 
Mount, DR-000980 
Safety assessments 
Patients will be evaluated for AEs and SAEs at every study 
visit until the end-of-study, which is 1 year following the first 
ablation procedure. 
Statistical analysis  
Summary statistics will be provided for all endpoints 
collected. Analyses described below will be performed on the 
pooled set of 40 patients, as well as summarized separately 
for the set of patients treated by interventional pulmonologists 
and by thoracic surgeons. No comparisons between these 
groups are planned.  
Responses to the User Experience Survey will be 
summarized with descriptive statistics appropriate for 
categorical or continuous variables.  
The number and percentage of patients achieving technical 
success will be summarized and a 95% confidence interval 
will be estimated. Technique efficacy, as well as primary and 
secondary efficacy rates and hospital readmission rate, will 
be summarized in a similar manner. Local soft tissue lesion 
recurrence rates will be estimated using the Kaplan-Meier 
method and 95% confidence intervals will be provided. 
The number and percentage of patients experiencing AEs 
from the start of ablation (Visit 2A) to Visit 3 (the first post-
ablation visit) will be summarized by MedDRA preferred term 
and system organ class. A similar summary will also be 
provided for AEs that are device related and procedure 
related, and all SAEs. Ninety-five percent confidence 
intervals may be provided for pre-specified AEs of interest. 
These summaries will be repeated for the entire observation 
period (Visit 2A through study completion).  
EORTC QOL questionnaires and Numeric Pain Rating Scale 
scores will be summarized with methodology consistent to the 

 
 
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recommendations of the specific survey. Additional endpoints 
will be summarized with descriptive statistics.  
Interim analysis 
There are no plans for interim analyses, whose intent would 
be to stop the study early or to modify the study design.  
Two analysis timepoints are planned. The first analysis will 
occur after all patients within a treatment group (interventional 
pulmonologist or thoracic surgeon) complete Visit 3 (30 days 
± 7 days after the first ablation procedure). This analysis will 
provide a summary of the User Experience Survey, technical 
success, technique efficacy, and safety through Visit 3. When 
the second group completes this timepoint, results will be 
summarized for that group and subsequently in total. The 
second analysis timepoint will be at the completion of the 
study. 
Ongoing review 
The Sponsor will also review complications periodically, as 
per the Safety Management Plan. Complications that may 
occur during and after microwave lung ablations may include 
(but are not limited to) the following:  
1. pneumothorax (requiring tube drainage)  
2. hemorrhage, bleeding requiring medical intervention  
3. post-ablation syndrome  
4. pain  
5. pleural effusion, requiring tube drainage  
6. pneumonia  
7. abscess  
8. infection  
9. bronchopleural fistula. 
A report of death will stop enrollment and require an 
investigation to determine if the death is related to the 
ablation procedure or device. If the death is deemed not 
related to the ablation procedure or device, the study may 
resume enrollment. 
Data 
Safety 
Monitoring 
Board 
A Data Safety Monitoring Board (DSMB) will be appointed by 
the Sponsor to review, on a regular basis, safety data from 
the study. The DSMB will advise the Sponsor regarding the 
continuing safety of patients and those yet to be recruited to 
the study. Based on accumulating data from the study, the 
DSMB may recommend whether to continue, suspend, 
modify, or stop the study. 
At the conclusion of the review of all 40 patients, the DSMB 
will also give a final assessment of the safety of the 
procedure. The composition, responsibilities, frequency of 
DSMB meetings, handling of emergency situations, and 
documentation of DSMB meetings is specified in the DSMB 
Charter. 
Schedule of Assessments 
See Table 1 on the next page. 
 

 
 
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Table 1: Schedule of Assessments 
 
 
 
 
Visit No. 
Visit 1: 
Visit 2A 
Visit 2B 
Visit 3 
Visit 4 
Visit 5 
Unscheduled 
Visit23 
Visit 
Screening 
Ablation Discharge22 Follow-up Follow-up Follow-up 
Interval Windows:   
Study Assessments 
≤ 30 days 
preablation 
Day 0 
Ablation 
Day 1 
30 days 
(± 7 days) 
6 months 
(±1 month) 
12 months 
(±1 month) 
Study Assessments 
Informed consent1 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical/surgical history/ASA score2  
X 
 
 
 
 
 
 
ECOG status and BMI3 
X 
X* 
X 
X 
X 
X 
 
Concomitant medications4  
X 
X 
X 
X 
X 
X 
X 
Serum pregnancy test 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria5  
X 
X* 
 
 
 
 
 
EORTC QOL6 
X 
X 
X 
X 
X 
X 
 
Numeric Pain Rating Scale 
X 
X* 
X 
X 
 
 
 
Administer antibiotics 
 
X* 
 
 
 
 
 
Convex Probe (CP)-EBUS7 
 
X 
 
 
 
 
 
Lesion details via CT  
X8 
X9 
 
X10 
X10 
X10 
 
Pulmonary function tests (PFTs)11 
X 
 
 
 
X 
X 
 
CBC with differentials 
X 
 
 
X 
X 
X 
 
Coagulation tests12  
X 
 
 
X 
X 
X 
 
Relevant genetic markers13  
X 
 
 
 
 
 
 
Ablation procedure details14 
 
X 
 
 
 
 
 
Device user experience15 
 
X 
 
 
 
 
 
Technical success assessment16 
 
X 
 
 
 
 
 
Technique efficacy assessment17 
 
 
 
X 
 
 
 
Concomitant procedures (all)  
 
X 
X 
X 
X 
X 
X 
AEs/SAEs18 
 
X 
X 
X 
X 
X 
X 
Length of hospital stay19/ UB-04 data20 
 
 
X 
 
 
 
 
Assess if hospital readmission 21 
 
 
 
X 
 
 
 

 
 
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* Indicates assessments should be done prior to the ablation procedure.  
 
1. 
Informed consent consists of the general study consent, consent to share data for the Time and Power predictive analytics study, and consent for filming the 
ablation procedure (the latter is applicable only to selected patients). 
2. 
Medical history, including date of diagnosis of soft tissue lesion under study, radiation history, and smoking status. 
3. 
Evaluate ECOG performance status, and collect height and body weight for body mass index (BMI). 
4. 
Record all prior medications (taken within 30 days of Visit 2) and all concomitant medications taken throughout the study, including but not limited to 
chemotherapy, steroids, anti-inflammatories, NSAIDs, hormonal therapy, homeopathic/natural medications, nutritional supplements, and antibiotics. Do not 
record components of the anesthesia medications used for the ablation procedure. 
5. 
Review the inclusion and exclusion criteria prior to performing the ablation procedure. 
6. 
QOL questionnaires EORTC QLQ-C30 and the lung-specific QLQ-LC13. The questionnaires may be administered over the phone, as needed. 
7. 
Convex probe EBUS (CP-EBUS) must be performed immediately prior to the ablation procedure to establish disease stage certainty and confirm that the 
lung disease has not spread to other parts of the body, such as to the lymph nodes. A biopsy of the lung lesion may be done per the study site’s SOC; 
however, it may not be done at the same time as the CP-EBUS and ablation procedure. 
8. 
CT scan of the lung is used at Screening to determine soft tissue lesion details (eg, size, lesion type, location, shape). Lesion size must be measured with 
at least 2-dimensional (2D) imaging. A patient may enter the study with only one lesion.  
9. 
Measure and record the size of the lesion on the day of ablation (Visit 2A). Afterwards, use cone beam CT to guide the microwave ablation probe to the 
target soft tissue lesion and insert the probe into the lesion. Scanners should yield high resolution images (volumetric thin sections) that are adequate for 
multiplanar reconstruction and which will allow for optimal visualization of the lesion. Cone beam CT will be used at 3 timepoints during the ablation process: 
(1) Pre-ablation: Just prior to inserting the probe into the soft tissue lesion, use cone beam CT to confirm soft tissue lesion details; (2) Intra-ablation: 
Immediately before the ablation, after the intrabronchial sheath has been retracted, use cone beam CT to confirm that the probe is in the intended location 
and, if not, reposition the probe and take another scan. The physician should repeat this process, until the intended position is achieved; and, (3) Post-
ablation: After completing the ablation, use cone beam CT to confirm that the ablation margins are adequate. If they are not adequate, the ablation application 
(with scans) should be repeated, if possible. The smallest distance in the ablation zone, as well as the distance from the edge of the ablation zone to the 
edge of the target lesion (i.e., the treatment margin), must be measured and captured in the clinical database. Send the pre-ablation, intra-ablation, and 
post-ablation scans in DICOM format, where possible, to the central radiologist for independent review; if more than 1 scan was taken at any of the 3 
timepoints, send only the final one. All scans will be submitted via the ICLS web portal. Refer to the Central Radiology Review manual for more details. The 
Sponsor will receive the full CT image sets of all patients. 
10. CT scan of the lung is used at every follow-up visit to determine soft tissue lesion details (eg, size, lesion type, location, shape) and to assess local soft 
tissue lesion control. The scanners should yield high resolution images (volumetric thin sections) that are adequate for multiplanar reconstruction and which 
will allow for optimal visualization of the lesion. Submit the scans in DICOM format, where possible, to the central radiologist for independent review. If PET 
scan is taken during follow-up, the site must also perform the diagnostic CT as per protocol. 
11. PFTs should include spirometry, diffusion capacity (DLCO), lung volume tests, 6-minute walk or pulse oximetry, and fractional exhaled nitric oxide (FeNO) 
tests. 

 
 
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12. Coagulation tests, including APTT, INR, PT, PTA, and PTT. 
13. Tests for any genetic markers relevant to the lesion, if done per site’s SOC. 
14. Ablation procedure details include, but are not limited to, the following: date and time of procedure, anatomical location of ablations, number of ablation 
cycles and power used for each ablation, guidance method used, number of cone beam CT scans performed for probe placement and margin assessment, 
number of probe placement attempts per ablation, type of probes used, type of anesthesia, duration of procedure (the time when the bronchoscope enters 
the endotracheal tube to the time when the last cone beam CT scan is taken) and radiation exposure from CT scans. Some of the above ablation procedure 
details will be provided to the site via a report generated from NeuWave Medical’s Call Home Database. The study site will review the report and enter the 
procedure details into the clinical database, as applicable. 
15. Device user experience, to be collected from the treating physician who will complete the User Experience Survey following each ablation procedure 
throughout the study, when applicable. 
16. Technical success, defined as: ablation of the target lesion according to the protocol and covered completely, with an adequate margin as defined by the 
performing physician (that is, the ablation zone completely overlaps or encompasses the target lesion plus an ablative margin). Technical success will be 
assessed by cone beam CT imaging, immediately following the procedure. 
17. Technique efficacy, defined as: ablation of the target lesion according to the protocol and covered completely, with an adequate margin as defined by the 
performing physician (that is, the ablation zone completely overlaps or encompasses the target lesion plus an ablative margin). Technique efficacy will be 
assessed using CT imaging at Visit 3. 
18. All AEs and SAEs will be collected at each visit, from the start of ablation at Visit 2A, through the end of study or early discontinuation. 
19. Length of hospital stay (LOS), measured from post-ablation to discharge.  
20. The study site must redact private health information from the UB-04 data prior to sharing with Sponsor. Information will be identified only with the patient ID 
number. 
21. Record readmission to any hospital for any reason within 30 days of the ablation. The Investigator will assess the reason for the ad mission and capture the 
reason in the clinical database. 
22. After the ablation procedure, the patient will be observed for up to 23 hours and then discharged, except in cases where the Investigator deems it is necessary 
for the patient to remain hospitalized. 
23. Record reason for unscheduled visit, as well as AEs (if applicable), and any updates to concomitant medications and concomitant procedures. 
 
. 

 
 
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2.0 GLOSSARY 
Table 2. Acronyms/ Abbreviations 
 
Acronyms/ 
Abbreviations 
Terms 
AE 
adverse event 
ASA 
American Society of Anesthesiologists 
BMI 
body mass index 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CP-EBUS 
convex probe endobronchial ultrasound 
CT 
computed tomography 
CTC 
Common Terminology Criteria 
DICOM 
digital imaging and communications in medicine 
DLCO 
diffusing [capacity of the] lung [for] carbon monoxide 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
EC 
ethics committee 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ENB 
electromagnetic navigation bronchoscopy 
EORTC 
European Organization for Research and Treatment of Cancer 
EWC 
extended working channel 
FeNO 
fractional exhaled nitric oxide (test) 
FEV1 
forced vital capacity (FVC) 
GCP 
Good Clinical Practices 
ICF  
informed consent form 
ICLS 
Imaging Core Lab Services, LLC 
ID 
identification 
IFU 
instructions for use 
INR 
international normalized ratio 

 
 
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Acronyms/ 
Abbreviations 
Terms 
IRB 
institutional review board 
LOS  
length of (hospital) stay 
MedDRA 
Medical Dictionary for Regulatory Activities 
NSAIDs 
nonsteroidal anti-inflammatory drugs 
PAP 
positive airway pressure 
PDM 
power distribution module 
PET 
positron emission tomography 
PFT 
pulmonary function test 
PI 
principal investigator 
PTA 
plasma thromboplastin antecedent 
PTT 
partial prothrombin time 
QOL 
quality of life 
SAE 
serious adverse event 
SOC 
standard-of-care 
 
 
 

 
 
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3.0 ETHICS 
Institutional Review Board/Ethics Committee 
Participating investigators will ensure that this protocol, Informed Consent Form (ICF), and if 
applicable, any protocol amendments or other written information provided to the subjects that 
assist in the decision to participate are reviewed by an Institutional Review Board (IRB) or 
Ethics Committee (EC) that complies with governmental requirements. The approving IRB/EC 
will be responsible for the initial and continuing review and approval of this clinical 
investigation. Participating investigators will be required to promptly report new protocol 
amendments and new ICFs to the IRB/EC as required by the IRB/EC’s policies. Additionally, 
investigators will be required to refrain from making any changes in the clinical investigation 
plan without Sponsor and IRB/EC approval of an amended protocol, except where necessary 
to eliminate apparent immediate hazards to study subjects or others. 
Applicable Regulations  
This study will be conducted in compliance with Good Clinical Practice and in accordance with 
the Declaration of Helsinki, as well as any other applicable local and country regulatory 
requirements. 
Subject Information and Consent  
Regulations concerning the protection of subjects require that informed consent be obtained 
before a subject may participate in any clinical investigation. Screening assessments that are 
part of standard-of-care (SOC) may occur prior to consent; however, the data may not be 
collected for study purposes until the ICF has been signed by the subject.  
An IRB/EC approved informed consent must be sought from each subject and must be 
appropriately documented in the subject’s medical record prior to initiating the study. It is the 
Investigator’s responsibility to obtain written informed consent from the subject, however, the 
Investigator may delegate this responsibility if appropriately documented.  
The informed consent process involves the following: giving a subject adequate information 
concerning the study, providing adequate time for the subject to consider all available options, 
responding to the subject’s questions, ensuring that the subject has comprehended this 
information and finally, obtaining the subject’s written consent to participate in this study. All 
subjects in this study should be completely informed about the purpose, risks, benefits, and 
other pertinent details of this study. The informed consent process is careful to avoid the 
perception of any coercion or undue influence on, or inducement of, the subject to participate, 
and does not waive or appear to waive the subject's legal rights. The ICF is presented in 
native, non-technical language that is understandable to the subject. 
Prior to a subject’s participation in this study, an ICF will be signed and dated by the subject 
and person who conducted the consent discussion. The subject will be provided a copy of the 
signed ICF. The ICF and any other written materials provided to the subject to assist in the 
decision to participate must be revised whenever new information becomes available that may 
be relevant to their willingness to participate or continue participation in this study. Revision to 
the ICF and other written materials will receive IRB/EC approval bef ore implementation. Each 
subject will be required to sign any amended ICF (as required by the IRB/EC) and will receive 
a copy of the signed ICF.  
 
 
 

 
 
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ADMINISTRATIVE REQUIREMENTS 
This study is sponsored by NeuWave Medical, Inc. and will be conducted in approximately 4 
to 8 study sites in the United States under a single protocol approved by each participating 
site’s IRB/EC prior to implementation. The principal investigator at each study site must be 
either an interventional pulmonologist or thoracic surgeon qualified by education, experience, 
and training to perform the study procedure and to assume responsibility for the conduct of 
this study. 
The Data Management and Biostatistics groups of NeuWave Medical, Inc. will be responsible 
for the analysis of data from this protocol. An electronic data capture (EDC) system will be 
utilized by study site personnel to transfer study data from source records (the first point of 
clinical data capture) onto common electronic case report forms (eCRFs). This system is a 
web-based, secure electronic software application (Medidata® Rave, 350 Hudson Street, 9th 
Floor, New York, New York, 10014). This system was designed and is developed and 
maintained by Medidata in a manner that is compliant with national and international Good 
Clinical Practice (GCP) data protection/data privacy and electronic record/electronic signature 
(e.g., 21 CFR Part 11) regulatory requirements.  
Protocol Modifications 
All protocol amendments must be issued by the Sponsor, signed and dated by the Investigator, 
and should not be implemented without prior IRB/EC approval, except where necessary to 
eliminate immediate hazards to the subjects or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone number). 
The Investigator reports the protocol amendments to the IRB/EC as per their local 
requirements. 
 
 

 
 
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4.0 INTRODUCTION 
There is clinical and economic demand for a minimally invasive treatment of pulmonary 
soft tissue lesions where tissue sparing is maximized, morbidity of the procedure is 
minimized, and the quality of care is most cost effective. Lung interventionalists desire a 
non-surgical approach that could allow both diagnosis and treatment in the shortest time 
frame possible while providing a proven durable effect. The flexible ablation platform 
provides a first-of-kind, minimally invasive, tissue-sparing bronchoscopic approach to 
lung tissue ablation.1 
This study will establish the first experience with the use of the NEUWAVE Flex 
Microwave Ablation System in transbronchial ablation procedures. This study will also 
provide indications of the durability of ablation of soft tissue lesions with NEUWAVE Flex 
Microwave Ablation System. 
The NEUWAVE Flex Microwave Ablation System and the FLEX4 and FLEX6 probes 
being used in this study are unmodified from those cleared by the FDA per K163118. The 
device is indicated for the ablation (coagulation) of soft tissue, which is a general purpose 
indication. The 510(k) clearance indicates that the device is safe and effective for this 
general indication for use, but the device is considered a tool for use by physicians, and 
is not a treatment for any specific disease or condition.  
In the 510(k) and the device labeling, additional guidance about the use the device is 
provided, specifically: 
The FLEX is designed to be used in target ablation. Target ablation involves 
placing a probe into a substantial target and then ablating for up to several 
minutes until the target tissue is necrotic. The FLEX is designed for ablations 
in soft tissue in percutaneous (via an introducer) procedures, open surgical 
procedures, and procedures in which the target tissue is accessed via a lumen 
or scope such as an endoscope, bronchoscope, or laparoscopic port. 
In this protocol, the target tissue will be accessed using the flexible probe via an 
endobronchial approach. 
In the device labeling, ex-vivo ablation size data is provided for lung, liver, and kidney 
tissue as a guide to users. 
Although the ablation of lung lesions that are accessed transbronchially was anticipated 
and accounted for in the design and development of this device, the specific application 
of transbronchial ablation of lung lesions has not been reported to date in human subjects. 
Per FDA Guidance: Use of Real World Evidence to Support Regulatory Decision Making 
for Medical Devices, this study is considered IDE Exempt because: 
1. The device is being used in the normal course of medical practice under the authority 
of a healthcare provider.  
2. The protocol does not dictate or influence treatment decisions. 
3. The gathering of data per the protocol does not influence treatment decisions. All data 
gathered per this protocol are data that are normally collected and documented for 
ablation procedures. 
For pulmonary soft tissue lesions, microwave ablation is believed to be a better treatment 
choice than radiofrequency (RF) ablation. Aerated lung is characterized by high 
impedance to electric current flow and poor heat transfer compared with most solid 
organs. The high impedance of normal lung tissue surrounding a soft tissue lesion can 
reduce power delivery, whereas poor thermal diffusion limits growth of the ablation zone.2 

 
 
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3 
It should be noted that nearly all previous studies of microwave ablation passed the 
ablation probe into the lungs percutaneously, that is, through a needle puncture of the 
skin. In our proposed study, the microwave ablation probe is guided through the bronchial 
airway into the outer two-thirds of the lung.  
A clinical study in humans found that the endobronchial approach limits complications. 
The rates of common complications were generally lower among those who had 
undergone endobronchial lung biopsy compared with those who had undergone 
percutaneous lung biopsy. The complications included pneumothorax, pleural effusion, 
hemoptysis, infection, pain, and bronchopleural fistula. 4 The endobronchial access, 
versus transthoracic penetration, of the probe is designed to minimize the risk of 
bronchopleural fistula. In addition, it is expected that ablations with the NEUWAVE Flex 
Microwave Ablation System will be a relatively quick procedure by overcoming perfusion 
and produce an effective volume to ablate the soft tissue lesions with a clinically beneficial 
margin.5 
This study will use high resolution cone beam and conventional CT (computed 
tomography) imaging to assess the outcome of the ablation. Scanners should yield high 
resolution images (volumetric thin sections) that are adequate for multiplanar 
reconstruction and which will allow for optimal visualization of the lesion. All scans must 
be de-identified and sent in DICOM (digital imaging and communications in medicine) 
format, where possible, to the central radiologist, via the Imaging Core Lab Services, LLC 
(ICLS) web portal. The central radiologist will produce multiplanar, volumetric, three-
dimensional (3-D) images to independently assess the outcome of the ablation. The 
Sponsor will receive the full CT image sets of all patients. These image sets will be used 
to further the development of the NEUWAVE Flex Microwave Ablation System software. 
The software development will focus on increasing the ability to target the lesion, ensure 
accurate probe placement, and confirm ablation margins. Data will be held until 
development of the software is completed. 
If a positron emission tomography (PET) scan is taken during the follow-up visits, the site 
must also perform the diagnostic CT as per protocol.  
 
 
 

 
 
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5.0 STUDY OBJECTIVE 
5.1 Primary Objectives 
The primary objective of the study is to evaluate the NEUWAVE Flex Microwave Ablation 
System in transbronchial ablation procedures for adult patients with a medically 
inoperable primary soft tissue lesion, based on the following assessments: 
a. Device user experience survey 
b. Technical success 
c. Technique efficacy 
Device user experience will be collected from the treating physician who will complete the 
User Experience Survey following each ablation procedure throughout the study, when 
applicable; the User Experience Survey is available as a separate document. The 
questionnaire will focus on procedure workflow and the user’s assessment on 
ease/difficulty of using the device. The device user experience will augment the Product 
Development Specialist’s understanding of the usability of the Flex system and determine 
which enhancements, if any, are needed. 
5.2  Secondary Objectives 
The secondary objectives are the following: 
1. To evaluate safety through the monitoring of device-related and procedure-related 
advserse events (AEs) and all serious adverse events (SAEs), from start of 
ablation through 1-year post-ablation. 
2. To establish device and procedure effectiveness by following patients for 1-year 
post-ablation to ensure completeness and durability of treatment effect, based on 
standard endpoints in microwave ablation, as follows: 
a. Primary efficacy rate 
b. Secondary efficacy rate 
c. Local soft lesion recurrence 
d. Length of hospital stay (LOS) 
e. Hospital readmission rate. 
3. To calculate length of hospital stay (LOS), measured from post-ablation to 
discharge. 
4. To calculate hospital readmission rate, defined as any readmission to the hospital 
within 30 days of the first ablation procedure (Visit 2A). 
 
5.3 Exploratory Objectives 
The exploratory objectives are the following: 
1. To assess the quality of life post microwave ablation of the lung throughout the 
1 year ± 1 month follow-up period. 
2. To assess the level of pain during the initial 30 days ± 7 days post-ablation. 

 
 
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6.0 ENDPOINTS 
6.1 Primary Endpoints 
The primary endpoints include the following: 
• 
Device user experience: The data will come from the User Experience Survey, 
which will be completed by the treating physician following each ablation 
procedure. 
• 
Technical success, defined as: ablation of the target lesion according to the 
protocol and covered completely, with an adequate margin, as defined by the 
performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus an ablative margin), as assessed by cone 
beam CT imaging, immediately following the procedure. 
• 
Technique efficacy, defined as ablation of the target lesion according to the 
protocol and covered completely, with an adequate margin, as defined by the 
performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus and ablative margin). Technique efficacy will 
be assessed using CT imaging at Visit 3, which is 30 days ± 7 days after the first 
ablation procedure.  
6.2 Secondary Endpoints 
The secondary endpoints include the following:  
• 
Any complications attributable to the procedure, including all device-related, 
procedure-related, and serious adverse events (SAEs), evaluated from the start of 
ablation through 30 days ± 7 days post application of ablation and from the start of 
ablation through end of follow-up (1-year post-ablation) or early discontinuation. 
• 
Primary efficacy rate, defined as the percentage of target soft tissue lesions 
successfully eradicated following the ablation procedure, as assessed using CT 
imaging. 
• 
Secondary efficacy rate, defined as the percentage of soft tissue lesions that have 
undergone successful repeat ablation following identification of local soft tissue lesion 
progression, as assessed using CT imaging. 
• 
Target lesion recurrence, defined as reappearance of the lesion at the treated site, as 
assessed using CT imaging. 
• 
Length of stay, measured from after the ablation procedure until the patient is 
discharged home. 
• 
Hospital readmission rate, defined as any readmission to the hospital within 30 days.  
6.3 Additional Measurements / Data Collected 
• 
Patient demographics and baseline characteristics. 
• 
Quality of life (QOL) and pain. 
• 
Relevant medical and surgical history. 
• 
Soft tissue lesion details (size, lesion type, location, shape). Ablation procedure 
details, including the following: 
- Date and time of the ablation procedure. 

 
 
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- Anatomical location of ablations of the target lesion. 
- Number of ablation cycles and power used for each ablation of the target 
lesion. 
- Guidance method used. 
- Number of cone beam CT scans performed for probe placement and margin 
assessment. 
- Number of probe placement attempts per ablation. 
- Type of probes used. 
- Type of anesthesia. 
- Duration of procedure, measured as the time when the bronchoscope enters 
the endotracheal tube to the time when the last cone beam CT scan is taken. 
- Radiation exposure from CT scans. 
 
Note: Some of the above ablation procedure details will be provided to the site via 
a report generated from NeuWave Medical’s Call Home Database. The study site 
will review the report and enter the procedure details into the clinical database. 
 

 
 
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7.0 INVESTIGATIONAL PLAN 
7.1 Overall Study Design and Plan – Description 
This is a multicenter, single-arm study for NEUWAVE Flex Microwave Ablation System in 
the ablation of soft tissue lesions of the lung for medically inoperable patients or those 
who elect not to have surgery. An experienced interventional pulmonologist or thoracic 
surgeon will determine whether a patient is “medically inoperable.” Indicators defining 
medically inoperable are, as follows: post-op predictive FEV1 < 40%; DLCO < 40%; 
hypoxemia or hypercapnia diabetes with end-organ damage; or, severe cerebral, 
cardiovascular, peripheral vascular disease, or chronic heart disease. 
Prospective patients will be informed about the nature of the research, given the ICF to 
read, and if the patient understands the content, will be asked to provide consent by 
signing the ICF. Individuals scheduled for microwave ablation of the lung will be enrolled 
after providing informed consent and meeting study entry criteria. Patients will be followed 
for approximately 1 year following the first ablation procedure for safety and efficacy 
outcomes.  
Enrollment will continue until approximately 20 patients ablated by interventional 
pulmonologists and approximately 20 patients ablated by thoracic surgeons complete 
Visit 3 (30 days ± 7 days after the first ablation procedure). Only participants who 
withdraw or are terminated prior to the planned intrabronchial flexible probe ablation 
procedure will be replaced. 
The Sponsor will provide a Product Development Specialist at every ablation to 
troubleshoot any technical issues with the NEUWAVE Flex Microwave Ablation System. 
The Sponsor will also provide a guide for performing a transbronchial microwave ablation 
with the flexible probe using the NEUWAVE Flex Microwave Ablation System. 
Adult patients with a medically inoperable primary soft tissue lesion of the lung will have 
transbronchial microwave ablation performed using cone beam CT scan.  
To reduce the variability between investigators in assessing the scans and to minimize 
potential bias, the central radiologist will review all CT scans (conventional and cone 
beam) taken at Screening and throughout the clinical study.  
The study will end when all patients have completed the 12-month, post-ablation follow-up 
period or have withdrawn early.  
7.2 Enrollment 
A target total of approximately 40 patients, with an approximate equal distribution of 
device use by interventional pulmonologists and thoracic surgeons, will be enrolled 
across multiple study sites in the United States. A subject who signs the consent is 
considered screened and once treated they are considered enrolled into the study.  
7.3 Inclusion Criteria 
Patients satisfying the following criteria will be eligible to participate in this study: 
1. Signed informed consent.  
2. Patients ≥ 18 years old. 
3. Performance status 0-2 (Eastern Cooperative Oncology Group classification 
[ECOG]). 

 
 
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4. Willing to fulfill all follow-up requirements. 
5. Medically inoperable primary soft tissue lesion of the lung or patient election not to 
have surgery.  
(Medically inoperable is defined per the following indicators: post-op predictive 
FEV1 < 40%; DLCO < 40%; hypoxemia or hypercapnia diabetes with end-organ 
damage; or severe cerebral, cardiovascular, peripheral vascular disease, or 
chronic heart disease.) 
6. A soft tissue lesion ≤ 2 cm in the outer two-thirds of the lung and not closer than 
1 cm to the pleura. Lesion size must be measured with at least 2-dimensional (2D) 
imaging. Only one lesion meeting the inclusion criteria may be treated during the 
day of ablation (Visit 2A). However, additional primary disease lesions may be 
present on the day of ablation.   
(Outer two-thirds of the lung is defined as peripheral beyond the segmental airway, 
past the segmental bronchi, such that proximal endobronchial soft tissue lesions 
are avoided; soft tissue lesions should not be contiguous with the pleura.) 
7.4 Exclusion Criteria 
Patients who meet any of the following criteria will not be eligible to participate in this 
study: 
1. Scheduled concurrent procedure for the target soft tissue lesion other than those 
indicated by the study protocol. 
2. Pregnant or breastfeeding. 
3. Physical or psychological condition that would impair study participation. 
4. Patients with uncorrectable coagulopathy at time of screening. 
5. Patient with implantable devices, including pacemakers or other electronic 
implants. 
6. Prior pneumonectomy or bronchiectasis. 
7. Severe neuromuscular disease. 
8. Platelet count ≤ 50,000/mm3. 
9. ASA (American Society of Anesthesiologists) score of ≥ 4.  
10. Inability to tolerate anesthesia. 
11. Expected survival less than 6 months. 
12. Clinically significant hypertension. 
13. Chronic, continuous ventilator support, which uses bi-level positive airway pressure 
(PAP) to improve lung function for severe conditions. (However, intermittent PAP 
for non-pulmonary conditions, such as sleep apnea, is permitted.) 
14. Endobronchial soft tissue lesions proximal to the segmental airways. 
15. Convex probe EBUS (CP-EBUS) lymph node sampling that results in a positive 
diagnosis of malignancy. 
16. Imaging findings of active pulmonary infection. 

 
 
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17. The patient was judged unsuitable for study participation by the Investigator for any 
other reason.   
7.5 Prior and Concomitant Therapy 
Patients may continue with their current medical care throughout the duration of the study, 
including medications. All concomitant medications will be recorded on the relevant eCRF 
page. Do not record components of the anesthesia medications used for the ablation 
procedure. 
7.6 Screening Failures 
All patients signing consent who do not meet the inclusion and exclusion criteria or who 
do not have the ablation procedure initiated, will be recorded as screen failures. The 
relevant eCRF pages (demographics, reason for screen failure) will be completed for all 
screen failure patients and thereby the data will be included in the study database. 
7.7 Removal of Patients from the Study 
In accordance with the current revision of the Declaration of Helsinki and the Code of 
Federal Regulations, a patient has the right to withdraw from the study at any time for any 
reason without prejudice to his/her future medical care by the physician or the institution. 
Should a patient (or patient’s legally authorized guardian/representative) decide to 
withdraw from the study, all efforts will be made to collect all AEs they may have 
experienced. Patients who withdraw or are terminated prior to the ablation procedure will 
be replaced. Enrollment will continue until approximately 20 patients have been ablated 
by interventional pulmonologists and approximately 20 patients have been ablated by 
thoracic surgeons. Only participants who withdraw or are terminated prior to the planned 
intrabronchial flexible probe ablation procedure will be replaced. 
Participation may be terminated prior to completing the study for any of the reasons listed 
below (reasons that do not fit the categories below will be documented as “other”).  
Withdrawal of Consent: 
If a patient chooses to withdraw early from the study, the eCRF completion page should 
be completed. When a patient’s participation is terminated prior to completing the study, 
the reason for withdrawal is to be documented on the eCRF and in the source 
documentation.  
Ablation: 
The Investigator may withdraw a patient during the ablation procedure for any reason, 
including the following reasons: 
1. Inability of Investigator to locate and target the soft tissue lesion. 
2. Inability of patient to tolerate the anesthesia. 
Death: 
When available, the cause of death should be documented.  

 
 
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Lost to follow-up: 
All patients should be encouraged to return for protocol required clinic visits for evaluation 
during the study follow-up period. If a patient is unable to return for a clinic visit or unable 
to be contacted by telephone, attempts to contact the patient should be documented in 
the source documents. Only after failing to contact the patient at the final follow-up visit, 
the patient will be considered lost to follow-up and the primary reason for early termination 
will be completed in the eCRF. 
Site Termination or Study Termination: 
The Sponsor may terminate a site or study at any time. When this occurs, all patients at 
the site will be withdrawn and documented as “early termination.” Reasons for site or 
study termination may include, but are not limited to, the following:  
• 
Administrative concerns (e.g., inadequate patient enrollment, 
investigator/institution non-compliance, change of business strategy, etc.). 
• 
Safety issues, including those due to non-compliance, which substantially affect 
the risk-to-benefit ratio of the study patients at a site or for the study as a whole. 
• 
Futility: It is evident that the endpoint cannot be reached given the study design 
and number of enrolled participants. 
• 
Regulatory body mandate(s). 
The Investigator has the right to terminate participation in the study at any time (e.g., for 
safety or inability to enroll patients). Should termination of a site be necessary, the 
Sponsor will provide procedures for termination. 
 

 
 
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8.0 STUDY PROCEDURES 
8.1 Procedure Description(s) 
Adult patients with medically inoperable primarily soft tissue lesions of the lung will have 
a transbronchial microwave ablation performed using cone beam CT scan. The 
Investigator will determine, with the help of imaging, whether a patient is suitable for 
ablation therapy. Potential candidates for microwave ablation will also undergo CBC, 
coagulation tests (APTT, INR, PT, PTA, PTT), as well as PFTs (spirometry, diffusion 
capacity [DLCO], lung volume tests, 6-minute walk or pulse oximetry, and fractional 
exhaled nitric oxide tests [FeNO]) prior to the procedure to ensure that they are adequate 
candidates for transbronchial microwave ablation.  
A patient will have a lesion (“target lesion”) that meets the inclusion criteria upon entering 
the study. If a patient has more than one lesion, only one lesion may be treated during 
the ablation procedure (Visit 2A). If new non-target lesions meet the inclusion criteria, 
they may be treated. However, only one lesion (“target or new”) that meets the inclusion 
criteria may be ablated at any one time during the follow-up period of 12 months. 
 
Microwave Ablation Procedure 
Microwave ablation is a minimally invasive procedure that uses electromagnetic waves 
to generate tissue necrosis, which in this study, is in the lung.  
Antibiotics must be administered prior to each ablation procedure. All ablations will be 
performed under general anesthesia via transbronchial approach by an interventional 
pulmonologist or thoracic surgeon. It is recommended that an interventional radiologist 
(IR) be present at all ablations.  
For those patients who specifically consent, the procedure may be filmed for training and 
research purposes (only applicable to selected patients). 
CP-EBUS will be performed immediately prior to the ablation procedure to establish stage 
certainty and confirm that the lung disease has not spread to other parts of the body, such 
as to the lymph nodes. A biopsy of the lung lesion may be done per the study site’s SOC; 
however, it may not be done at the same time as the CP-EBUS and the ablation 
procedure.  
The size of the lesion will be measured and recorded on the day of ablation (Visit 2A). 
Afterwards, cone beam CT will be used to guide the microwave ablation probe to the 
target soft tissue lesion.  
Cone beam CT scans will be used at three timepoints during the ablation process: 
(1) Pre-ablation: Just prior to inserting the probe into the soft tissue lesion, CT will be 
used to confirm soft tissue lesion details; (2) Intra-ablation: Immediately before the 
ablation, after the intrabronchial sheath has been retracted, cone beam CT scans will be 
used to confirm that the probe is in the intended location and, if not, repositioned and 
another scan will be taken. The physician will repeat this process, until the intended 
position is achieved and a scan taken; and, (3) Post-ablation. After completing the 
ablation, cone beam CT scans will be used to confirm that the ablation margins are 
adequate. If they are not adequate, the ablation application (with scans) should be 
repeated, if possible.  
The smallest distance in the ablation zone, as well as the distance from the edge of the 
ablation zone to the edge of the target lesion (i.e., the treatment margin), must be 

 
 
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measured and captured in the clinical database. 
The Investigator will submit at least three cone beam CT scans for the day of each 
ablation to the central radiologist, as per the Central Radiology Review Manual. All cone 
beam CT scans (taken during the ablation procedure) and all conventional CT scans 
(taken during the post-ablation follow-up visits) should be sent in DICOM format, where 
possible, for central radiology review, via the Imaging Core Lab Services, LLC (ICLS) web 
portal. The central radiologist will produce multiplanar, volumetric, three-dimensional (3-
D) images to independently assess the outcome of the ablation. 
If PET scan is taken during the follow-up period, the site must also perform the diagnostic 
CT as per protocol. The central radiologist will independently review all CT scans taken 
at Screening and throughout the clinical study to reduce the variability between 
investigators in assessing scans and to minimize potential bias. The central radiologist’s 
assessment will be used only for statistical analysis, while the Investigator’s assessment 
will be used for the treatment of the patients in the study. Any discordance between 
Investigator’s assessment and the central radiologist’s assessment will be reported. 
The Sponsor will receive the full CT image sets of all patients. These image sets will be 
used to further the development of the NEUWAVE Flex Microwave Ablation System 
software. The software development will focus on increasing the ability to target the 
lesion, ensure accurate probe placement, and confirm ablation margins. Data will be held 
until development of the software is completed.  
The treatment goal is to achieve a successful ablation, which is determined by meeting 
two endpoints: (1) technical success, which means that the ablation zone completely 
overlaps or encompasses the target lesion plus an adequate ablative margin, as defined 
by the treating physician, and as assessed by cone beam CT imaging; and, (2) technique 
efficacy, which means that no lesion progression is visible on CT scan 30 days ± 7 days 
after the first ablation procedure.  
The Sponsor will provide a Product Development Specialist at every ablation to 
troubleshoot any technical issues with the NEUWAVE Flex Microwave Ablation System. 
Additionally, the Sponsor will also provide a medical specialist experienced in this 
procedure for the treating physician to consult at each ablation. The Sponsor will also 
provide a basic guide for performing a transbronchial microwave ablation with the flexible 
probe using the NEUWAVE Flex Microwave Ablation System. 
The ablation will be performed using the NEUWAVE Flex Microwave Ablation System, 
per the device’s Instructions for Use (IFU) and the performing physician’s clinical 
judgment.  
Post treatment follow-up will be carried out as per Table 1: Schedule of Assessments (at 
the end of the synopsis). 
Electromagnetic waves are delivered to the tissue, producing frictional heating to 
generate tissue necrosis at > 60°C. Duration of treatment and power application will be 
determined by the performing physician based on manufacturer guidelines, with 
adjustment for soft tissue lesion size, proximity to vulnerable structures, and real-time 
intraprocedural monitoring, as needed. Ablation outcome will be classified as: 
• 
Complete ablation (Technical success): defined as ablation of the target lesion 
according to the protocol and covered completely, with an adequate margin, as 
defined by the performing physician (that is, the ablation zone completely overlaps 
or encompasses the target lesion plus an ablative margin), as assessed by cone 
beam CT imaging, immediately following the procedure. 

 
 
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• 
Incomplete ablation: defined as ablation of the target lesions according to the 
protocol but not covered completely with an adequate margin as defined by the 
performing physician (i.e., ablation zone does not overlap or encompass the target 
lesion plus an ablative margin), as assessed by cone beam CT imaging, 
immediately following the procedure.  
Total Radiation Exposure 
The total radiation exposure for each patient will be dependent on the number of CTs per 
patient and the type of CTs, as well as many other factors, such as the manufacturer of 
the scanning equipment. Conventional CT has an average radiation range 0.1 mSv to 
15 uSv,6 while the average radiation range for cone beam CT is considerably higher: 
19 uSv to 1073 uSv.7 The total radiation exposure to the patient during the ablation 
procedure will be captured. 
 
8.1.1 System Overview(s) 
The NEUWAVE Flex Microwave Ablation System is a fully featured soft tissue ablation 
system that uses small diameter flexible ablation probes, a single high-powered, 
gas-cooled microwave source operating at 2.45 GHz, a CO2-based cooling system, a 
Power Distribution Module (PDM), and a support arm designed to hold the PDM in a 
user-selected position. Microwave energy is applied to the target tissue via a single 
flexible ablation probe, heating the tissue to the point of necrosis.  
The NEUWAVE Flex Microwave Ablation System is designed to be used in target 
ablation. Target ablation involves placing a probe into a substantial target and then 
ablating for up to several minutes until the target tissue is necrotic. The NEUWAVE Flex 
Microwave Ablation System is designed for ablations in soft tissue in percutaneous (via 
an introducer) procedures, open surgical procedures, and procedures in which the target 
tissue is accessed via a lumen or scope such as an endoscope or laparoscopic port. 
Two microwave ablation probes are available for use with the NEUWAVE Flex Microwave 
Ablation System: the FLEX4 and the FLEX6. They are comprised of a conical tip on the 
end of a flexible cable and a connector assembly. The probe with the sharper tip (FLEX6) 
is designed for easier tissue penetration while the probe with the less sharp tip (FLEX4) 
is designed for improved navigation. Both FLEX probe models are French gauge 6 (outer 
diameter of less than 2 mm) and 150 cm long. Both probe models have the same antenna 
design and ablation performance characteristics. 
Each probe contains three temperature measurement sensors that help monitor 
performance and ensure patient and operator safety. 
The FLEX probe antenna was designed to produce an ablation zone substantially 
equivalent to the predicate Certus PR probe, but within a flexible probe shaft. Like the 
predicate Certus PR probe, the FLEX probes are designed to produce ablations that 
encompass the tip of the probe while limiting the overall length of the ablation. Testing in 
ex-vivo liver, lung, and kidney tissue confirm that the FLEX probes produce ablations that 
are substantially equivalent to the predicate probes. 
The PDM and Accessories Support Arm (“The Arm”) holds the PDM in a user-selected 
position. The Arm attaches to an imaging/procedure table via a rail mount. This allows 
the PDM and probe to move with the patient, greatly reducing the potential for patient 
injury due to accidental probe movement.  
The Arm is comprised of three jointed lengths with two tension knobs that allow the user 

 
 
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to maneuver and fix the Arm at the user-selected position. The PDM mount on the ARM 
has a dovetail design with magnetic retention for quick and easy mounting. Additionally, 
the Arm has a grasping mechanism that can be used to hold a scope, such as an 
endoscope (if used) in a fixed position for an extended period.  
A CO2 based cooling system ensures the non-active portion of the probe does not exceed 
temperature requirements. 
The system uses two customer-supplied E-sized CO2 cylinders. The system monitors the 
pressure of the tanks and heats the tanks to maintain the desired tank pressure. The 
FLEX System will select which cylinder to initially use based upon tank pressures. 
 
8.1.2 Identity of Study Products 
For this study, medical devices will be used in accordance with manufacturer design 
specifications, product instructions, and guidelines. 
 
TEST PRODUCT: NEUWAVE FLEX MICROWAVE ABLATION SYSTEM AND 
ACCESSORIES  
Product 
Code 
Description 
NWF1US1N NEUWAVE Flex Microwave Ablation System, 120 Vac DR-000770 
FLEX6 
NEUWAVE Microwave Ablation Probe, 6 French, 150cm DR-000899 
FLEX4 
NEUWAVE Microwave Ablation Probe, 6-French, 150cm DR-000900 
ARM1 
The Arm Endoscopic Support Arm, DR-000674 
ARM2 
The Arm Endoscopic Support Arm, Dovetail Mount, DR-000980 
 
8.1.3 Investigational/Study Product Accountability 
The NEUWAVE Flex Microwave Ablation System and the microwave ablation probes 
(FLEX4 and FLEX6) must be stored in conditions according to product labeling and IFU. 
It is the responsibility of the Principal Investigator to ensure that devices are stored 
correctly at the site. 
The Principal Investigator or responsible person designated by the Principal Investigator 
must account for all study devices throughout and, at the end of, the clinical study. During 
the course of the study, the study’s ablation probes must be stored in a locked or secure 
access location. An inventory record must be maintained of all devices received, used or 
returned during the clinical trial. The Principal Investigator must allow the Study Monitor 
access to the secured facility where the study devices are stored to check inventory.  
The Sponsor will supply the NEUWAVE Flex Microwave Ablation System and the 
microwave ablation probes to the study sites. Upon receipt, the Investigator will do the 
following: 
• Conduct an inventory. 

 
 
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• Upon confirmation that all materials arrived intact, complete the Packing List for 
Clinical Supplies included with the shipment. The Sponsor should be contacted 
immediately if any materials are damaged or missing from the shipment. 
• Sign and date the packing list, and promptly return it to the Sponsor. 
• Retain a copy of the signed and dated Packing List for Clinical Supplies for the 
Investigator’s records. 
 
The study device inventory must be available for periodic inspection/verification. 
 
8.2 Visits 
Table 1: Schedule of Assessments may be found at the end of Section 1.0 Synopsis. 
8.2.1 Visit 1 – Screening 
The screening assessments for this visit may occur over several dates within 30 days prior 
to Visit 2. 
Patients will be selected for microwave ablation based on the pre-procedure 
investigations and the Investigator’s interpretation of the clinical picture. Eligible patients 
will be provided with the study information, including the ICF. 
The following screening assessments will occur prior to the study procedure: 
• 
Patients must be given ample time to review and sign the ICF. 
• 
Collect demographic information (age at time of Visit 1, sex, race, ethnicity). 
• 
Review and collect medical and surgical history, including date of diagnosis of soft 
tissue lesion under study, radiation history, and smoking status. 
• 
Collect height and body weight for BMI 
• 
Evaluate ECOG performance status. 
• 
Record the American Society of Anesthesiologists (ASA) score, which is a global 
score that assesses the physical status of patients before surgery. 
• 
Record all prior medications taken within 30 days of Visit 2 and all current 
medications, including but not limited to chemotherapy, steroids, anti-
inflammatories, NSAIDs, hormonal therapy, homeopathic/natural medications, 
nutritional supplements, and antibiotics.  
• 
Review inclusion/exclusion criteria and determine if the patient is eligible to 
participate in the study.  
• 
QOL questionnaires European Organization for Research and Treatment of 
Cancer (EORTC) QLQ-C30 and the lung-specific QLQ-LC13. The questionnaires 
may be administered over the phone, as needed. 
• 
Numeric Pain Rating Scale. 
• 
CT scan of the lung to determine soft tissue lesion details (e.g., size, lesion type, 
location, shape).  
• 
Using the ICLS web portal, send the scan to the central radiologist for independent 
review (refer to the Central Radiology Review manual).  
• 
Obtain PFTs, which may include spirometry, diffusion capacity (also called the 
DLCO [diffusing capacity of the lung for carbon monoxide]), lung volume tests, 
pulse oximetry, and FeNO tests. 
• 
Laboratory tests. If the following tests (based on the study site’s SOC) will be 
completed within 30 days of Visit 2, then they do not need to be repeated at the 

 
 
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Screening visit: 
o CBC (with differentials). 
o Coagulation tests (APTT, INR, PT, PTA, PTT). 
o Serum pregnancy test, for women of childbearing potential only. 
o Any genetic markers relevant to the lesion, if done per SOC. 
 
8.2.2 Visit 2 – Ablation Procedure Through Discharge (Visit 2B) 
CP-EBUS is performed immediately prior to the ablation procedure to establish disease 
stage certainty. A biopsy of the lung lesion may be done per the study site’s SOC; 
however, it may not be done at the same time as the CP-EBUS and the ablation 
procedure. 
The Sponsor will provide a Product Development Specialist at every ablation to 
troubleshoot any technical issues with the NEUWAVE Flex Microwave Ablation System 
and Accessories. Additionally, the Sponsor will also provide a medical specialist 
experienced in this procedure for the treating physician to consult at each ablation. 
On the day of ablation, cone beam CT scans will be done at the timepoints listed in the 
section below.  
Visit 2A: Intraoperative (Ablation) 
Data collected before and during the procedure: 
• 
Administer antibiotics prior to the ablation procedure. 
• 
Use CP-EBUS immediately prior to ablation to confirm disease stage. 
• 
Measure and record the size of the lesion to confirm inclusion criteria (lesion must 
be ≤ 2 cm). 
• 
Prior to ablation, confirm that the patient still meets inclusion and exclusion criteria 
(tests not needed to be repeated). 
• 
Collect height and body weight for BMI, and evaluate ECOG performance status 
(prior to ablation). 
• 
Record all concomitant medications, including but not limited to chemotherapy, 
steroids, anti-inflammatories, NSAIDs, hormonal therapy, homeopathic /natural 
medications, nutritional supplements, and antibiotics. Do not record components 
of the anesthesia medications used for the ablation procedure. 
• 
Record all concomitant procedures. 
• 
QOL questionnaires EORTC QLQ-C30 and the lung-specific QLQ-LC13 (prior to 
ablation). The questionnaires may be administered over the phone, as needed. 
• 
Numeric Pain Rating Scale (prior to ablation). 
• 
Cone beam CT scans of the lung:  
- 
Pre-ablation: to confirm soft tissue lesion ablations details (type of cell, size, 
and location). 
- 
Intra-ablation:  
o Step 1: to guide the probe to the soft tissue lesion. 
o Step 2: to ascertain the location of the probe after the intrabronchial 
sheath has been retracted (more than one scan may be needed; only 
the last scan needs to be submitted for central review). 

 
 
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- 
Post-ablation: to confirm the ablation is complete with an adequate margin. 
• 
Using the ICLS web portal, send the scans to the central radiologist for independent 
review (refer to the Central Radiology Review manual). 
• 
Record ablation procedure details, including but not limited to: 
o Date and time of the ablation procedure. 
o Anatomical location of ablations. 
o Number of ablation cycles and power used for each ablation. 
o Number of cone beam CT scans performed for probe placement and 
margin assessment. 
o Number of probe placement attempts per ablation. 
o Duration of procedure, measured as the time when the bronchoscope 
enters the endotracheal tube to the time when the last cone beam CT 
scan is taken. 
 
Note: Some of the above ablation procedure details will be provided to the site 
via a report generated from the Call Home Database. The study site will review 
the report and enter the procedure details into the clinical database, as 
applicable. 
• User Experience Survey answered by the treating physician post-ablation 
(available as a separate document). 
• Evaluate technical success, defined as ablation of the target lesion according to 
the protocol and covered completely, with an adequate margin, as defined by 
the performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus an ablative margin). Technical success is 
assessed by cone beam CT imaging, immediately following the ablation 
procedure. 
• Radiation exposure from the CT scans. 
• Record any AEs/SAEs that occur from the start of the ablation.  
 
Visit 2B: Discharge  
After the ablation procedure, the patient will be observed for up to 23 hours and 
afterwards discharged from the study site (except in cases where the Investigator 
deems it is necessary for the patient to remain hospitalized). During that 23-hour 
period, the following assessments will occur:  
• Record all concomitant medications.  
• Record all concomitant procedures. 
• QOL questionnaires EORTC QLQ-C30 and the lung-specific QLQ-LC13. The 
questionnaires may be administered over the phone, as needed. 
• Numeric Pain Rating Scale. 
• Length of hospital stay, measured from post-ablation to discharge. 

 
 
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• All AEs/SAEs. 
• De-identified UB-04 data, if allowed, to be provided to the Sponsor by the site. 
 
8.2.3 Visit 3 – 30-day Follow-up 
One month (approximately 30 days ± 7 days) after the ablation procedure, the patient will 
visit the study site and the following assessments will occur: 
• Record all concomitant medications. 
• All concomitant procedures. 
• QOL questionnaires EORTC QLQ-C30 and the lung-specific QLQ-LC13. The 
questionnaires may be administered over the phone, as needed. 
• Numeric Pain Rating Scale. 
• Collect height and body weight for BMI, and evaluate ECOG performance 
status. 
• CT scan to determine soft tissue lesion details (e.g., size, lesion type, location, 
shape). Using the ICLS web portal, send the scan in DICOM format, where 
possible, to the central radiologist for independent review (refer to the Central 
Radiology Review manual). If PET scan is taken during follow-up, the site must 
also perform the diagnostic CT. 
• Laboratory tests, as follows:  
o CBC (with differentials). 
o Coagulation tests (APTT, INR, PT, PTA, PTT). 
• Technique efficacy, defined as ablation of the target lesion according to the 
protocol and covered completely, with an adequate margin, as defined by the 
performing physician (that is, the ablation zone completely overlaps or 
encompasses the target lesion plus an ablative margin). Technique efficacy is 
assessed using CT imaging at Visit 3. Record the number of successful repeat 
ablations of the target lesion, if applicable. 
• Record readmission to any hospital for any reason within 30 days of the ablation. 
The Investigator will assess the reason for the admission and capture the reason 
in the clinical database. 
• All AEs/SAEs. 
 
8.2.4 Visit 4 – 6-month Follow-up 
Visit 4 occurs 6 months (± 1 month) after the first ablation procedure (Visit 2A). The patient 
must visit the study site for the following assessments: 
• Record all concomitant medications. 
• All concomitant procedures. 
• QOL questionnaires EORTC QLQ-C30 and the lung-specific QLQ-LC13. The 
questionnaires may be administered over the phone, as needed. 

 
 
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• Collect height and body weight for BMI, and evaluate ECOG performance 
status. 
• CT scan to determine soft tissue lesion details (e.g., size, lesion type, location, 
shape). Using the ICLS web portal send the scan in DICOM format, where 
possible, to the central radiologist for independent review (refer to the Central 
Radiology Review manual). If PET scan is taken during follow-up, the site must 
also perform the diagnostic CT. 
• Obtain PFTs (spirometry, diffusion capacity (DLCO), lung volume tests, 
6-minute walk or pulse oximetry, and FeNO tests). 
• Laboratory tests, as follows:  
a. Complete blood count (CBC; with differentials). 
b. Coagulation tests (APTT, INR, PT, PTA, PTT). 
• Record the number of successful repeat ablations, if applicable. 
• All AEs/SAEs. 
 
8.2.5 Visit 5 – 12-month Follow-up / End-of-Study 
Approximately 12 months (± 1 month) after the first ablation procedure is Visit 5, the 
end-of-study visit. At this final visit of the study, the patient will visit the study site where 
the following assessments will occur: 
• Record all concomitant medications. 
• All concomitant procedures. 
• QOL questionnaire (EORTC QLQ-C30) and the lung-specific QLQ-LC13. The 
questionnaires may be administered over the phone, as needed. 
• Collect height and body weight for BMI, and evaluate ECOG performance 
status. 
• CT scan of the lung to determine soft tissue lesion details (e.g., size, lesion type, 
location, shape). Using the ICLS web portal, send the scan in DICOM format, 
where possible, to the central radiologist for independent review (refer to the 
Central Radiology Review manual). If PET scan is taken during follow-up, the 
site must also perform the diagnostic CT as per protocol. 
• Obtain PFTs (spirometry, diffusion capacity (DLCO), lung volume tests, 
6-minute walk or pulse oximetry, and FeNO tests). 
• Laboratory tests, as follows:  
a. Complete blood count (CBC with differentials). 
b. Coagulation tests (APTT, INR, PT, PTA, PTT). 
• Record the number of successful repeat ablations, if applicable. 
• All AEs/SAEs. 
• Record date of study completion. 
 

 
 
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8.2.6 Unscheduled Visits 
The following data will be collected during each unscheduled visit: 
• Reason for the unscheduled visit. 
• AEs/SAEs, if applicable. 
• Any update to concomitant medications and procedures. 
 

 
 
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9.0 DATA MANAGEMENT AND INTEGRITY 
9.1 Data Completion and Record Keeping 
Source Documents 
Source documents are documents on which information regarding patients is first 
recorded, including printed, optical, or electronic documents. Investigator patient files or 
hospital records generally are the basis of source document information. This includes, 
but is not limited to, the following: original patient files; hospital/clinic records; original 
recordings/tracing; digital images from automated instruments (e.g., cameras); 
radiographs; device accountability records; photographic negatives; and, records kept at 
the investigation site, at the laboratories, and at other departments involved in the clinical 
investigation. 
Another source of source documents is data from NeuWave Medical’s Call Home 
Database. NEUWAVE Ablation System has a functionality that electronically collects 
procedure data and information during the ablation procedure and is transmitted by the 
NEUWAVE Ablation System to NeuWave Medical, Inc., after the conclusion of each 
ablation procedure; this information is collectively called the “Call Home Database.” The 
procedure data include, but are not limited to, the following: date and time of procedure, 
anatomical location of ablations, number of ablation cycles and power used for each 
ablation, guidance method used, number of distinct cone beam CT scans performed for 
probe placement and margin assessment, number of probe placement attempts per 
ablation, type of probes used, type of anesthesia, duration of procedure (measured as 
the time when bronchoscope enters the endotracheal tube to the time when the last cone 
beam CT scan is taken) and radiation exposure from CT scans. Some of these relevant 
ablation procedure details will be provided to the site via a report generated from Call 
Home Database. The study site will review the report for accuracy and enter the 
procedure details into the study’s clinical database. Reports generated from the Call 
Home Database must be retained by the Investigator as part of the patient’s permanent 
medical record. The report should be retained for review and source data verification by 
the monitor.  
All cone beam CT scans (taken during the ablation procedure) and all conventional CT 
scans (taken during the post-ablation follow-up visits) should be sent in DICOM format 
(where possible) for central radiology review, via the ICLS web portal.  
The Sponsor will also receive the full CT image sets of all patients. These image sets will 
be used to further the development of the NEUWAVE Flex Microwave Ablation System 
software. The software development will focus on increasing the ability to target the 
lesion, ensure accurate probe placement, and confirm ablation margins. Data will be held 
until development of the software is completed. 
Only for those patients who specifically consent, some of the treatment data and outcome 
data that is already being captured for this study will also be compiled with the same type 
of data from consenting patients from other NeuWave Medical studies. These data will 
be collectively used for Microwave Time and Power predictive analytics and reported in 
an aggregate fashion.  
Also, only for those patients who specifically consent, some ablation procedures will be 
filmed for training and educational purposes. 
Source documents must be retained by the Investigator as part of the patient’s permanent 
medical record. The information in the source documents is used to complete the eCRFs. 

 
 
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All information captured on the eCRFs should be completely and accurately supported in 
source documentation. Any additional information relevant to the study should be 
included in the source documents. Particularly, any deviations from the protocol or 
procedures should be recorded in the source documents. The Investigator will retain 
originals of all source documents, patient consent forms, and study data. 
Electronic Data Capture 
An EDC system will be used by site personnel to transfer data from source records 
(medical records and/or source document worksheets) onto common eCRFs. This 
system is a web-based, secure electronic software application (Medidata Rave, 350 
Hudson Street, 9th Floor, New York, NY 10014 United States; telephone: 212-918-1800; 
Fax: 212-918- 1818; toll-free: 877-511-4200). This system was designed and is 
developed and maintained by Medidata, Inc. in a manner that is compliant with national 
and international GCP data protection/data privacy and electronic record/electronic 
signature (e.g., 21 CFR Part 11) regulatory requirements. The EDC system will be used 
to facilitate the collection of all data at the site. Designated site personnel will be 
responsible for entering patient data into the EDC system. All external and Sponsor 
internal users will be trained on the EDC application at a level dependent on their planned 
function. An EDC digital User Manual will be available under the help menu within the 
Medidata Rave website to assist in the collection and entry of source data into the 
electronic casebook.  
A 24/7/365 Help Desk Support line (telephone: 973-659-6780; fax: 973-954-5621; toll 
free: 866-633-4328; Email: helpdesk@mdsol.com) staffed by the outsourced vendor will 
also be available to respond to site and monitor questions. 
Data Collection 
Each EDC eCRF will be completed by the Principal Investigator (PI) or PI’s designee. 
Every effort should be made to respond to all monitoring and/or data management 
questions on each eCRF as completion of the data is required by the protocol. A unique 
ID number will identify each patient. The patient’s unique study ID number will be visible 
on each eCRF. At no time, should the patient name appear on the eCRFs.  
All data should be recorded accurately and completely. The Investigator is responsible 
for reviewing and approving each completed eCRF. The Investigator will document 
assurance of overall review and approval by electronically signing each patient’s 
electronic casebook. 
Data Correction 
Required data corrections to eCRFs will be prompted via automated electronic edit 
checks and/or queries manually created by Sponsor reviewers. The change, the person 
making the change, and the time the change was made to the eCRFs will be automatically 
captured in the audit trail within Medidata Rave. 
Data Privacy 
The collection, use, and disclosure of all personal data, including patient health and 
medical information, are to be maintained in compliance with applicable personal data 
protection and security laws and regulations that govern protected health information and 
the informed consent given by each patient. When collecting and processing such 
personal data, appropriate measures are to be taken to maintain the confidentiality of 
patient health and medical information and to prevent access by unauthorized persons. 

 
 
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None of the data collected and transmitted by Call Home Database is attributable to an 
identifiable patient. 
Record Retention, Inspection, and Custody 
The Investigator must maintain all documentation related to the study until notified by the 
Sponsor. The Investigator will allow representatives of the Sponsor, the FDA, or other 
government regulatory agencies to inspect all study records, eCRFs, and corresponding 
portions of the patient’s office and/or hospital medical records at regular intervals during 
the study. These inspections are to verify adherence to the protocol, integrity of the data 
being captured on the eCRFs, and compliance with applicable regulations. 
Study reports will not identify patients by name. These reports may be submitted to the 
FDA and/or regulatory authorities.  
If custody of the clinical study records is transferred, notice of such a transfer should be 
given to the Sponsor no later than 10 working days after the transfer occurs. 
9.2 Medical Dictionary Coding 
Medical dictionary coding of medical history and verbatim AEs captured on eCRFs will be 
performed using a coding thesaurus algorithm. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used after data entry and query resolution, via auto-encoding 
and interactive coding processes. 
9.3 Data Quality Assurance 
A protocol deviation is any noncompliance with the study protocol, Good Clinical Practice, 
or protocol-specific requirements. A deviation (any activity conducted outside the 
parameters established by the study protocol) can be identif ied from a number of sources. 
Potential sources include, but are not limited to: a member of the Investigator’s staff, a 
Sponsor representative during monitoring visits, or a member of the data management or 
statistical groups when entering or analyzing data. Regardless of the source, it is crucial 
to document the deviation in the protocol deviation eCRF. The Investigator will report 
protocol deviations to the IRB as required by the IRB procedures. 
Steps to be taken to assure the accuracy and reliability of  data include the selection of 
qualified investigators and appropriate sites, review of protocol procedures with the 
Investigator and associated personnel prior to the study, and periodic monitoring visits by 
the Sponsor. The Sponsor will review eCRFs for accuracy and completeness during on-
site monitoring visits; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 
Any deviations from the protocol or procedures should be recorded in the source 
documents. 
All protocol amendments must be issued by the Sponsor, signed and dated by the 
Investigator, and should not be implemented without prior IRB approval, except where 
necessary to eliminate immediate hazards to the subjects or when the change(s) involve 
only logistical or administrative aspects of the study, e.g., change in monitor(s), change 
of telephone number(s). The Investigator reports the protocol amendments to the IRB/EC 
as per their local requirements. 
Investigator Training 
Prior to screening patients for this study, the PI, sub-Investigators, study coordinators, 
and other designated staff (as applicable) will be provided information on study execution, 

 
 
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data collection, and procedures specific to this clinical protocol. 
Monitoring 
This study will be monitored by the Sponsor to ensure the following: 
• 
The rights and well-being of the patients are protected. 
• 
The reported data is accurate, complete, and verifiable from source documents 
where utilized. 
• 
The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), applicable GCPs, and with applicable local/regional 
regulatory requirements. 
 
The extent and nature of monitoring will be predetermined and agreed to by the Sponsor 
and investigators. Monitors will comply with established written standard operating 
procedures as well as procedures (i.e., monitoring plan) specified by the Sponsor for 
monitoring this study as characterized in the monitoring plan. 
9.4 Protocol Deviations 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate sites, the review of protocol procedures with the 
Investigator and associated personnel prior to the study, and periodic monitoring visits by 
the Sponsor. The Sponsor will review eCRFs for accuracy and completeness during on-
site monitoring visits; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 
 
 
10.0 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND 
DETERMINATION OF SAMPLE SIZE 
10.1 
Statistical and Analytical Plans 
The Sponsor Data Management and Biostatistics groups will be responsible for the 
analysis of data from this protocol. A comprehensive and detailed Statistical Analysis Plan 
will be finalized prior to database lock to supplement the statistical design and analysis 
described in this section. 
Categorical variables will be summarized descriptively by frequencies and associated 
percentages. Continuous variables will be summarized descriptively by number of 
patients, mean, standard deviation, median, minimum, and maximum.  
10.2 
Study Design 
This is a multicenter, single-arm study. 
10.3 
Treatment Assignment 
This is a single-arm study where all enrolled patients will receive the same treatment: 
microwave ablation performed with the flexible probe using the NEUWAVE Flex 
Microwave Ablation System and Accessories. There will be no blinding or randomization. 

 
 
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10.4 
Interval Windows 
Interval windows are provided in Table 1: Schedule of Assessments. No additional 
windows are planned for analysis purposes. 
10.5 
Primary Endpoints 
The primary objective of this study is to evaluate the NEUWAVE Flex Microwave Ablation 
System and Accessories in transbronchial ablation procedures for adult patients with 
medically inoperable primary soft tissue lesion that are ≤ 2 cm, located in the outer two-
thirds of the lung and not closer than 1 cm to the pleura, at Visit 3, which is 30 days 
± 7 days after the first ablation procedure, based on the following: 
a) Device user experience 
b) Technical success 
c) Technique efficacy. 
The data for the evaluation of device user experience will come from the User Experience 
Survey, which will be completed by the treating physician following each ablation 
procedure throughout the study, when applicable. 
Primary endpoints for technical success and technique efficacy are defined in Section 
6.0, above.  
The study will be descriptive in nature and thus no hypotheses for any of the primary 
endpoints are specified levels of significance. 
10.6 
Levels of Significance 
No levels of significance are specified because no hypotheses are planned to be tested. 
10.7 
Analysis Sets 
The primary analysis of safety and effectiveness endpoints will be performed on the Full 
Analysis Set, defined as all patients who are enrolled in the study and receive ablation 
through the flexible probe. A Per Protocol analysis set will be defined as all patients who 
had undergone the ablation procedure and have no major protocol deviations. 
Effectiveness analyses will be repeated for the Per Protocol Set. 
10.8 
Sample Size Justification 
No formal hypotheses are being tested in this study and hence a target sample size of 
40 patients (with an approximate equal distribution of device use by interventional 
pulmonologists and thoracic surgeons) is deemed adequate for a preliminary 
investigation of the feasibility of this procedure, as well as for providing sufficient 
information for appropriately sizing a subsequent study. 
From a safety perspective, the AEs of interest in this study include: pneumothorax 
(requiring tube drainage), hemorrhage (bleeding requiring medical intervention), 
post-ablation syndrome, pain, pleural effusion (requiring tube drainage), infection, 
pneumonia, abscess, and bronchopleural fistula. A target sample size of 40 patients 
provides a high likelihood of observing events in this composite and will allow for an initial 
evaluation of the frequency of occurrence relative to published literature in similar 
procedures. 

 
 
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10.9 
Analyses to be Conducted 
Analyses described below will be performed on the pooled set of 40 patients, as well as 
summarized separately for the set of patients treated by interventional pulmonologists 
and by thoracic surgeons. No comparisons between these groups are planned. In the 
event that these groups enroll at different rates, subgroup analyses for the first group that 
is completely enrolled may be performed to support publication purposes prior to the 
overall summary on all 40 patients, and subsequent subgroup summary of the slower 
enrolling user group.  
Disposition of Study Patients 
Patient disposition will be summarized using counts and percentages. The number and 
percentage of patients completed and discontinued along with the specific reasons for 
discontinuation will be tabulated by treatment group and in total. 
Demographic and Baseline Characteristics 
Summary statistics will be provided for patient demographics and pre-operative ablation 
characteristics.  
Primary and Secondary Endpoint Analyses 
Device user experience feedback will be collected from the treating physician who will 
complete the User Experience Survey following each ablation procedure. The 
questionnaire will focus on procedure workflow and the user’s assessment on 
ease/difficulty of using the device. Summary statistics will be provided for each question. 
The number and percentage of patients achieving technical success will be summarized 
and a 95% confidence interval will be estimated. Technique efficacy, as well as primary 
and secondary efficacy rates and hospital readmission rates, will be summarized in a 
similar manner. Local soft tissue lesion recurrence rates will be estimated using the 
Kaplan-Meier method and 95% confidence intervals will be provided. 
The number and percentage of patients experiencing AEs from the start of ablation (Visit 
2A) to Visit 3 (the first post-ablation visit) will be summarized by MedDRA preferred term 
and system organ class. A similar summary will also be provided for device related and 
procedure related, and all SAEs. Ninety-five percent confidence intervals may be 
provided for pre-specified adverse events of interest, which are:  
1. 
pneumothorax (requiring tube drainage)  
2. 
hemorrhage, bleeding requiring medical intervention  
3. 
post-ablation syndrome  
4. 
pain  
5. 
pleural effusion, requiring tube drainage  
6. 
pneumonia  
7. 
abscess  
8. 
infection  
9. 
bronchopleural fistula.  
Similar summaries will also be provided for the entire observation period from the ablation 
procedure date through 1 year of follow-up.  

 
 
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The EORTC QOL questionnaires and Numeric Pain Rating Scale scores will be 
summarized with methodology consistent to the recommendations of the specific survey. 
Additional endpoints will be summarized with descriptive statistics.  
Plans for Interim Analysis 
There are no plans for interim analyses, whose intent would be to stop the study early or 
to modify the study design. Two analysis timepoints are planned. The first analysis will 
occur after all patients within a treatment group (interventional pulmonologist or thoracic 
surgeon) complete Visit 3 (30 days ± 7 days after the first ablation procedure). The 
analysis will provide a summary of the User Experience Survey, technical success, 
technique efficacy, and safety through Visit 3. When the second group completes this 
timepoint, results will be summarized for that group and subsequently in total. The second 
analysis timepoint will be at the completion of the study. 
Ongoing Review 
The Sponsor will provide a Product Development Specialist at every ablation to 
troubleshoot any technical issues with the NEUWAVE Flex Microwave Ablation System 
and Accessories. Additionally, the Sponsor will also provide a medical specialist 
experienced in this procedure for the treating physician to consult at each ablation. 
The Sponsor will also review complications periodically, as per the Safety Management 
Plan. Complications that may occur during and after microwave lung ablations may 
include, but are not limited to, the following:  
• 
pneumothorax (requiring tube drainage)  
• 
hemorrhage, bleeding requiring medical intervention  
• 
post-ablation syndrome  
• 
pain  
• 
pleural effusion (requiring tube drainage)  
• 
pneumonia  
• 
abscess  
• 
infection  
• 
bronchopleural fistula.  
A report of death will stop enrollment and require an investigation to determine if the death 
is related to the ablation procedure. If the death is deemed not related to the ablation 
procedure the study may resume enrollment. 
Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB) will be appointed by the Sponsor to review, on 
a regular basis, safety data from the study. The DSMB will advise the Sponsor regarding 
the continuing safety of patients and those yet to be recruited to the study. Based on 
accumulating data from the study, the DSMB may recommend whether to continue, 
suspend, modify, or stop the study. 
At the conclusion of the review of all 40 patients, the DSMB will also give a final 
assessment of the safety of the procedure. The composition, responsibilities, frequency 
of DSMB meetings, handling of emergency situations, and documentation of DSMB 
meetings is specified in the DSMB Charter. 
 

 
 
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Analysis of Safety 
The analysis of safety is summarized above under Primary and Secondary Endpoint 
Analyses.  
Handling of Dropouts or Missing Data 
All analyses will be performed only on patients undergoing ablation with the flexible probe 
and only observed data will be analyzed. There will be no imputation of missing data for 
any parameters or for early terminated patients. 
Multicenter Studies 
No adjustment for center is planned in the statistical analysis. However, center specific 
analyses may be conducted pending within-center sample size to understand the effect 
that surgeon techniques and site’s SOC may have on the overall results.  
Analysis of Subgroups 
This study will include two groups: 20 patients treated by interventional pulmonologists and 
20 patients treated by thoracic surgeons. All analyses described above will be performed on 
the pooled set of 40 patients, as well as summarized separately for the set of patients treated 
by interventional pulmonologists and by thoracic surgeons. There are no plans to perform 
direct comparisons between the two groups on any outcomes.  
Integrated Multistudy Analysis of Time/Power Data 
“Time and Power” data from this study (i.e., how much time and microwave power was 
applied to a specific lesion, etc) and the results of each ablation treatment (i.e., did the 
treatment result in a complete ablation or not, etc) will be combined with Time and Power 
data and ablation outcome data from other studies that use the NEUWAVE Microwave 
Ablation Systems. The goal of this Time and Power predictive analysis is to characterize 
the optimal microwave ablation treatment parameters for specific lesion types, locations, 
and conditions. All data submitted to and included in this integrated multistudy analysis 
will be de-identified. Nevertheless, each patient will be asked to give consent to allow his 
or her data to be submitted for inclusion in this integrated analysis. There is no additional 
data that will be required for this analysis which is not already collected in this flex probe 
study.  
 
11.0 RISKS AND BENEFITS OF THE STUDY 
This study may or may not provide any benefits to the patient. However, the data collected 
throughout the study may help to assess the efficacy and safety of a new treatment 
technique: transbronchial microwave ablation of soft tissue lesions of the lung. As 
described in the Introduction, retrospective studies of patients who underwent 
percutaneous microwave ablation of the lung as far back as 2003 have provided data that 
the percutaneous route of treatment has been safe and effective. Transbronchial 
microwave ablation of soft tissue lesions represents a new approach that has not been 
routinely used in clinical practice, so there may be some unforeseeable and unknown 
risks associated with this technique in this study.   
 

 
 
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12.0 ADVERSE EVENTS 
12.1 
Definitions 
Adverse Event 
For this study, an adverse event is defined as any undesirable clinical occurrence in a 
patient. All AEs, whether attributable to the device/procedure or not, are to be recorded 
in the eCRF and reported to the Sponsor. 
Expected Morbidity/Anticipated Adverse Events 
An expected morbidity/procedural complication is defined as an AE that is known to be 
common or usual in nature, severity, or incidence during ablation of the lung. 
Serious Adverse Event 
It is the Investigator’s responsibility to determine the “seriousness” of an AE using the 
protocol defined terms below. An SAE is an AE that results in one or more of the following 
for this study: 
• Life-threatening: The patient was at imminent risk of dying at the time of the adverse 
event. 
• Permanent Impairment: An AE that resulted in permanent impairment of a body 
function or permanent damage to a body structure. 
• Necessitated Intervention: An AE that resulted in a condition that necessitated 
medical or surgical intervention to preclude permanent impairment of a body 
function or damage to a body structure. 
• Required in-patient or prolonged hospitalization. 
• A persistent or significant disability or incapacity. 
• Resulted in death: An AE that resulted in the patient’s death 
 
Notes: 
1. Progression of the disease under study should not be reported as an SAE. 
2. “Death” should not be reported as an AE. The cause of death should be reported as 
an SAE. The only exception is “Sudden Death” when the cause is unknown. 
3. Planned hospitalization for a pre-existing condition is not considered an SAE.  
4. A procedure required by the protocol is not considered an SAE, unless the patient 
experiences a serious deterioration in health or hospitalization is prolonged. 
 
The Sponsor will review all reported AEs and SAEs according to the current Safety 
Monitoring Plan. 
Severity of Adverse Events 
It is the Investigator’s responsibility to assess the severity of an AE. A change in severity 
may constitute a new reportable AE. 
The severity of each AE will be determined via the Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0. The CTCAE may be accessed here: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 

 
 
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Also, the following guideline should be used to determine the severity of each AE: 
• MILD: Awareness of signs or symptoms, but does not interfere with the patient’s 
usual activity, or is a transient event that resolves without treatment and with no 
sequelae. 
• MODERATE: A sign or symptom, which interferes with the patient’s usual activity. 
• SEVERE: Incapacity with inability to do work or usual activities. 
 
Relationship of Adverse Events 
It is the Investigator’s responsibility to assess the relationship between all AEs and the 
study procedure.  
The following guidelines should be used in determining the relationship of an AE to a 
device, study procedure, or other causality: 
 
 
Not related 
Temporal sequence between device usage and the event is 
such that the relationship is unlikely. 
Unlikely related 
Temporal sequence between device usage and the event is 
such that the relationship is not unlikely or the subject’s 
condition or concomitant therapy could have caused the AE. 
Possibly related 
Temporal sequence is relevant or the event abates upon 
device usage completion or the event cannot be reasonably 
explained by the patient’s condition. 
Probably related 
Temporal sequence is relevant and the event abates upon 
product device usage or reappearance of the event on repeat 
device usage (re-challenge). 
Causal relationship 
Temporal sequence between device usage and the event is 
such that the relationship is unlikely. 
 
 
12.2 
Reporting Adverse Events  
The Investigator is required to report all AEs experienced by the patient from the start of 
the ablation procedure (Visit 2A) until the patient completes Visit 5 (1 year after the first 
ablation procedure) or withdraws early (prior to Visit 5) to the Sponsor within 14 days of 
become aware of the AEs. All AEs (both serious and non-serious) must be reported in 
the AE eCRF. The Investigator will evaluate the severity of the event and its relatedness 
to the study device or procedure.  
Any necessary medical management of the event will be recorded in the patient’s medical 
record/source document. All AEs must be followed until resolution or until they become 
stable. 
The Investigator will record all AEs (both serious and non-serious) in the source 
documents. CTC (Common Terminology Criteria) should be used when recording AEs. 
In addition, the following information should be recorded: 

 
 
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• Onset date 
• Resolution date or date of death 
• Severity of the event using CTCAE 
• Action taken 
• Event status (ongoing at study end or resolved) 
• Relationship of AE to the ablation device used in the study 
• Relationship of AE to the study procedure 
• Indication of seriousness. 
 
Data related to SAEs will be collected until event resolution, or until the event is 
considered stable, or until all attempts to determine the resolution of the event are 
exhausted. All AEs that are unresolved at study completion (or early termination) will be 
recorded as ongoing at study end. 
 
Reporting Serious and Non-Serious Adverse Events to the Sponsor 
The study site must report all SAEs, whether they are related to the device or procedure, 
to the Sponsor as soon as possible, but no later 72 hours of becoming aware of the SAE. 
The study site will report the SAE by entering the event into the EDC system via the 
Adverse Event eCRF, which will trigger an automated email to the Sponsor. Additional 
information, including the Investigator’s assessment, may be added to the eCRF later; 
however, the study site must complete the AE eCRF within 72 hours of becoming aware 
of the SAE. If the Sponsor requires supporting documentation or other information, the 
Sponsor will contact the study site.  
In the event of death, the Investigator must report all available information to the Sponsor.  
The report of an SAE by a site does not constitute an admission that study personnel or 
the user facility (hospital/clinic) caused or contributed to the event. The study site is 
responsible for submitting AEs to the reviewing IRB/EC, per their IRB/EC procedures. 
Regarding non-serious AEs, the study site is expected to complete the Adverse Event 
eCRF within 14 days of becoming aware of the event. The Investigator must assess 
expectedness, which also will be recorded in the AE eCRF. Supporting documentation 
may be requested, as needed.  

 
 
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13.0 PRODUCT COMPLAINTS 
13.1 
Product Complaint Definition 
A product complaint is defined as any written, electronic, or oral communication that 
alleges deficiencies related to the identity, labeling, quality, durability, reliability, safety, 
effectiveness, or performance of a device after it is released for distribution (21CFR 
820.3 (b)). A product complaint may or may not be associated with an AE/SAE.  
Product complaints may include, but are not limited to: 
1. Product contamination. 
2. Defective components. 
3. Device malfunction (the failure of a device to perform as intended for this study). 
13.2 
Reporting Product Complaints 
All product complaints related to devices in the procedure shall be documented 
throughout the clinical investigation.  
The study site must report product complaints related to a device manufactured by 
NeuWave Medical, Inc., in a timely manner, but no later than 24 hours of becoming aware 
of the event.  
When any representative of the Sponsor becomes aware of a product complaint, the 
Sponsor representative must notify the Sponsor’s Product Complaint Team within 
24 hours of becoming aware of the event.  
The Product Complaint Form must be emailed to the Sponsor Customer Complaint team 
at the following email address: 
Productcomplaint1@its.jnj.com 
The product complaint may also be reported by calling 1-877-ETHICON, Option 5. 
One copy of the processed form should be kept on-site and the device should be retained. 
Sponsor representatives will organize collection of the device for evaluation, as needed. 
 
14.0 PUBLICATION PLAN 
Publication and authorship policies should be determined and aligned with the clinical study 
agreement executed between operating company and each clinical site. Publication of the 
results of this study will be governed by J&J publication policies, including current and 
applicable Medical Device Publication Policy. Any presentation, abstract, or manuscript will be 
made available for review by the Sponsor prior to submission. Licensing agreements or 
copyrights applying to tools, work products or intellectual property used during the study 
should be observed and clearly displayed on study documentation and publications, wherever 
appropriate. 
All manuscripts of data obtained from this clinical study will be reviewed and approved by the 
Sponsor, and each author, prior to any submission. Current and applicable Medical Device 
Publication Policy will be followed. The Sponsor will require a written agreement for any 
external author(s) prior to initiating any publication. All authors must disclose financial or 
personal affiliations that could be considered a conflict of interest.

 
 
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15.0 APPENDICES 
APPENDIX 1: Numeric Pain Rating Scale 
 
The Numeric Pain Rating Scale (NPRS) can be administered verbally (therefore also by 
telephone) or graphically for self-completion. As mentioned above, the respondent is asked to 
indicate the numeric value on the segmented scale that best describes their pain intensity. 
  

 
 
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APPENDIX 2: SPONSOR CONTACT INFORMATION 
 
NEUWAVE MEDICAL, INC. 
Clinical Development & Medical Affairs 
3529 Anderson Street 
Madison WI 53704 
 
MEDICAL LEADER 
Edmund Kassis, MD 
Tel: 713-444-7907 
ekassis@its.jnj.com 
MEDICAL LEADER  
Joseph Amaral, MD 
Tel: 513-337-7722 
jamaral4@its.jnj.com 
CENTRAL 
INDEPENDENT CT 
SCAN REVIEWER 
Christopher Meyer, MD 
University of Wisconsin 
Holly Jackson 
Tel: 608-263-8328 
or Tel: 608-265-4379  
CMeyer2@uwhealth.org 
CLINICAL STUDY 
LEAD 
Bertha Fearon 
Tel: 908-218-2933 
Cell: 908-524-3749 
bfearon1@its.jnj.com 
CLINICAL 
OPERATIONS 
LEAD 
Erin Prifogle Meyers 
Tel: 908-218-2296 
Cell: 937-681-0322 
eprifog1@its.jnj.com 
DATA MANAGER 
Elizabeth Pierce 
Tel: 919-602-1197 
epierce3@its.jnj.com 
 
 
 

 
 
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16.0 REFERENCE LIST 
 
 
1 Ethicon Inc. Target Product Profile. Section 1: Strategic Overview. Sep 2017. 
2 Solazzo SA, Liu Z, Lobo SM, et al. Radiofrequency ablation: importance of background tissue 
electrical conductivity—an agar phantom and computer modeling study. Radiology 2005;236(2):495–
502. 
3 Goldberg SN, Gazelle GS, Compton CC, McLoud TC. Radiofrequency tissue ablation in the rabbit 
lung: efficacy and complications. Acad Radiol 1995;2(9): 776–784. 
4 Ethicon Inc. NeuWave FIHCa Review Deck. 7 Jul 2017. Slide 36. 
5 Ethicon Inc. NeuWave FIHCa Review Deck. 7 Jul 2017. Slide 13. 
6 Brenner DJ and Hall EJ. Computed Tomography — An Increasing Source of Radiation Exposure 
2007.NEJM 3357(22)2277-2284. 
7 Li G. Patient radiation dose and protection from cone-beam computed tomography. Imaging Science 
in Dentistry 2013;43(2):63-69. doi:10.5624/isd.2013.43.2.63.