Pivotal Study of the LUM Imaging System for Assisting Intraoperative Detection of Residual Cancer in the Tumor Bed of Female Patients With Breast Cancer
Phase: PHASE3
Conditions: Breast Cancer
Sponsor: Lumicell, Inc.

LUMICELL CONFIDENTIAL 
This document is confidential. Do not disclose or use except as authorized. 
 
Lumicell Protocol Number: CL0007 
Lumicell Study Identification: CL0007_Breast 
Protocol Version: 08 
Protocol Version Date: 07APR2021 
 
Study Title: PIVOTAL STUDY OF THE LUM IMAGING SYSTEM FOR ASSISTING 
INTRAOPERATIVE DETECTION OF RESIDUAL CANCER IN THE TUMOR BED OF 
FEMALE PATIENTS WITH BREAST CANCER 
 
Funded in part by NIH Grant 5R44CA211013-02 
 
System: LUM Imaging System (LUM015 imaging agent and LUM Imaging Device)  
IDE # G140195/S039 
 
Study Sponsor and Investigational Product 
Supplier: Lumicell, Inc. 
Contact information: 
Jorge Ferrer, Ph.D. 
Senior Vice-President, Clinical Research and Strategy 
jmferrer@lumicell.com 
Phone: 617-571-0592 
 
Protocol Lead Principal Investigator: 
Barbara L. Smith, MD, PhD 
Director, Breast Program 
Massachusetts General Hospital 
55 Fruit Street 
YAW9 
Boston, MA 02114 
Phone: 617-726-6500 
Fax: 617-724-1079 
 
Medical Monitor: Karl Gallegos, M.D. 
kgallegos@lumicell.com 
 
 
 

Pivotal study of intraoperative imaging in breast cancer 
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TABLE OF CONTENTS 
1 
PURPOSE .............................................................................................................................................................. 4 
2 
SUMMARY OF ENDPOINTS ............................................................................................................................ 4 
2.1 
Three co-primary endpoints ............................................................................................................................ 4 
2.2 
Secondary endpoints ....................................................................................................................................... 4 
3 
BACKGROUND ................................................................................................................................................... 5 
3.1 
Study disease ................................................................................................................................................... 5 
3.2 
Rationale ......................................................................................................................................................... 5 
3.3 
Definitions ....................................................................................................................................................... 6 
4 
PRODUCT DESCRIPTION ................................................................................................................................ 7 
4.1 
Intended use .................................................................................................................................................... 7 
4.2 
Proposed indications for use ........................................................................................................................... 8 
4.3 
LUM015 imaging agent................................................................................................................................... 8 
4.4 
LUM Imaging Device ...................................................................................................................................... 9 
4.5 
LUM decision software ................................................................................................................................... 9 
4.6 
Prior clinical studies with the LUM Imaging System in females with breast cancer .................................... 10 
5 
PIVOTAL STUDY DESIGN ............................................................................................................................. 11 
5.1 
Design Summary ........................................................................................................................................... 11 
5.2 
Methods ......................................................................................................................................................... 12 
5.3 
Lumpectomy specimen and cavity walls orientation nomenclature .............................................................. 16 
6 
SUBJECT SELECTION .................................................................................................................................... 17 
6.1 
Eligibility Criteria ......................................................................................................................................... 17 
6.2 
Exclusion Criteria ......................................................................................................................................... 18 
6.3 
Inclusion of Women, Minorities and Other Underrepresented Populations ................................................. 19 
7 
SUBJECT ENROLLMENT ............................................................................................................................... 20 
7.1 
General guidelines for screening and enrollment ......................................................................................... 20 
7.2 
Enrollment process ........................................................................................................................................ 20 
8 
INTERVENTIONAL PLAN .............................................................................................................................. 20 
8.1 
LUM015 administration ................................................................................................................................ 20 
8.2 
General concomitant medication and supportive care guidelines ................................................................ 21 
8.3 
Duration of therapy ....................................................................................................................................... 21 
8.4 
Duration of follow up .................................................................................................................................... 22 
8.5 
Criteria for removal from the study ............................................................................................................... 22 

Pivotal study of intraoperative imaging in breast cancer 
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8.6 
Criteria for stopping the study ...................................................................................................................... 23 
9 
LUM015 FORMULATION AND ADMINISTRATION ................................................................................. 24 
9.1 
Availability .................................................................................................................................................... 24 
9.2 
Administration ............................................................................................................................................... 24 
9.3 
Accountability................................................................................................................................................ 24 
9.4 
Receipt and return of LUM015 and the LUM Imaging Devices .................................................................... 24 
10 Schedule of Events .............................................................................................................................................. 24 
11 SAFETY ............................................................................................................................................................... 26 
11.1 
LUM015 pharmacokinetics ...................................................................................................................... 26 
11.2 
Expected adverse events (associated with LUM015) ................................................................................ 27 
11.3 
Expected adverse device effects (associated with the LUM Imaging System) .......................................... 28 
12 ADVERSE EVENT REPORTING REQUIREMENTS .................................................................................. 28 
12.1 
Definitions ................................................................................................................................................ 28 
12.2 
Procedures for recording and reporting safety ........................................................................................ 30 
12.3 
Reporting requirements ............................................................................................................................ 30 
12.4 
Reporting to Lumicell ............................................................................................................................... 30 
12.5 
Reporting to the Institutional Review Board (IRB) ................................................................................... 31 
12.6 
Reporting to the Food and Drug Administration (FDA) .......................................................................... 31 
12.7 
Reporting to Hospital Risk Management .................................................................................................. 31 
12.8 
Monitoring of adverse events/adverse device effects and period of observation ...................................... 31 
12.9 
Protocol deviations ................................................................................................................................... 32 
13 DATA AND SAFETY MONITORING ............................................................................................................ 32 
13.1 
Data reporting .......................................................................................................................................... 32 
13.2 
Safety review ............................................................................................................................................. 32 
13.3 
Monitoring ................................................................................................................................................ 32 
13.4 
Data Safety Monitoring Board ................................................................................................................. 33 
14 REGULATORY CONSIDERATIONS ............................................................................................................. 33 
14.1 
Protocol review and amendments ............................................................................................................. 33 
14.2 
Informed consent ...................................................................................................................................... 33 
14.3 
Ethics and Good Clinical Practice (GCP) ............................................................................................... 34 
14.4 
Study documentation ................................................................................................................................ 34 
14.5 
Records retention ...................................................................................................................................... 35 
15 STATISTICAL CONSIDERATIONS .............................................................................................................. 35 
15.1 
Analysis Populations ................................................................................................................................ 35 

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15.2 
Definition of truth standard for diagnostic performance evaluation (sensitivity and specificity) ............ 35 
15.3 
Sample Size ............................................................................................................................................... 36 
15.4 
Statistical Methods ................................................................................................................................... 39 
16 PUBLICATION PLAN ...................................................................................................................................... 41 
17 REFERENCES.................................................................................................................................................... 41 
18 APPENDICES ..................................................................................................................................................... 43 
 
 

Pivotal study of intraoperative imaging in breast cancer 
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1 PURPOSE 
The objective of this prospective, multi-center, two-arm randomized, blinded study is to 
demonstrate the safety and efficacy of the LUM Imaging System (LUM015 imaging agent in 
conjunction with the LUM Imaging Device and decision software), in identifying residual cancer 
in the lumpectomy bed of female breast cancer patients. The size of this study is driven by the 
necessary number of truth standard positive events; therefore, we propose an event-driven clinical 
study. Patients will be enrolled until 70 truth standard positive events are reported, up to a 
maximum of 450 patients. 
2 SUMMARY OF ENDPOINTS 
2.1 
Three co-primary endpoints 
• Ratio of patients who have residual cancer found in at least one Lumicell-guided shave 
(also known as therapeutic shave) among all patients. Residual cancer is defined as tumor 
found by pathology in a therapeutic shave after the SOC surgical procedure is completed; 
that is, tumor that current SOC surgery failed to remove. 
• Instrument diagnostic accuracy measured as two separate endpoints of sensitivity and 
specificity on a per-tissue basis. 
2.2 
Secondary endpoints 
a. Proportion of patients with positive margins after standard of care breast-conserving 
surgery who have a LUM Imaging System signal in the cavity above the threshold as 
defined by the tumor detection algorithm (i.e., a positive LUM signal). 
b. Proportion of subjects with pathology-positive margins after standard of care breast-
conserving surgery for whom additional LUM Imaging System-guided shaves resulted in 
pathology-negative margins among patients with positive margins. Note: This endpoint 
also estimates the potential reduction in re-excision surgeries following standard of care 
breast-conserving surgery that resulted from a positive SOC margin. 
c. Proportion of subjects with pathology-positive margins after standard of care breast-
conserving surgery for whom additional LUM Imaging System-guided shaves resulted in 
pathology-negative margins among all patients. 
d. Ratio of patients with negative margins after the SOC procedure who have residual cancer 
found in at least one Lumicell-guided (or therapeutic) shave among patients with negative 
margins. 
e. Ratio of patients with negative margins after the SOC procedure who have residual cancer 
found in at least one Lumicell-guided (or therapeutic) shave among all patients 
f. Mean and median incremental volume (in cubic centimeters) of tissue removed from 
therapeutic shaves: For each patient, absolute shave volume will be calculated as length (c) 
× width (c) × depth (c) for each therapeutic shave with the sum by patient of all therapeutic 
shaves. Subjects with no therapeutic shaves taken will have a therapeutic shave volume of 
0cc. 
g. Mean and median contribution of therapeutic shave volume to total tissue removed. 
h. Comparison of adverse events in subjects that have at least one therapeutic shave versus 
subjects that have no therapeutic shaves. 

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i. Average number of therapeutic shaves taken per subject overall and by type of SOC 
lumpectomy procedure (i.e., lumpectomy with comprehensive shaves vs. lumpectomy with 
or without selective shaves). 
j. Percent of device failures that led to failure of using the LUM Imaging System to capture 
data. 
k. Rate of re-excision procedures as a result of a positive margin status following SOC 
(control arm) and LUM Imaging procedures (device arm). 
l. Number of re-excisions for each patient 
m. Number of re-excisions recommended 
n. Collect exploratory data on tissue types found in therapeutic shaves. 
o. Collect exploratory data on patient reported outcome measures (PROMs). 
p. Adverse events stratified by severity and relatedness to drug/device. 
q. Serious adverse events stratified by severity and relatedness to drug/device. 
r. Adverse events by preferred term (sorted by descending occurrences for each preferred 
term). 
s. Summary of adverse events, overall and split by expectedness to drug/device. 
3 BACKGROUND 
3.1 
Study disease 
For breast cancer lumpectomies, the presence of residual cancer cells left in the tumor bed after 
initial resection is inferred by post-operative margin assessment of the resected tissue by a 
pathologist. For invasive carcinoma and ductal carcinoma in situ (DCIS), a positive margin is 
defined as having tumor present at the inked side of the outermost surface of the lumpectomy 
specimen [1, 2]. However, according to the Society of Surgical Oncology (SSO), for negative 
margins of less than 2mm in patients with DCIS, clinical judgment is recommended to determine 
the need for a second surgical procedure [2]. Positive lumpectomy margins are the most important 
risk factor for local recurrence of breast cancer [1-5] and dictate that a second surgical procedure 
be performed to obtain tumor-free margins. The rates of close or positive margins have been 
reported between 17 to 59% [6-10]. Among the more than 318,000 women expected to be 
diagnosed with breast cancer in the US in 2017, approximately 200,000 underwent lumpectomy 
and approximately a third required additional surgery for positive margins [11]. Thus, a diagnosis 
of positive margins indicates that additional treatments are needed. This places a heavy burden on 
patients and adds significant cost to the healthcare system. 
3.2 
Rationale 
Achieving negative margins during tumor excision is critical to assure that all or most of the cancer 
has been removed from the patient. Current standard of care dictates that tissue removed during 
surgery is analyzed post-operatively for tumor histology and margin assessment by a pathologist 
as described above. This procedure is time consuming, often requiring 7-10 days of pathology 
testing after the operation before margin status is known. In addition, this process is prone to 
sampling errors, as only a finite number of tissue slices can be examined, meaning that only a 
small fraction of the lumpectomy margin surface is assessed, < 1% of lumpectomy surface area by 
some estimates [2]. Thus, a safe method to directly assess the entire tumor bed intraoperatively 
and identify residual microscopic disease for immediate resection intraoperatively would be highly 
beneficial for patients. 

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Lumicell has developed the LUM Imaging System, which consists of a fluorescence-based 
imaging agent (LUM015), a hand-held, wide-field detector (LUM Imaging Device) that can image 
the lumpectomy cavity in seconds, and a tumor detection algorithm that highlights regions 
suspected to contain cancer and displays them on a computer monitor. The LUM Imaging system 
is intended to be used to scan the lumpectomy cavity walls intraoperatively after the resection of 
the main lumpectomy specimen. 
The purpose of the Lumicell Imaging System is to enable surgeons to achieve negative margins 
during the initial surgery and eliminate or reduce the need for re-excision surgeries when compared 
with current standard of care procedures. Lumicell’s system images the entire lumpectomy cavity 
surface in vivo, overcoming tissue handling and sampling limitations of standard pathology 
analysis of resected tissue. The LUM Imaging System provides real-time feedback to the surgeon 
about the status of the lumpectomy cavity walls. 
The LUM Imaging System has been tested in a two-phase Feasibility Study at the Massachusetts 
General Hospital. There were 15 patients in Phase A and 45 patients in Phase B in the study.  Of 
the 11 Lumicell imaged subjects for whom a pathology positive margin followed SOC, the LUM 
Imaging Device detected 9 (82%) of the subjects with residual cancer in the cavity. A multi-site 
Feasibility Phase C study is being conducted to refine and verify the tumor detection algorithm 
and to complete hands on training of surgeons and clinical staff. 
3.3 
Definitions 
3.3.1 Definitions of excised tissue 
• Main specimen: also known as the “lump” or main mass, refers to the primary piece of 
tissue removed during a lumpectomy. Typically, this is the largest piece of tissue 
removed and it is intended to contain most of the tumor. 
• Shave types: pieces of tissue removed from the lumpectomy cavity walls after the main 
specimen is removed. In this study, we define three different types of shaved cavity 
margins (SCMs) below. 
o Selective shaves: shaved cavity margins removed from a specific location of the 
lumpectomy cavity wall based on intraoperative analysis of the intact main 
specimen by methods including X-ray imaging, ultrasound imaging, palpation, 
frozen sections or visual examination. Selective shaves precede all other SCMs 
described below. 
o Comprehensive shaves: shaved cavity margins removed from all available 
surfaces of the lumpectomy cavity walls after resection of the specimen based 
on the SOC for that surgeon/site 
o Therapeutic shaves: shaved cavity margins removed following the guidance of 
the LUM Imaging System; may also be referred to as Lumicell-guided shaves. 
3.3.2 Definition of standard lumpectomy procedure used in this protocol 
Breast conserving surgeries may vary between surgeons and institutions. However, most surgical 
practices perform what is defined in this protocol as a “standard lumpectomy procedure”. This 
procedure consists of the surgeon’s best attempt to remove the main specimen with grossly 
negative margins and may be followed by the removal of selective shaves (see definition above). 
Some institutions have implemented additional margin management techniques such as 
comprehensive shaves, as defined above, to try to lower the rates of positive margins and re-

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excision [12, 13]. Table 1 outlines the surgical procedure options that will be allowed in this study 
to support the primary and secondary endpoints. 
Table 1: Surgical procedures to be included in the SOC arm of this clinical study. 
SOC procedure 
Description 
Basis for margin assessment 
A. Standard 
lumpectomy 
procedure: main 
specimen followed 
by selective shaves 
Most sites in the US practice this 
procedure. The main specimen is 
removed and some selective shaves 
may be removed based on palpation, 
X-ray imaging, frozen sections or 
visual inspection of the intact main 
specimen. 
Outermost surface from a 
given orientation that can 
come from the main specimen 
or a selective shave when a 
shave exists. 
B. Standard 
lumpectomy 
procedure 
followed by 
comprehensive 
cavity shaves 
After the standard lumpectomy 
procedure, a cavity shave is removed 
from all the available orientations. A 
shave from anterior or posterior may 
not be removed if no breast tissue 
remains at these surfaces. 
Outermost surface from a 
given orientation that can 
come from the main specimen 
or a comprehensive shave 
when a shave exists. 
 
3.3.3 Definition of endpoints 
3.3.3.1 Definition of positive margins 
For this protocol, positive margins are defined using the latest consensus from the Society of 
Surgical Oncology as follows: 
• For invasive cancer with or without associated ductal carcinoma in situ (DCIS): cancer 
cells or DCIS present on ink [1] 
• For pure DCIS lesions: DCIS present less than 2 mm from the ink [2] 
3.3.3.2 Definition of re-excisions 
A re-excision is defined as a surgical procedure performed in the ipsilateral breast following the 
primary lumpectomy because of positive margins found from the initial lumpectomy procedure. 
The re-excision procedure can be a separate surgical procedure to excise further breast tissue or a 
mastectomy. 
3.3.3.3 Definition of positive cavity 
After the standard lumpectomy procedure, a positive cavity occurs when tumor is found in a 
therapeutic shave or during a re-excision.  
4 PRODUCT DESCRIPTION 
4.1 
Intended use 
The LUM Imaging System is a combination product consisting of the LUM015 imaging agent and 
the LUM Imaging Device. LUM015 is administered to the patient via intravenous injection 4 ± 2 
hours prior to the first image recorded. The LUM Imaging Device is intended for use in vivo 

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following the excision of the main lumpectomy specimen to detect remaining cancer cells after 
breast conserving surgery. 
4.2 
Proposed indications for use 
The LUM Imaging System is indicated for use in patients undergoing a breast conserving surgery 
(lumpectomy) to remove breast cancer. The LUM Imaging System is not indicated for those 
subjects receiving administration of blue (e.g. methylene blue, isosulfan blue) or green (e.g. 
indocyanine green) dyes for sentinel lymph node mapping procedures prior to the lumpectomy 
procedure. The LUM Imaging System is intended to be used whenever breast tissue is removed, 
histopathology evaluation of the tissue is the standard of care and/or it is essential that the tissue 
margins be examined for completeness of removal using standard surgical procedures. The LUM 
Imaging System is to be used in vivo following the excision of the main lumpectomy specimen to 
assist in locating residual abnormal tissue, therefore, facilitating tumor resection and potentially 
creating negative margins on the outermost surfaces of excised tissue. 
4.3 
LUM015 imaging agent 
Lumicell engineered LUM015, a fluorescence-based imaging agent that accumulates within and 
around cells.  In regions enriched with cathepsin enzymes, such as cancer cells, LUM015 is altered 
to fluoresce when illuminated with 649 nm light. In its nominal state, the fluorescence of LUM015 
is suppressed by an internal quencher molecule (QSY21). The presence of cathepsin enzymes is 
not fully confined to cancer cells; hence, data from this study will help determine the cancer 
localization properties of LUM015.  Once cathepsin enzymes cleave LUM015 at its amino acid 
backbone, the quencher is released and the fluorescent dye (Cy5) in LUM015 emits detectable 
fluorescence when it absorbs red light (Figure 1). The absorption and emission wavelength 
maxima for Cy5 are 649 nm and 670 nm respectively. LUM015 employs a fluorescent molecule 
with excitation and emission in the far red spectrum (> 600 nm wavelength) because in that range 
light can travel effectively through 1mm of tissue and tissue autofluorescence is minimal, allowing 
higher sensitivity due to lower background [14]. 
 
Figure 1: Schematic representation of LUM015. 
Cathepsins are a family of enzymes that are involved in the degradation of the extracellular matrix 
to allow tumor growth and progression. These enzymes are upregulated in most human cancers 
and are also present in tumor-associated macrophages at the tumor’s invasive front [15-19]. Platt 
et al. showed 60-fold higher cathepsin activity in breast cancer tissue than in healthy breast tissue 
[20]. Others report over-expression of cathepsin enzymes (B, K, L and D) in ductal carcinoma in 
situ as well as in invasive carcinomas (lobular and ductal) [16, 20-23]. Also, cathepsin B is 
typically over-expressed in inflammatory breast cancer, one of the most lethal forms of primary 
breast cancer. [24, 25]. The peptide sequence used in LUM015 is a pan-cathepsin substrate 
LUM015
PEG 20K
Fluorophore – Cy5
Quencher – QSY21
Substrate  -GGR-
Spacer

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meaning that it will be cleaved by multiple enzymes of the cathepsin family. Because high activity 
of cathepsin enzymes is found in tumor cells and tumor associated macrophages surrounding the 
tumor at the invasive front, these enzymes provide an excellent marker for activating LUM015 at 
the tumor margin. The fluorescence of LUM015 is then induced and detected with the LUM 
Imaging System to identify cancer and cancer-related cells for immediate resection and to 
distinguish them from adjacent normal tissue. 
4.4 
LUM Imaging Device 
The LUM Imaging Device consists of a computer control unit, monitor and light source mounted 
on a cart, and a hand-held optical head (LUM002/LUM003). The computer control unit collects, 
analyzes (based upon Lumicell’s detection algorithm) and displays the resulting images gathered 
by the imaging head in real-time. The light source provides the illumination to excite the 
fluorescent dye present in LUM015. Light is transferred from the light source to the imaging head 
using an optical fiber bundle. The imaging head (Figure 2) was designed as a lightweight hand-
held tool with a small profile to allow easy maneuverability and limited intrusiveness in the 
operating room. Because incisions and lumpectomy cavities can vary in size, Lumicell offers two 
options for the distal end diameter: LUM002, which has a 2.6 cm field of view along with a 3.1 
cm outer diameter and LUM003, which has a 1.3 cm field of view and a 1.9 cm outer diameter. 
The surgeons will be able to choose which device size to use for any given surgery. These two 
device options were proven to be optically equivalent when imaging freshly excised breast tissue. 
Both imaging heads have a 45° bend at the distal end for examination of the walls of the 
lumpectomy cavity.  
The hand-held optical head will be used within the sterile surgical field.  Consequently, a sterile 
barrier assembly will be provided to cover the optical head, which comes into contact with both 
the surgeon and the patient’s exposed tumor bed. The sterile barrier assembly is installed on the 
LUM Optical Head in the OR using sterile procedures. 
 
Figure 2: (Left) Photo of the LUM Imaging System. (Right) Rendering of the LUM002 Optical Head scanning a 
lumpectomy cavity. The sterile cover over the device is not shown. 
4.5 
LUM decision software 

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The LUM Imaging System is powered by Lumicell’s proprietary decision software. The decision 
software uses an initial set of images acquired from the lumpectomy cavity after the main specimen 
is removed to set the tumor detection threshold. Then, while the surgeon scans the lumpectomy 
cavity walls with the LUM Optical Head, the decision software compares the intensity of an image 
against the tumor detection threshold and identifies whether a region of the image is suspected to 
contain tumor. Regions with fluorescence signal above the threshold are highlighted in the 
computer monitor for the surgeon to see in real-time; that is, there is no delay between the scanning 
of a region and the display of the results from that region.  Figure 3 shows the user interface and 
what the surgeon sees during scanning of the cavity walls. The decision software was developed 
and optimized during Phase A and Phase B of the Feasibility Study in breast cancer patients. 
 
Figure 3: Screen shot of the user interface for the LUM decision software. Regions highlighted in red indicate areas 
suspect to have tumor. 
4.6 
Prior clinical studies with the LUM Imaging System in females with breast cancer 
Following the designation of a device primary mode of action for the LUM Imaging System 
combination product by FDA, Lumicell and collaborators at MGH conducted a Feasibility Study 
in breast cancer patients under an Investigational Device Exemption (IDE). The Feasibility Study 
was divided into Phase A, Phase B and Phase C as described below, and all phases have been 
completed. A multi-site Pivotal Study is underway. 
4.6.1 Summary of three phases of the Feasibility study (all completed) 
• Phase A (n=15 patients): patients were administered with either no LUM015 (5 patients) 
or a dose of 0.5 mg/kg (5 patients) or 1.0 mg/kg (5 patients) 4 ± 2 hours prior to surgery 
and the LUM Imaging System was used to image the lumpectomy cavity before and after 
standard of care cavity shaves. Resected cavity shaves were also imaged. The imaging 
results were compared with pathology analysis of the cavity shaves. The endpoints were: 
(1) select a dose of LUM015 for Phase B; (2) determine the parameters of the tumor 
detection threshold; and (3) acquire safety data. No clinical action was taken by the surgeon 
based on the imaging results. A dose of 1.0 mg/kg was selected for Phase B and all 
subsequent clinical studies in breast cancer. 
• Phase B (n=45 patients):  the tumor detection threshold was implemented and the LUM 
Imaging System was used to scan the lumpectomy cavity to guide the removal of additional 
cavity shaves beyond the standard of care cavity shaves. The endpoints were: (1) evaluate 
and, if necessary, adjust the detection algorithm parameters, (2) adjust, if necessary, the 
protocol for the pivotal trial, and (3) collect safety data. 

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• Phase C (multi-center evaluation, n=234 patients):  the tumor detection threshold and 
the LUM Imaging System was evaluated at multiple sites to (1) collect data to refine and 
verify the tumor detection algorithm, (2) complete hands-on training of surgeons and 
clinical staff that will be participating in the pivotal study, (3) identify and address any site-
specific or user-specific issues for using the LUM Imaging System in breast cancer 
surgeries, and (4) collect safety and efficacy data. 
Once a surgeon was trained in the use of the LUM Imaging System during Phase C of the 
Feasibility Study, the tumor detection algorithm was locked and this protocol has been initiated, 
the surgeon may begin enrolling patients for the pivotal study. Any surgeon or site that did not 
participate in the Phase C study will be required to undergo training and complete a modified 
proficiency program before starting enrollment for this pivotal study. 
No serious adverse events were observed in both Phase A and Phase B of the Feasibility Study. The 
only adverse event noted in these two phases was a temporary blue discoloration at the injection 
site for LUM015 that resulted from extravasation of LUM015 during injection (see details in 
section 11.2) One patient enrolled in the Phase C study, with known hypersensitivity to contrast, 
experienced an anaphylactic reaction to the LUM015 injection. The patient recovered in <24 hours. 
No other related serious adverse events have been reported to date. 
5 PIVOTAL STUDY DESIGN 
5.1 
Design Summary 
This is a prospective, multi-center, two-arm, randomized, blinded clinical trial.  All eligible 
subjects are injected with LUM015. All eligible subjects shall follow the day of surgery workflow 
illustrated in Figure 4. 

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Figure 4: Surgery workflow diagram. A detailed description of each step in the surgical workflow is provided in 
sections 5.2.3 - 5.2.9 below. 
5.2 
Methods 
5.2.1 Establishing a patient in the electronic data capture system (EDC)  
All consented patients should be entered into the electronic data capture system prior to surgery.  
5.2.2 Collection of baseline Patient Reported Outcome Measures Data 
After the patient has consented to participate and has consented to the collection of Patient 
Reported Outcome Measures (PROMs) Data, prior to surgery start, each enrolled subject should 
complete this baseline survey collecting data to support an evaluation of PROMs. Baseline 
evaluations will be electronically collected using the EDC system at any time after the patient 
consented to participate in the study and prior to their lumpectomy procedure.  If the patient has 
not yet completed their survey at the time of injection, the study site should facilitate and remind 
the patient to complete their survey.  The patient should not complete the baseline survey after the 
lumpectomy procedure.  The completion of the survey is not a requirement to be enrolled into the 
study. Alternatives to electronic distribution of the surveys may be implemented. 
5.2.3 LUM015 Injection and Randomization 
LUM015 injection
Main specimen 
resection
Lumicell cavity 
initialization
Surgeon may take SoC shaves, but must 
image cavity wall(s) where the SoC shave 
will be taken before taking the shave.
Randomization 
revealed
to proceed
Lumicell-
guided shaves
Pathology 
assessment of 
resected tissue
not to 
proceed
Pathology 
assessment of 
resected tissue
10 
1 
: 

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All consented and eligible patients will be injected with LUM015 at a dose of 1.0 mg/kg 4 ± 2 
hours prior to the first image recorded with the LUM Imaging System during the lumpectomy 
procedure. After injection of Lumicell, prior to surgery, the clinical site must update the subject in 
the EDC to document the subject’s status as ‘enrolled’. Once a subject is classified as ‘enrolled’, 
the subject will be randomized to either the control arm or the treatment arm of this study. Although 
the subject is randomized at the time of enrollment, the randomization will not be revealed to the 
study team until after the standard of care lumpectomy is completed. 
5.2.4 Main specimen resection 
The surgeon shall remove the main specimen per standard of care with the intention of achieving 
grossly negative margins. See Appendix A for guidelines on how to handle and ink the main 
specimen. Before the main specimen resection is complete, the LUM Imaging Device shall be 
initialized and the sterile barrier shall be applied according to the Instructions For Use.  A Study 
Worksheet provided by Lumicell shall be completed by the clinical site throughout the surgery to 
collect study related information. 
5.2.5 Lumicell cavity initialization 
The Lumicell cavity initialization shall be performed by recording images of the lumpectomy 
cavity walls per Instructions For Use manual to set the tumor detection threshold specific for that 
patient. 
5.2.6 Standard of care shaves 
Before removing standard of care comprehensive shaves or selective shaves (based on palpation 
of the main specimen or cavity walls, X-ray imaging of the intact main specimen, intraoperative 
frozen section pathology, or visual examination), the surgeon shall record a LUM image from all 
the orientations from which an SOC shave will be removed. At this time, the tumor detection 
algorithm will be “off” to allow fluorescence visualization and navigation of the lumpectomy 
cavity without highlighting of suspected tumor that may bias normal standard of care. 
5.2.6.1 Prior to obtaining any SOC shaves or associated images, the surgeon shall document their 
intent of obtaining SOC shaves on the study worksheet. 
5.2.6.2 When there is no tissue available to be removed from a given orientation (e.g., too close 
to skin or too close to the chest wall), no LUM image shall be collected from that 
orientation.  This information must be documented.  
5.2.6.3 The surgeon shall place the optical head at the cavity location where a standard of care 
shave will be taken, instruct the computer operator when to save the image and define the 
image orientation. 
5.2.6.4 The surgeon shall take the standard of care shave from the imaged location. 
5.2.6.5 The surgeon shall repeat steps 5.2.6.1-5.2.6.4 for all cavity location(s) where a standard 
of care shave will be taken.  
5.2.6.6 The resected tissue(s) shall be handled and named according to the Appendix B. 
Standard of care margin assessment will be made by pathology on all the tissue removed during 
the standard of care procedure. If a positive margin is determined, this subject will be included in 

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the positive margin population. The intent of the standard of care lumpectomy procedure is to 
achieve negative margins. 
5.2.7 Randomization revealed 
After completion of standard of care, the study coordinator (or other authorized person) shall log-
in to the EDC system to reveal whether the patient will receive Lumicell image-guided 
intervention. Randomization will be performed at a ratio of 10:1; for every 10 patients undergoing 
Lumicell imaging directed tissue resection after standard of care (“to proceed”), 1 patient shall 
complete surgery following standard of care alone (“not to proceed”). The randomization is 
intended to mitigate potential surgeon bias, and the 10:1 ratio was chosen based on prior clinical 
studies that supported imaging agent efficacy trials.    
5.2.8 Lumicell procedure (only patients randomized to the intervention arm) 
After the standard of care is completed for patients randomized “to proceed” with the Lumicell 
intervention, the surgeon will scan the tumor bed to collect images of the cavity walls and remove 
therapeutic shaves as indicated by the LUM decision software (refer to the Instructions For Use 
manual for details). The software will automatically turn on the tumor detection algorithm to allow 
visualization and navigation of the lumpectomy cavity with highlighting of suspected tumor by 
the tumor detection algorithm. 
5.2.8.1 When there is no tissue available to be removed from a given orientation (e.g., too close 
to skin or too close to the chest wall), no LUM image shall be collected from that 
orientation.  This information must be documented.  
5.2.8.2 The surgeon shall scan the cavity and generate images from each orientation. Images 
should be generated and saved for both LUM positive and negative results. 
5.2.8.3 The surgeon shall take a Lumicell shave from each imaged location indicated as 
“positive” by the LUM decision software. 
5.2.8.4 A maximum of two (2) Lumicell shaves may be taken from any one orientation. 
Additional Lumicell shaves beyond 2 per orientation will constitute a protocol violation. 
5.2.8.5 The resected tissue(s) shall be handled and named according to the Appendix B. 
If a shave is not taken when indicated by the LUM Imaging System or a Lumicell image is not 
recorded as described above, a protocol deviation will be recorded with exception as described in 
section 5.3.1. If images are not saved in all orientations, a protocol deviation will be recorded 
unless there is no enough tissue left to take a shave (see 5.2.8.1). The reason for not taking a shave 
when indicated by the Lumicell system shall be recorded. 
5.2.9 Pathology 
Pathology shall report on the following criteria for each sample of breast tissue excised during the 
surgery (main specimen and shaves). It is particularly important that the pathologist reports the 
tumor distance(s) to the specimen margin(s) for each specimen excised during surgery.  Reporting 
on tumor distances to final margins alone will not allow for determination of study endpoints. 
o Type of resection (e.g. lump or shave) 
o Tissue dimensions (LxWxH) 
o Tissue Weight (g), if available 

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o Presence/absence of tumor (Invasive Lobular Carcinoma (ILC), Invasive Ductal 
Carcinoma (IDC), IDC with Ductal Carcinoma in situ (DCIS), DCIS only or any 
combination of these) 
o tumor distance(s) to inked margin(s)     
o tumor grade 
o tumor size 
o Other tissue type(s) present, including: 
 LCIS 
 Atypical ductal hyperplasia 
 Usual ductal hyperplasia 
 Inflammation 
 Fibroadipose only 
 Fibroadenoma 
 Papilloma 
 Dense Fibrous 
 Fibrocystic change 
 Apocrine metaplasia 
 Radial scar lesions 
 Biopsy site changes 
 Adenosis 
 
The final margin assessment for a patient is based on the outermost surface. The pathologist will 
be blinded to the type of shave (Lumicell-guided or standard of care) when conducting the 
pathology evaluation. 
5.2.9.1 Data collected from re-excision surgery 
Margin assessment of the outermost resection surface from the initial surgery will be used to 
inform the surgeon whether a patient should receive re-excision surgery. Re-excision surgery data 
as well as pathology data from re-excision surgery will be collected. Data will be collected on 
patient-provider interaction and discussions when evaluating the recommendation for re-excision.  
5.2.10 Follow-up 
Subjects will be followed, and data collected as described in section 8.4. 
5.2.11 Safety observations 
All subjects will be observed to assess the safety of LUM015 with standard preoperative, 
intraoperative and postoperative monitoring after receipt of the LUM015 injection. The subject 
will have a final safety assessment at the first post-operative visit, where a blood draw will occur, 
and lab values evaluated for clinically significant values that differ from the subject’s baseline 
values. All subjects will continue their enrollment and be followed in the study until their medical 
team determines that no further surgical intervention is required.  
5.2.12 Other general procedures and injection of LUM015 
For subjects with non-palpable tumors, an ultrasound, mammogram or MRI-guided localization 
procedure may be performed prior to or the same day as the surgery. Also, patients having a 
sentinel lymph node (SLN) mapping procedure may be injected with the radiotracer Technetium-

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99 (Tc-99) per standard of care. LUM015 may be injected before or after any of these procedures, 
as long as the injection occurs 4 ± 2 hours prior to the first image recorded. 
Prior to the surgery, the LUM Imaging System will be positioned in the operating room and an 
initialization procedure will be conducted to ensure that the performance parameters of the device 
are within defined specifications. If during the initialization procedures, the performance 
parameters are outside the defined specification, the user is prompted to discontinue use of the 
device. If the error cannot be fixed within a reasonable time in the operating room, these patients 
will receive standard of care treatment and will not be imaged with the LUM Imaging Device. 
These patients will be followed and monitored for safety the same way as those patients that 
undergo imaging with the LUM Imaging Device. The patients that are not imaged with the LUM 
Imaging Device will be included in the safety cohort and will count towards device failure rate. 
To avoid excessive tissue resection based on LUM015 signal, surgeons are not to take more than 
2 therapeutic shaves in a given orientation. 
5.3 
Lumpectomy specimen and cavity walls orientation nomenclature 
Throughout this protocol, reference is made to the orientation of the main specimen, the SCMs 
and the lumpectomy cavity walls. When a lumpectomy is performed, there are typically 6 surfaces 
defined for orienting the main specimen and SCMs for final margin assessment. Figure 5 shows 
a schematic representation of the nomenclature for the lumpectomy cavity margins for a right-
sided breast lumpectomy, showing 5 orientations. The sixth orientation (not shown in the figure) 
is the “anterior” margin. Shaved cavity margins removed under the guidance of the LUM Imaging 
System will be named “therapeutic shaves” to distinguish them from standard of care SCMs. Please 
see Appendix B for the guidelines on naming the resected tissue.  Excised tissue should be stitched 
and inked according to Appendix A. 
 
Figure 5: Schematic representation of the surfaces of the lumpectomy cavity walls (white circle). The posterior 
margin is nearest the fascia of the pectoral muscle. The anterior margin (not shown) is nearest the skin. 
5.3.1 Guidance on removing therapeutic shaves 
Therapeutic shaves should be removed anytime the LUM Imaging System indicates signal above 
the threshold (LUM positive signal shown in red in the computer screen). However, if there is not 
enough tissue to be removed (e.g. too close to skin, too close chest wall), a Lumicell image shall 
not be recorded and a therapeutic shave shall not be removed. This should be documented. Protocol 
deviations for not imaging and for not obtaining a therapeutic shave will not be issued when tissue 
is not obtained because there is not enough tissue to be removed. 
5.3.2 Data collection 

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Clinical sites are expected to collect and enter data into the electronic case report form.  Certified 
copies of applicable source documents are to be submitted to Lumicell, which include but are not 
limited to pathology reports for the lumpectomy and study procedure in addition to pathology reports 
for any re-excision surgeries.  Additional source documents may be used to collect study-specific 
data on the day of surgery or during follow-up. 
5.3.2.1 Patient Reported Outcome Measures (PROMs) 
Survey data will be collected directly from the patient via an electronic survey tool. Patients who 
consent to the collection of PROMs will provide an email address at the time of consent. This 
email address will be entered into the electronic data capture system, but will be blinded to the 
Sponsor and Sponsor representatives and only available to database administrators and the clinical 
site. Surveys will be collected at four time points: (1) baseline (before lumpectomy), (2) standard 
of care follow-up after lumpectomy, (3) three months post lumpectomy and (4) six months post 
lumpectomy (± 6 weeks).  Data to be collected may include information about the patient’s breast 
satisfaction (cosmesis) and the patient’s feelings about their breast cancer/breast cancer surgery 
(“cancer worry”). A validated survey tool developed by Memorial Sloan Kettering and McMaster 
University called the Breast-Q will be used to collect PROMs. Alternatives to electronic 
distribution of the surveys may be implemented. 
5.3.3 Sentinel lymph node mapping procedures 
Blue dyes commonly used for SLN mapping have fluorescence absorption and emission spectra 
that overlap with those from Cy5 (dye conjugated to LUM015). When blue dyes are used for SLN 
mapping, they are injected intra-tumoral or peri-tumoral soon after the patient is put under 
anesthesia and prior to the lumpectomy procedure. Therefore, patients planned to have injection 
of blue dyes for SLN mapping are excluded from this study. 
As indicated in section 5.2.12, patients having SLN mapping procedures may be injected with the 
radiotracer Tc-99. In the event that not enough signal is produced from Tc-99, the surgeon may 
elect to inject a blue dye to assist in the mapping procedure. If injection of the blue dye happens 
before the LUM imaging procedure is completed, the subject will be excluded from the efficacy 
cohort but will remain in the safety analysis cohort. 
5.3.4 Potential long-term data collection 
Subject’s participation in this pivotal study will be over after completing the planned follow-up in 
section 5.2.10.  However, there may be additional information about the subject’s cancer status 
that will be helpful to the study sponsors after the research study is complete. As part of 
participating in this research, the subject shall be asked to allow the researchers to access the 
patient’s medical records for approximately five years after the initial breast cancer surgery. A 
separate IRB approval may be required to collect this data at a later time under a different protocol. 
6 SUBJECT SELECTION 
6.1 
Eligibility Criteria 
Subjects must meet the following criteria on screening examination to be eligible to participate in 
the study: 
6.1.1 Subjects must have histologically or cytologically confirmed primary invasive breast cancer, 
ductal carcinoma in situ (DCIS) or primary invasive breast cancer with a DCIS component. 

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The methods for obtaining the histological samples can include core needle biopsies or fine 
needle biopsies. Subjects who had diagnostic open surgical biopsies are excluded from 
participation. 
6.1.2 Female, age of 18 years or older. Because no dosing or adverse event data are currently 
available on the use of LUM015 in subjects <18 years of age, children are excluded from 
this study. 
6.1.3 Subjects must be scheduled for a lumpectomy for a breast malignancy. 
6.1.4 Subjects must be able and willing to follow study procedures and instructions. 
6.1.5 Subjects must have received and signed an informed consent form. 
6.1.6 Subjects must have no uncontrolled serious medical problems except for the diagnosis of 
breast cancer, as per the exclusion criteria listed below. 
6.1.7 Subjects must have organ and marrow function within limits as defined below: 
• Leukocytes > 3,000/mcL 
• Platelets > 75,000/mcL 
• total bilirubin within normal institutional limits 
• AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal 
• Creatinine ≤ 1.5 mg/dL or creatinine clearance > 60 mL/min/1.73 m2 for subjects with 
creatinine levels above institutional normal. 
6.1.8 Subjects with ECOG performance status of 0 or 1.   
Note: Subjects with a history of multiple drug allergies, atopic subjects, and subjects with atopic 
syndrome are eligible for the study but should be pre-medicated according to institution standards 
prior to injection with the LUM015 imaging agent. 
6.2 
Exclusion Criteria 
Subjects who exhibit any of the following conditions at screening will not be eligible for admission 
into the study. 
6.2.1 Subjects who have been diagnosed with bilateral breast cancer and are undergoing a bilateral 
resection procedure. 
6.2.2 Subjects who are pregnant at the time of diagnosis of their breast cancer; this exclusion is 
necessary because the teratogenic properties of LUM015 are unknown. Because there is an 
unknown but potential risk of adverse events in nursing infants secondary to treatment of the 
mother with LUM015, breastfeeding should be discontinued if the mother is treated with 
LUM015. 
6.2.3 Subjects who are sexually active and not willing/able to use 2 medically acceptable forms of 
contraception (hormonal, barrier method of birth control, abstinence) upon entering the study 
and for 60 days after injection of LUM015. Should a woman become pregnant or suspect she 
is pregnant while participating in this study, she should inform her treating physician 
immediately. Breast cancer patients are routinely advised against becoming pregnant during 
treatment, so this requirement does not differ from standard of care. 
6.2.4 Subjects who have taken an investigational drug within 30 days of enrollment. 

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6.2.5 Subjects who will have administration of methylene blue or any dye for sentinel lymph node 
mapping on the day of the surgery prior to imaging the lumpectomy cavity with the LUM 
Imaging Device. 
6.2.6 Subjects who have not recovered from adverse events due to other pharmaceutical or 
diagnostic agents. 
6.2.7 Subjects with uncontrolled hypertension defined as persistent systolic blood pressure > 180 
mm Hg, or diastolic blood pressure > 110 mm Hg; those subjects with known HTN should 
be stable with controlled HTN while under pharmaceutical therapy. 
6.2.8 History of allergic reaction to polyethylene glycol (PEG). 
6.2.9 History of allergic reaction to any oral or intravenous contrast agents. 
6.2.10 Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, 
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, COPD 
or asthma requiring hospitalization within the past 12 months, or psychiatric illness/social 
situations that would limit compliance with study requirements. 
6.2.11 HIV-positive individuals on combination antiretroviral therapy are ineligible because of the 
potential for pharmacokinetic interactions with LUM015. 
6.2.12 Any subject for whom the investigator feels participation is not in the best interest of the 
subject. 
6.2.13 Subjects undergoing a second lumpectomy procedure because of positive margins in a 
previous surgery prior to entering this study. 
6.2.14 Subjects with post-biopsy hematomas greater or equal to 2 cm that are visible on physical 
exam or detected during pre-operative observations. 
6.2.15 Subjects with prior ipsilateral breast cancer surgeries, mastectomies, breast reconstructions 
or implants. 
6.2.16 Subjects with prior ipsilateral reduction mammoplasties (breast reductions) performed less 
than 2 years prior to enrollment to this study. 
6.2.17 Subjects previously treated with systemic therapies to treat the cancer to be removed during 
this clinical investigation, such as neo-adjuvant chemotherapy or hormonal therapy. 
6.2.18 Subjects undergoing breast conserving surgery whose resected specimen (main lump, 
shaves, or any other resected tissue) will be evaluated with frozen section after the Lumicell-
guided removal of shaves. 
Note: It is unknown whether neoadjuvant radiation therapy affects the tumor environment and its 
response to LUM015; thus, patients previously treated with neoadjuvant therapy should be excluded 
per 6.2.17. 
6.3 
Inclusion of Women, Minorities and Other Underrepresented Populations 
As this study is to test the efficacy of an intraoperative imaging technology in female breast cancer 
subjects, all of the subjects will be women. Males with breast cancer (<1% of breast cancer 
patients) usually undergo mastectomy procedures and only rarely have lumpectomies, and thus are 
not eligible for this study. 

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7 SUBJECT ENROLLMENT 
7.1 
 General guidelines for screening and enrollment 
Patients who have consented to participate in the study will be screened against the eligibility 
criteria.  Patients who do not meet the inclusion/exclusion criteria listed in the protocol will fail 
screening and not be eligible to participate in the study. The subject is not considered enrolled into 
the study until written Informed Consent is obtained, the patient is confirmed as eligible per 
inclusion and exclusion criteria, and the investigational product has been administered (Study Day 
One).   
Clinical sites are asked to keep comprehensive Screening and Enrollment logs and provide these 
logs to Lumicell on a regular basis.  
7.2 
Enrollment process 
Patients who consent to participate in this study should be evaluated for eligibility.  All patients 
who consent should be entered into the electronic data capture (EDC) system.  Screening procedure 
data should be recorded in the EDC. The site study team should notify Lumicell of a potential 
candidate for the study and expected surgery date after the subject has been consented. 
The enrollment procedures are as follows: 
1. Obtain written informed consent from the subject prior to the performance of any study 
related procedures or assessments. 
2. Assign the subject a study subject ID number and enter the subject in the EDC.  The 
numbers should follow the Lumicell assigned format as described at the Site Initiation 
Visit in compliance with the Case Report Form nomenclature. All patients who 
consent should be entered into the electronic data capture (EDC) system.   
3. Confirm protocol-specific eligibility using the eligibility assessment documented in the 
subject’s medical/research record. To be eligible for enrollment to the study, the 
subject must meet each inclusion and have none of the exclusion criteria listed 
in the eligibility section of this protocol. 
4. Notify Lumicell clinical team of eligible subject status and date of proposed surgery. 
5. The subject is considered ‘enrolled’ once they have been administered LUM015 (day 
of surgery) 
8  INTERVENTIONAL PLAN 
 
8.1 
LUM015 administration 
The investigational imaging agent LUM015 will be administered at the surgical center or hospital 
4 ± 2 hours prior to the first image recorded. See section 9 for more details about the preparation 
and administration of LUM015.  
No investigational or commercial agents or therapies other than those described in this protocol 
may be administered with the intent to image the subject’s malignancy intraoperatively. 
As per IV injection standard of care, all subjects will be observed for signs of extravasation, or 
allergic reaction following administration of LUM015 to monitor for adverse pharmacological 
activity related to the investigational agent. If extravasation is suspected or confirmed, the injection 

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must be stopped immediately and reported to Lumicell. All study safety assessments will continue 
until the first post-operative visit (approximately 2-3 weeks after surgery). 
If there is evidence supporting that extravasation of LUM015 injection occurred, then that patient 
will be excluded from the efficacy cohort. However, the patient will be included in the safety data 
analysis. 
If the patient is experiencing an allergic reaction to LUM015 administration, the injection should 
be stopped immediately, and the following lab values should be obtained: 
• Histamine 
• Total Blood Complement 
• Tryptase levels 
The blood draw for each of these tests should be done as soon as possible after the start of the 
reaction and again at 30 minutes post start of the reaction. If an immediate blood draw is not 
possible, collect a 30-minute blood draw at minimum. Each blood specimen should be processed, 
packaged and shipped to the contracted central laboratory for this study.  Specific instructions on 
collection, processing, and shipping can be found in the training materials associated with this 
study. 
In case of an allergic reaction to LUM015, sites should not discard any residual drug remaining in 
the used syringe. This drug should be stored at -20 degrees C until a Lumicell representative 
notifies your site of how to proceed with the used syringe.  If this process conflicts with site specific 
SOPs, the clinical site should notify Lumicell in advance of study start that residual drug will not 
be able to be maintained.  
8.2 
General concomitant medication and supportive care guidelines 
A complete listing of all medications (including non-prescription, vitamins, herbal products and 
essential oils) currently being taken on a regular basis prior to surgery will be obtained at screening 
and updated as needed at enrollment and at the post-operative follow-up visit. Medications 
administered during the study related surgery should be recorded. Concomitant medications should 
be collected for up to 2 weeks after LUM015 injection and study related surgery. Concomitant 
medications should only be collected after this time point if a related AE/SAE is reported during 
the follow-up period. Concomitant medications will be recorded in the medical record and case 
report form. 
8.3 
Duration of therapy 
The imaging agent LUM015 will be injected as a single dose 4 ± 2 hours prior to the first image 
recorded. There is no recurrent administration of the imaging agent. The treatment ends after the 
surgery is completed. Subjects may be discontinued by the principal investigator at any time for 
any of the following reasons: 
• unacceptable adverse event or adverse device effect 
• administrative reasons, such as imaging agent no longer available 
• subject noncompliance, 
• safety concern, 
• subject decides to withdraw from the study, or 

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• general or specific changes in the subject's condition render the subject unacceptable for 
further treatment in the opinion of the treating investigator. 
8.4 
Duration of follow up  
Subjects will continue their enrollment and be followed in the study until their medical team 
determines that no further surgical intervention is required and their post-operative follow-up and 
post-operative blood sample has been completed or until resolution of any reported adverse event 
related to the study intervention.  
When attending their first post-operative visit a blood sample will be collected for a CBC with 
differentials (red blood cells, white blood cells including neutrophils, lymphocytes, monocytes, 
basophils, and eosinophils, and platelets) and serum chemistry (alkaline phosphatase, total 
bilirubin, BUN, calcium chloride, glucose, potassium, total protein, SGOT [AST], SGPT [ALT], 
sodium and creatinine/creatinine clearance) tests to assess for possible adverse events. At the time 
of the visit, the patient will be interviewed to determine any potential adverse events.  Subjects 
with adverse events that are determined to be possibly related to the investigational product will 
be followed until resolution or stabilization of the adverse event.  This visit occurs per the standard 
of care post-operative visit schedule; there is no protocol specified window.  In the event a post-
operative standard of care visit does not occur, the reason for no visit should be documented and 
the patient should be contacted by the research staff to be interviewed for adverse events. 
For subjects who opt to participate, PROMs will be collected via electronic survey at four time 
points: (1) baseline (before lumpectomy), (2) standard of care follow-up after lumpectomy, (3) 
three months post lumpectomy and (4) six months post lumpectomy. Surveys will be sent to the 
study subject via a secure portal associated with the electronic data capture (EDC) system. 
Alternatives to electronic distribution of the surveys may be implemented. Patients who are 
participating in the completion of the PROMs survey data will not have new adverse events 
collected or reported after the follow-up period has concluded as described in this section.  
8.5 
Criteria for removal from the study  
Subjects will be removed from study when any of the criteria listed in Section 6.2 applies. The 
reason for study removal and the date the subject was removed must be documented in the study-
specific case report form (CRF). A subject removed from the study will be given standard of care 
treatment. Subjects removed from the study prior to dosing do not count toward total enrollment 
numbers; they are considered “screen failures”.   
Individual patients may be discontinued from the study by the Investigator or Lumicell at any time 
if either determines that it is not in the best interest of the patient to continue (e.g., continuation in 
the study represents a serious medical risk to the patient). This may include, but is not limited to, 
the presence of serious, life-threatening adverse events, unanticipated adverse device effects, 
adverse events, or adverse device effects that are unacceptable in nature, severity, or frequency as 
assessed by the Investigator. 
Patients must not be enrolled if, prior to study drug injection, they become pregnant or withdraw 
consent. While patients will be encouraged to complete the study, they may voluntarily withdraw 
at any time. 
In the event of unusual or life-threatening complications, participating investigators must 
immediately notify Lumicell. 

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An individual is considered to be a participant once she is enrolled or entered into the study.  This 
would include subjects that are eligible for contributing data to the scientific aims and consented 
for participation, including individuals who subsequently dropout.  Subjects who are screened for 
participation but are not eligible (because of not meeting inclusion/exclusion or because LUM015 
was not injected) or who do not consent would not be considered as participants. 
Prospective exclusions from the efficacy analysis population will include: 1) patients for whom 
the LUM015 systemic injection was not performed properly and (2) major protocol deviations. 
These patients will be included in the safety analysis cohort. 
8.6 
Criteria for stopping the study 
The events listed below are potential stopping rules criteria for the study. Any event listed below 
will be reviewed by the Data Safety Monitoring Board and may be deemed as a stopping criterion 
for the study. If the study is stopped, no additional patients will be recruited, dosed or imaged until 
the Data Safety Monitoring Board has approved the study to continue. 
• Recommendation by the Data Safety Monitoring Board after evaluation of cumulative 
safety reviews 
• Any death probably or definitely related to the treatment with LUM015 or the Imaging 
Device. 
• Any other event that is deemed unacceptable in nature, severity, or frequency as 
assessed by the Data Safety Monitoring Board. 
• Data Safety Monitoring Board recommendation after unexpected event  
In addition to routine Data Safety Monitoring Board meetings, an ad-hoc meeting will occur if the 
occurrence of allergic reactions occurs more frequently than the expected rate.  The DSMB will 
review details of the events and will generate a recommendation for study continuation or 
termination.  
In the case that a safety event requiring enrollment suspension occurs, a prompt cumulative review 
of safety data and the circumstances of the event in question will be conducted to determine 
whether recruitment can be resumed, whether the protocol should be modified, or whether the 
study will be discontinued permanently. The FDA and reviewing IRB must be notified of any 
event that triggers suspension of enrollment in this study. If enrollment is suspended for safety 
reasons and it is deemed appropriate to resume the study, approval from the Data Safety 
Monitoring Board must be obtained prior to resuming the study. The FDA and reviewing IRB will 
be notified when enrollment in this study is resumed. 
Regardless of whether recruitment is continued or not, all subjects injected with LUM015 or who 
were imaged with the LUM device at the time of study-stopping criteria were met will continue to 
be followed for safety. 
In addition to the safety stopping rules outlined above, Lumicell may suspend or terminate this 
study at any time. The reasons for temporarily suspending or terminating the study may include 
but are not limited to the following: 
• Subject enrollment is unsatisfactory 
• Non-compliance that might significantly jeopardize the validity or integrity of the study. 
• Lumicell decision to terminate development. 

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9 LUM015 FORMULATION AND ADMINISTRATION 
Complete instructions for the preparation and administration of LUM015 can be found in the 
Lumicell Pharmacy Manual. A description of LUM015 including storage and stability information, 
handling, and administration in also found in Lumicell Pharmacy Manual and Investigator’s 
Brochure. 
9.1 
Availability 
LUM015 is an investigational agent and will be supplied free-of-charge from Lumicell, Inc. 
9.2 
Administration 
LUM015 is administered over 3 minutes as a single dose of 1.0 mg/kg via peripheral intravenous 
(IV) injection in 0.45% Sodium Chloride Injection, USP, 4 ± 2 hours prior to the first image 
recorded. The IV line must be flushed with 10-20 mL of normal saline just prior to injection of 
LUM015 and the injection is immediately followed by a saline flush of 10-20mL. If extravasation 
is suspected or confirmed, the injection must be stopped immediately and reported to Lumicell. 
Per Principal Investigator’s discretion, in order to protect subjects from potential anaphylactic 
reaction, prophylactic treatment with diphenhydramine may be administered. 
In case of an allergic reaction to LUM015, sites should not discard any residual drug remaining in 
the used syringe. The syringe/used drug should be stored at -20°C until a Lumicell representative 
notifies your site of how to proceed with the used syringe. 
9.3 
Accountability 
The investigator, or a responsible party designated by the investigator, must maintain a supply 
accountability record of the inventory and disposition of Investigational Product, including 
LUM015, camera covers (also known as sterile barriers), and the imaging device. Ancillary 
clinical supplies will be distributed. Receipt and return should be documented, when applicable. 
9.4 
Receipt and return of LUM015 and the LUM Imaging Devices 
A drug inventory will be maintained by the clinical site’s pharmacy. The inventory will include 
details of the LUM015 received and a clear record of when dispensed and for which subjects. This 
inventory record shall indicate the quantity and disposition of all investigational materials on hand 
at any time during the study. 
LUM Imaging Devices will be assembled by Lumicell personnel and Instructions For Use (IFU) 
will be provided. Lumicell personnel will train the clinical staff on using the LUM Imaging 
System. Each clinical site investigator will maintain a device accountability record to document 
receipt and return of the LUM Imaging Devices. 
At the end of the study, unused supplies of LUM015 and the investigational devices must be 
returned to Lumicell. A Lumicell representative will advise you when to return the supplies, as 
well as the proper shipping methods.  Any LUM015 destroyed according to institutional policies 
will be documented.  LUM015 should only be destroyed instead of returning to Lumicell if written 
instruction to do so is provided by Lumicell.  
10 Schedule of Events 

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Baseline evaluations are to be conducted within 8-weeks prior to subject enrollment. The breast 
cancer diagnosis is not considered a baseline evaluation. All baseline assessments must be 
performed prior to administration of any study agent.  
Table 2: Schedule of events. 
Pre-
Enrollment /Screening 
Day 1 / 
Enrollment 
~2-14 days 
after surgery 
Routine 
follow up visit 
3-month 
PROM survey 
collection 
6-month 
PROM survey 
collection 
Informed consent 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Radiologic 
evaluation* 
X 
 
 
 
 
 
Physical exam (Ht, 
Wt, VS) 
X 
 
 
 
 
 
Pregnancy 
test (serum 
or urine) 
Xb 
 
 
 
 
 
CBC 
with 
differentials 
X 
 
 
X 
 
 
Serum chemistry a 
X 
 
 
X 
 
 
Concomitant 
Medications 
X 
X 
 
X 
 
 
Adverse 
event/adverse 
device 
effect 
evaluation 
 
X 
 
X 
 
 
Patient 
Reported 
Outcome Measures
Survey** 
 
     X** 
 
X 
X 
X 
LUM015 
administration 
 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Intraoperative 
imaging*** 
 
X 
 
 
 
 
Margin assessment 
 
 
X 
 
 
 
*: Radiologic Evaluations are not required if not part of the patient’s medical history 
**: PROs are optional for enrollment. The baseline evaluation can be completed by the subject at any time prior to the lumpectomy 
procedure. A validated survey tool, the Breast-Q, will be used to collect the majority of the PROMs. 
***: If subject is randomized into the device arm 
a: Albumin, alkaline phosphatase, total bilirubin, BUN, calcium, chloride, glucose, potassium, total protein, SGOT  [AST], SGPT 
[ALT], sodium and creatinine/creatinine clearance.  
b: Serum or urine pregnancy test (women of childbearing potential) 
 

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11 SAFETY 
A Phase 1 IND study in sarcoma and breast cancer patients was completed at Duke University 
Medical Center. The primary endpoint of this study was to evaluate the safety of the LUM015 
drug component. As a secondary endpoint, the signals from normal and tumor tissue were 
measured ex vivo using the LUM Imaging Device component. Twelve (12) sarcoma patients and 
three (3) breast cancer patients (invasive ductal carcinoma) were injected with LUM015 at doses 
ranging from 0.5 mg/kg to 1.5 mg/kg with no adverse pharmacological activity reported.  The only 
noticeable effect in the study subjects was blue/green discoloration of urine, which resolved within 
12-24 hours post injection for most patients. 
Three feasibility studies have been completed in breast cancer with 294 patients enrolled  (n=15 
in Phase A, n=45 in Phase B, n=234 in Phase C), with 289 patients injected with LUM015. One 
patient enrolled in Phase B experienced blue discoloration at the injection site due to extravasation 
of LUM015 resulting from incorrect positioning of the intravenous catheter. After 92 days from 
injection, the blue discoloration disappeared but slight pallor of the skin at the injection site 
remained. One patient, with known hypersensitivity to contrast agents enrolled in the Phase C 
study experienced an anaphylaxis reaction to the LUM015 injection.  The patient recovered in <24 
hours. 
11.1 LUM015 pharmacokinetics 
During the Phase 1 IND study, the first 3 eligible subjects were dosed at 0.5mg/kg LUM015 and 
the second 3 subjects were dosed at 1.0mg/kg LUM015, with both groups injected ~29 hours prior 
to surgery. Resected tissue was imaged with the LUM Imaging Device in the pathology suite. A 
comparison of pharmacokinetic data from the initial 6 subjects to preclinical mouse studies 
suggested that a higher tumor:normal signal ratio would be achieved if tissue were imaged 4-6 
hours after injection. The next 3 subjects were injected with 1.0mg/kg of LUM015 and followed 
by 3 subjects injected with 1.5 mg/kg of LUM015 and the final cohort of 3 subjects was injected 
with 0.5mg/kg. These nine subjects were followed by surgical resection at approximately 6 hours 
after LUM015 injection (i.e. same day injection and surgery). 
To evaluate the pharmacokinetic parameters of LUM015, plasma PK samples were collected at 
the following time-points: pre-dose, 10, 20 minutes, 1, 2, 4, 8, 12, 18, 22, and 48 hours post-dose. 
The 48-hour collection was optional. Analysis of LUM015 (as Frag 1 after trypsin digestion of 
plasma) and Fragment 1 (non-digested plasma) were measured by LC-MS/MS. Additional 
metabolites, Fragment 2 and Fragment 3 were measured by HPLC-fluorescence. 
A non-compartmental approach within Win-Nonlin software was used for PK parameter 
estimation. Due to a relative complexity of the PK profile observed and data constraints inherent 
in the study (small number of patients per dose level, optional data from 22-48 hours), a 
compartmental modeling approach was not utilized. Out of the 15 subjects, the 48-h time-point 
sample was collected in 9 patients. Thus, in order to make use of the wealth of data collected up 
to 22 hours (all 15 patients from the study), but also use potentially important 48-hour data from 
the limited set of 9 subjects, PK calculations were performed on both sets (22-hour and 48-hour) 
independently. A summary of the resulting PK parameters for LUM015 are presented in Table 3. 
Table 3: Pharmacokinetic parameters for LUM015. SD = standard deviation. 
PK Parameter 
0.5 mg/kg (SD) 
mg/kg (SD) 
1.5 mg/kg (SD) 

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Tmax [hr] 
0.11 (0.17) 
0.06 (0.13) 
0.00 (0.00) 
Cmax [ug/mL] 
15.46 (2.26) 
28.41 (6.55) 
45.76 (3.78) 
AUClast [ug mL-1 h] 
78.36 (12.91) 
159.65 (45.94) 
252.08 (57.98) 
T1/2 [h] 
5.21 (1.33) 
5.08 (0.86) 
5.42 (0.67) 
 
The pharmacokinetic data support rapid clearance of LUM015. After 22 and 48 hours, only 5% 
and 2% of the parent drug remain in plasma, respectively. The PK data support a multi-phased 
profile with linear pharmacokinetics. 
11.2 Expected adverse events (associated with LUM015) 
During Phase C of the Feasibility Study, one patient had an anaphylactic reaction to the LUM015 
injection. This patient had a history of allergic reactions to contrast agents. The event was resolved 
within 24 hours of occurrence. We now consider anaphylactic reaction an expected adverse event, 
with occasional occurrence and serious severity. Table 4 below lists the expected adverse events 
due to LUM015 injection with their estimated occurrence and severity.  
Table 4: List of expected adverse events due to LUM015 administration. 
Adverse Events 
(Drug Related): 
Occurrence: 
Severity: 
LUM015 extravasation 
Occasional 
Minor 
Chromaturia 
Frequent 
Negligible 
Anaphylaxis/hypersensitivity 
Occasional 
Serious 
 
No adverse events related to the administration of LUM015 were observed during the Phase 1 IND 
safety study. Temporary blue/green discoloration of the urine was noted in these patients due to 
the blue color of LUM015. Prior to the Phase 1 study, LUM015 had not previously been used in 
humans. Lumicell’s preclinical studies demonstrated that it was reasonably safe to proceed with a 
Phase 1 IND study in humans. Preclinical studies in rats showed no LUM015 related effects on 
clinical observations, FOB evaluation, body weights, food consumption, ocular condition, clinical 
chemistry, hematology and coagulation parameters or organ weight at doses up to 53-fold higher 
than in humans. 
The results from the repeat dose toxicity study in dogs (performed by NCI) show that 
administration of 0.5 or 10.0 mg/kg of LUM015 intravenously once daily for seven consecutive 
days (8 total doses) did not cause any observable target organ toxicities. The only observable effect 
was hypersensitivity in several dogs.  
The results from a repeat dose toxicity study in rabbits show that administration of 15 mg/kg of 
LUM015 intravenously one daily for seven consecutive days was well tolerated. The test article-
related findings were limited to transient blue/green discoloration of the urine. There were no test 
article-related adverse events observed and no hypersensitivity was seen. 
Additional information is available in the Investigator’s Brochure for LUM015.  
Clinicians should be prepared for a possible hypersensitivity or allergic reaction to occur during 
each administration of LUM015. Standing orders should be in place in the event of a 
hypersensitivity or allergic reaction for immediate intervention including administration of 

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diphenhydramine, prednisone or both. If a study subject develops a Grade 3 (or greater) allergic 
reaction as defined in CTCEA 5.0, Lumicell should be contacted within 24 hours of the event: 
To Lumicell: 
Jorge Ferrer, Ph.D. 
Phone: 617-571-0592 
Email: jmferrer@lumicell.com 
Fax: 781-672-2501  
11.3 Expected adverse device effects (associated with the LUM Imaging System) 
To date in the Phase 1 and Feasibility Studies, there have been no adverse device events associated 
with use of LUM Imaging Device.  Patients in this trial will be monitored for potential infections, 
hematomas or other intraoperative or post-operative adverse device events. A list of potential 
adverse device effects is included in the Investigators Brochure. 
12 ADVERSE EVENT REPORTING REQUIREMENTS 
12.1 Definitions 
12.1.1 Adverse Event (AE) 
An adverse event (AE) is any undesirable sign, symptom or medical condition or experience that 
develops or worsens in severity after starting the first dose of study treatment or any procedure 
specified in the protocol, even if the event is not considered to be related to the study. The severity 
of any possible AE observed will be classified per the grading established by the Common 
Terminology Criteria for Adverse Events (CTCAE) 5.0. 
Abnormal laboratory values or diagnostic test results constitute adverse events only if they induce 
clinical signs or symptoms or require treatment or further diagnostic tests.  
12.1.2 Serious adverse event (SAE) 
A serious adverse event (SAE) is any adverse event, occurring at any dose and regardless of 
causality that:  
• Results in death 
• Is life-threatening. Life-threatening means that the person was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
• Requires or prolongs inpatient hospitalization (i.e., the event required at least a 24-hour 
hospitalization or prolonged a hospitalization beyond the expected length of stay). 
Hospitalization admissions and/or surgical operations scheduled to occur during the study 
period, but planned prior to study entry are not considered SAEs if the illness or disease 
existed before the person was enrolled in the trial, provided that it did not deteriorate in an 
unexpected manner during the trial (e.g., surgery performed earlier than planned). 
• Results in persistent or significant disability/incapacity. Disability is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly or birth defect; or 
• Is an important medical event when, based upon appropriate medical judgment, it may 
jeopardize the subject and require medical or surgical intervention to prevent one of the 
outcomes listed above. Examples of such medical events include allergic bronchospasm 

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requiring intensive treatment in an emergency room or at home; blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Events not considered to be serious adverse events are hospitalizations for: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition, or for elective procedures 
• elective or pre-planned treatment for a pre-existing condition that did not worsen 
• respite care 
12.1.3 Adverse device effect (ADE) 
An adverse device effect (ADE) is an adverse event which is at least possibly related to the device. 
ADEs are not considered serious adverse events. 
12.1.4 Unanticipated adverse device effects (UADEs) 
Unanticipated adverse device effect (UADE) is any serious adverse effect on health or safety or 
any life-threatening problem or death cause by or associated with, a device, if that effect, problem, 
or death was not previously identified in nature, severity, or degree of incidence in the 
investigation plan or application, or any other unanticipated serious problem associated with a 
device that relates to the rights, safety or welfare of subjects. 
12.1.5 Expectedness 
Adverse events (AEs) and adverse device effects (ADEs) can be 'Expected' or 'Unexpected'.  
12.1.5.1 Expected adverse event or adverse device effect 
Expected AEs and ADEs are those that have been previously identified as resulting from 
administration of the agent or use of the device. For the purposes of this study, an AE or ADE is 
considered expected when it appears in the current AE/ADE list, the Investigator’s Brochure, the 
Instructions For Use or is included in the informed consent document as a potential risk.   
12.1.5.2 Unexpected adverse event or adverse device effect 
For the purposes of this study, an AE or ADE is considered unexpected when it varies in nature, 
intensity or frequency from information provided in the current AE/ADE list, the Investigator’s 
Brochure, the Instructions For Use, or when it is not included in the informed consent document 
as a potential risk.   
12.1.6 Attribution 
Attribution is the relationship between an adverse event or serious adverse event and the study 
treatment. Attribution will be assigned as follows: 
• Definite – The AE or ADE is clearly related to the study treatment. 
• Probable – The AE or ADE is likely related to the study treatment. 
• Possible – The AE or ADE may be related to the study treatment.  
• Unlikely - The AE or ADE is doubtfully related to the study treatment. 
• Unrelated - The AE or ADE is clearly NOT related to the study treatment. 
Final determination of relatedness will be made by the Medical Monitor, who will integrate all 
data, including investigator’s assessment of relatedness. 

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12.2 Procedures for recording and reporting safety 
The principal investigator will assess the occurrence of AEs, SAEs, ADEs and UADEs at all 
subject evaluation time points during the study.  
All AEs, SAEs, ADEs and UADEs whether reported by the subject, discovered during questioning, 
directly observed, or detected by physical examination, laboratory test or other means, will be 
recorded in the subject’s medical record and on the appropriate study-specific case report forms.  
For events related to the imaging agent, the descriptions and grading scales found in the revised 
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for 
AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 
5.0. 
A copy of the CTCAE version 5.0 can be downloaded from the CTEP website at: 
 http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.  
12.3 Reporting requirements 
The study must be conducted in compliance with FDA regulations, local safety reporting 
requirements, and reporting requirements of the principal investigator and/or IRB. 
The Investigator will be responsible to report SAEs that occur at the Institution to the IRB in 
accordance with IRB requirements. It is the responsibility of the principal investigator to report 
serious adverse events to Lumicell and/or others as described below.  
12.4 Reporting to Lumicell 
12.4.1 Adverse Event Reporting 
Non-serious adverse events should be captured in the Case Report Form and the Adverse Event 
Log. 
All serious adverse events that occur after the initial dose of LUM015 Imaging Agent must be 
reported to Lumicell within 24 hours of becoming aware of the event. This includes events meeting 
the criteria outlined in the definitions section for SAEs. In addition to reporting the SAEs as 
outlined above, report to Lumicell adverse events that meet the following criteria within 24 hours 
of becoming aware of the event: 
• Grade 2 (moderate) and Grade 3 (severe) Events – Only events that are unexpected and 
possibly, probably or definitely related/associated with the intervention  
The principal investigator or delegated study team member must report each serious adverse event 
to Lumicell immediately after learning of the occurrence. In the event that the Investigator does 
not become aware of the serious adverse event immediately (e.g., subject sought treatment 
elsewhere), the principal investigator is to report the event immediately after learning of it and 
document the time of his or her first awareness of the adverse event. Report serious adverse events 
in writing to Lumicell according to the protocol training guidelines and: 
 
 
To Lumicell:  
 
 
 
Jorge Ferrer, Ph.D. 
Phone: 617-571-0592 
Email: jmferrer@lumicell.com  

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Fax: 781-672-2501 
 
The Case Report Form (CRF) for a Serious Adverse Event should be completed as soon as possible 
after notifying Lumicell of the event.  Written notification to Lumicell is required as indicated 
above in addition to the completion of the SAE CRF. 
12.4.2 Unanticipated Adverse Device Effects 
All unanticipated adverse device effects (UADEs) that occur during the study must be reported to 
Lumicell using the provided SAE form. 
The principal investigator must report each unanticipated adverse device effect to Lumicell as soon 
as possible, but in no event later than 10 working days after the Investigator learning of the 
occurrence. Investigators should document their initial knowledge of the event. Report 
unanticipated adverse device in writing to Lumicell according to protocol training guidelines and: 
To Lumicell: 
Jorge Ferrer, Ph.D. 
Phone: 617-571-0592 
Email: jmferrer@lumicell.com  
Fax: 781-672-2501 
The Case Report Form (CRF) for a UADE should be completed as soon as possible after notifying 
Lumicell of the event. Written notification to Lumicell is required as indicated above in addition 
to the completion of the SAE CRF. 
Lumicell will immediately conduct an evaluation of a UADE and must report the results of the 
evaluation to FDA, all reviewing IRBs, and participating investigators within 10 working days 
after the sponsor first receives notice of the effect. This evaluation will determine any action 
needed as described in section 8.6 of this protocol. 
12.4.3 Non-Serious Adverse Event and Adverse Device Effect Reporting  
Non-serious adverse events and non-serious adverse device effects will be reported to Lumicell on 
the adverse events Case Report Forms.   
12.5 Reporting to the Institutional Review Board (IRB) 
The investigative site will report adverse events, serious adverse events, adverse device effects and 
unexpected adverse device effects directly to the IRB in accordance with the institution’s or 
Central IRB policy. 
12.6 Reporting to the Food and Drug Administration (FDA) 
Lumicell or its agents will report to the FDA via their IDE as required in 21 CFR Parts 312 & 812 
and as additionally described in this protocol. 
 
 
12.7 Reporting to Hospital Risk Management 
The principal investigator will report to their local Risk Management office any subject safety 
reports or sentinel events that require reporting according to institutional policy. 
12.8 Monitoring of adverse events/adverse device effects and period of observation 
All adverse events and adverse device effects, both serious and non-serious, and deaths that are 
encountered from initiation of study intervention and throughout the study, should be followed to 

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their resolution, or until the principal investigator assesses them as stable, or the principal 
investigator determines the event to be irreversible, or the subject is lost to follow-up. The presence 
and resolution of AEs, ADEs, SAEs and UADEs (with dates) should be documented on the 
appropriate case report form and recorded in the subject’s medical record to facilitate source data 
verification.  
For some SAEs/UADEs, the investigator, Sponsor, or designee may follow-up by telephone, fax, 
and/or monitoring visit to obtain additional case details deemed necessary to appropriately 
evaluate the SAE/UADE report (e.g., hospital discharge summary, consultant report, or autopsy 
report).  
Subjects should be instructed to report any serious post-study event(s) that might reasonably be 
related to participation in this study. The principal investigator should notify Lumicell and the IRB 
of any unanticipated death or adverse event occurring after a subject has discontinued or terminated 
study participation that may reasonably be related to the study.   
12.9 Protocol deviations 
Protocol deviations to ongoing studies are any unapproved changes in the study design and/or 
procedures that are within the Investigator’s control and not in accordance with the IRB approved 
protocol. The Principal Investigator or designee will enter all protocol deviations on the Protocol 
Deviation Tracking Log provided by Lumicell. The log will be reviewed and updated as necessary 
by the site team. The site monitor (CRA) will review the log during their interim monitoring visit 
and obtain a copy of the log for Lumicell files. Additionally, the site should inform the IRB of 
record of the protocol deviation following the IRB’s policy on reporting deviations.  
13 DATA AND SAFETY MONITORING 
13.1 Data reporting 
13.1.1 Method  
Lumicell will collect, manage, and monitor data for this study.  
13.1.2 Data submission  
It is the expectation that all CRFs will be completed in a contemporaneous manner to the time of 
study related procedures. Timely completion of the reports will allow Lumicell to monitor the 
study conduct and data in an effective manner.  
13.2 Safety review 
A Medical Monitor will review and monitor adverse events data from this trial. The Medical 
Monitor will be a medical doctor with experience in oncology and who has no direct relationship with 
the study. Information that raises any questions about subject safety will be addressed with the 
Principal Investigator and study team. 
13.3 Monitoring  
Lumicell will conduct a study assessment followed by a site initiation visit (either face to face, or 
via web) in which the site team will receive protocol specific training in addition to a review of all 
investigator responsibilities, and expectations of Lumicell. Throughout the conduct of the study 
Lumicell will conduct intermittent site visits to assure compliance with the protocol and all 
applicable regulations. During these visits, there will be a source data verification of critical data 

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points transcribed to the CRF. Data monitoring may also be conducted via central and remote 
monitoring. At study completion, Lumicell will conduct a study closure visit. This study visit will 
assure that all site regulatory documentation is present and updated; all data queries are resolved; 
investigator sign-off/approval of all applicable study data submitted to Lumicell has occurred; and 
all final disposition instructions from Lumicell have been delivered to the site investigator. 
Involvement in this study as a participating investigator implies acceptance of the approved 
protocol, the potential for audits or inspections, including source data verification, by 
representatives of the FDA, Lumicell (or their affiliates), the institutional review board, or their 
representatives. The purpose of these audits or inspections is to examine study-related activities 
and documents to determine whether these activities were conducted and data were recorded, 
analyzed, and accurately reported in accordance with the protocol, institutional policy, Good 
Clinical Practices (GCPs), and any applicable regulatory requirements. 
All data will be monitored for timeliness of submission, completeness, accuracy, and adherence to 
protocol requirements.  
13.4 Data Safety Monitoring Board 
An independent Data Safety Monitoring Board (DSMB) will be established to review the safety 
of the LUM Imaging System and to review any SAEs that occur during the study. The DSMB will 
develop and follow a DSMB Charter. The DSMB will be composed of at least 2 oncology 
specialists (at least one of whom specializes in surgical oncology) and a statistician. The DSMB 
will be provided with all reports of adverse events including SAEs regardless of investigator 
causality assessments. 
Following the initial meeting, DSMB meetings will occur on a periodic basis in accordance with the 
DSMB charter. The chairperson of the DSMB will also be immediately provided with the report of 
any SAE that is judged as possibly, probably, or definitely attributable to treatment with the 
investigational product. The charter of the DSMB will specify that this committee is charged with 
providing periodic reports to Lumicell that contain recommendations that include, but are not limited 
to, (a) continuation of the study, and (b) termination of the study. 
14 REGULATORY CONSIDERATIONS 
14.1 Protocol review and amendments 
This protocol, the proposed informed consent and all forms of subject information related to the 
study (e.g., advertisements used to recruit subjects) and any other necessary documents must be 
submitted, reviewed and approved by a properly constituted IRB governing each study location.  
Any changes made to the protocol must be mutually agreed upon by Lumicell. Such changes must 
be submitted as amendments and must be approved by the IRB prior to implementation. Any 
changes in study conduct must be reported to the IRB. Lumicell will disseminate protocol 
amendment information to all participating investigators.  
All decisions of the IRB concerning the conduct of the study must be made in writing. 
In addition, any modifications to the protocol, consent or case report forms will be submitted to 
the FDA. 
14.2 Informed consent 

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All subjects must be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study. The 
formal consent of a subject, using the current IRB approved consent form, must be obtained before 
any study-related procedures are performed. The consent form must be signed and dated by the 
subject or the subject’s legally authorized representative, and by the person obtaining the consent. 
The subject must be given a copy of the signed and dated consent document. The original signed 
copy of the consent document must be retained in the medical record or research file.  
14.3 Ethics and Good Clinical Practice (GCP) 
This study is to be conducted according to the following considerations, which represent good and 
sound research practice: 
• E6 Good Clinical Practice: Consolidated Guidance  
• US Code of Federal Regulations (CFR) governing clinical study conduct and ethical 
principles that have their origin in the Declaration of Helsinki 
o Title 21 Part 11 – Electronic Records; Electronic Signatures  
o Title 21 Part 50 – Protection of Human Subjects  
o Title 21 Part 54 – Financial Disclosure by Clinical Investigators  
o Title 21 Part 56 – Institutional Review Boards  
o Title 21 Part 812 – Investigational Device Exemptions  
• State laws 
• Institutional research policies and procedures 
• Contractual agreements 
It is understood that deviations from the protocol should be avoided, except when necessary to 
eliminate an immediate hazard to a research subject. In such case, the deviation must be reported 
to the IRB according to the local reporting policy. 
14.4 Study documentation 
The investigator and all designees must prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each research subject. 
This information enables the study to be fully documented and the study data to be subsequently 
verified. 
Original source documents supporting entries in the case report forms include but are not limited 
to hospital records, clinical charts, laboratory and pharmacy records, recorded data from automated 
instruments, microfiches, photographic negatives, microfilm or magnetic media, and/or x-rays.  
14.4.1 Study Documentation Practices 
a) The investigator must maintain adequate records to enable the conduct of the study to 
be fully documented 
b) All records, including electronic forms, must be filled out completely.   Complete each 
space or blank. If there is no information to go into a space or blank, then use the symbol 
“N/A”.  If an entire section or page of a record is “N/A”, it is acceptable to indicate this by 
drawing one line through the entire section/page and use “N/A” near that line.  It is 
acceptable to check a box marked “N/A” to indicate that a section or an entire page is not 
applicable. The use of ‘White-Out’ or similar correction fluid is forbidden. 

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c) Use of highlighters on records is acceptable so long as the highlighter color does not 
obscure the underlying text if the record is copied. 
d) Accuracy is required.  Always verify entries are correct and consistent with other 
information. 
e) Signatures are to be authentic. 
f) Recorded dates are to be the actual dates in which the activities were recorded.      Back-
dating is forbidden. 
g) If drinks or chemicals are spilled on original records, dry them off to the best of your 
ability, make an immediate photocopy and make a notation of the event on the copy. Retain 
the original record except in the event of contamination with a hazardous material. 
h) All forms must be filled out using non-erasable pen and must be legible.  The use of blue 
or black ink is preferred. 
i) Errors must be crossed out with a single line, the correction inserted, and the change 
initialed and dated by the approved person making the correction.  The reason for the 
correction must be stated. 
14.5 Records retention 
All study-related documents must be retained for the maximum period required by applicable 
federal regulations and guidelines, institutional policies or contractual agreement between 
Lumicell and the participating institution. 
15 STATISTICAL CONSIDERATIONS  
A full description of the data analysis is included in the Statistical Analysis Plan. 
15.1 Analysis Populations 
• Safety (SAF) Population: the safety population includes all subjects who received study 
drug (LUM015). 
• Modified Intent To Treat (mITT) population: includes the subjects in SAF, but excluding 
subjects who are not able to be imaged with the LUM Imaging System. The mITT 
population will be used as the primary analysis population for the three co-primary efficacy 
endpoints and efficacy analysis of the secondary endpoints.  
• Per-Protocol Population: Includes mITT subjects who complete all study evaluations and 
are without any major protocol deviations that may impact data collection or efficacy 
analysis. A sensitivity analysis of the primary and secondary efficacy endpoints will be 
conducted using the per-protocol analysis set. 
15.2 Definition of truth standard for diagnostic performance evaluation (sensitivity and 
specificity) 
We propose to use a hierarchical approach to determine the truth standard as therapeutic shaves 
were taken only when the LUM imaging system signaled positive for potential residual tumor. The 
highest truth standard is whether pathology finds cancer in a tissue shave removed from the area 
that was imaged in the cavity. When a shave does not exist, then whether tumor is found in a re-
excision surgery is considered as the truth standard. When neither a shave nor a second surgery 
exists for a given orientation that was imaged, the margin assessment of that orientation is used as 
truth standard. Error! Reference source not found. shows a schematic for determination of the 
truth standard. 

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Figure 6: Definition of truth standard to evaluate the LUM Imaging System diagnostic performance. 
When the therapeutic shave is not available and the follow-up surgery is performed, only the 
pathology from the first-time re-excision at the tissue/orientation level will be used for hierarchical 
sensitivity/specificity evaluation. 
The orientation of the tissue removed during a re-excision is typically noted in the pathology report 
and matches the orientation in which a positive margin was identified from the initial surgery. 
However, there will be instances in which the orientation of the tissue removed during a re-excision 
is not specified. In the cases of unclear orientation of the tissue removed during the re-excisions, 
the orientations with positive margins will be used as positive/negative with cancer as suggested 
by the pathology of the resected tissue 
If a mastectomy is performed as a follow-up surgery and no cancer found in the mastectomy 
specimen, all the orientation will be considered as cancer negative for truth standard. If 
mastectomy is performed and cancer is found and no indication of orientations where cancer has 
been found, the orientation in which a positive margin was identified in the initial lumpectomy 
will be considered as cancer positive for truth standard unless otherwise noted. 
When a therapeutic shave and re-excision are not available for an orientation, the prior margin of 
the resected tissue of the corresponding orientation will be used as ground inferred truth for 
evaluation. 
Refer to the associated Statistical Analysis Plan (SAP) for additional details. 
15.3 Sample Size 
The pivotal study will be powered based upon targeting success for the three co-primary endpoints. 
The efficacy endpoints will be assessed in the patients who undergo LUM imaging (not the 1/10th 
of subjects randomized to the control arm). 
15.3.1 Residual cancer removal 

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The null hypothesis is that the true percentage of patients in whom at least one LUM-guided shave 
removed after the SOC procedure contain cancer as confirmed by pathology examination is smaller 
or equal than 3%: 
𝐻𝐻0: 𝑝𝑝≤3% 
The alternative hypothesis is that the true percentage of patients in whom at least one LUM-guided 
shave removed after the SOC procedure contain cancer as confirmed by pathology examination is 
larger than 3%: 
𝐻𝐻𝐴𝐴: 𝑝𝑝> 3% 
where p is the true percentage of patients in whom at least one therapeutic shave removed after the 
SOC procedure contain cancer as confirmed by pathology examination.  
The hypothesis will be tested using an exact Binomial test at a one-sided significance level of 
2.5%. The true proportion 𝑝𝑝 will be estimated along with a one-sided 97.5% exact confidence 
interval. 
Lower bound selection for removal of residual cancer endpoint 
To choose the success criteria for the proportion of patients who have residual cancer found in at 
least one LUM-guided shave, we used published results for estimates of local recurrence before 
and after adjuvant radiation, assuming that most local recurrences are a consequence of unresected 
cancer during the initial surgery. The meta-analysis conducted on approximately 28,000 patients 
to support the consensus guideline for margin in 2014 from SSO-ASTRO, reported an overall 
recurrence rate of 5.3% for patients undergoing lumpectomy and receiving whole breast radiation 
therapy (including patients with positive and negative margins) [1]. Other investigators have 
published local recurrence rates for patients with negative margins at 10.2% without a radiation 
boost, while 6.2% for those with radiation boosts [2]. Based on this data, we estimate that radiation 
addresses approximately 50% of residual cancer, but not all. Our Phase C results shows a 
proportion of 26/230 or 11.3% [95% CI: 7.5%-16.1%], supporting the lower bound selection of 
this endpoint. 
Sample size for residual cancer removal 
Our preliminary analysis of the Phase C exploratory data indicated that LUM detected residual 
cavity cancer in 11% of patients (26/230). To power the study, we are using a slightly more 
conservative assumption of a ~9% true percentage of patients in whom at least one therapeutic 
shave has cancer confirmed by pathology. With this assumption, enrolling 220 evaluable subjects, 
a binomial exact test for proportions at a 1-sided significance level of 2.5%, will have 90% power 
to declare the percentage of patients in whom at least one therapeutic shave has cancer confirmed 
by pathology to be larger than 3%. 
15.3.2 Sensitivity and specificity 
The verification of the sensitivity and specificity co-primary endpoints will be a refutation of the 
null hypotheses 
𝐻𝐻01
𝑠𝑠: 𝑠𝑠𝑠𝑠𝑠𝑠 ≤ 40% against the alternative 𝐻𝐻11
𝑠𝑠: 𝑠𝑠𝑠𝑠𝑠𝑠 >  40% 
𝐻𝐻02
𝑠𝑠: 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 ≤ 60% against the alternative 𝐻𝐻12
𝑠𝑠: 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 >  60% 

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where 𝑠𝑠𝑠𝑠𝑠𝑠 and 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 represent the true sensitivity and specificity, respectively. These hypotheses 
will be tested using an exact binomial test for testing proportions in those with a positive ground 
truth result (sensitivity) and those with a negative ground truth result. 
Lower bound selection for sensitivity and specificity endpoints 
Data from the Phase C Feasibility Study showed pathology margin assessment sensitivity to 
predict cancer in the cavity of ~40%. However, this pathology assessment is done several days 
after the surgery and can lead to second surgeries. Because the LUM Imaging System provides the 
additional benefit of assessing the cavity in real-time, a lower bound for instrument sensitivity > 
40% is proposed as the success criterion for this hypothesis-tested endpoint. We expect the 
sensitivity to be similar to that observed in the Phase C study of 67% [95% CI: 56%-79%]. 
The Phase C data shows that at the current specificity performance of 70% [95% CI: 68%-73%], 
an average of 1.1 additional shaves were removed guided by the LUM Imaging system, accounting 
for ~10% of all the total resected tissue. We selected a lower bound for specificity of 60% to ensure 
that similar performance in the pivotal trial is obtain regarding tissue removal. Also, with this 
lower bound, a Youden Index > 0 will be demonstrated to indicate non-random diagnostic 
performance. 
Sample size for sensitivity 
Assuming a sensitivity of 60%, obtaining 70 truth standard positive events, a binomial exact test 
for proportions at a 1-sided significance level of 2.5%, will have 90% power to declare the lower 
bound of sensitivity > 40%. 
Sample size for specificity 
Assuming a specificity of 65%, obtaining 1021 truth standard negative events, a binomial exact 
test for proportions at a 1-sided significance level of 2.5%, will have 90% power to declare the 
lower bound of specificity > 60%. 
15.3.3 Study sample size, event-driven design, and overall study power 
The pivotal study is powered based upon targeting success for the three co-primary endpoints as 
outlined above. The efficacy endpoints will be assessed in the patients who undergo LUM-guided 
imaging (not the 1/10th of subjects randomized to the control arm). 
Based on Phase C data, it is expected that 268 patients will provide the necessary 70 truth standard 
positive events to power for sensitivity. Also, based on Phase C data, it is expected that 152 patients 
will provide the necessary 1021truth standard negative events to power for specificity. To power 
for the removal of residual cancer endpoint, approximately 220 patients are required. Thus, the 
size of this study is driven by the necessary number of truth standard positive events. 
Adding 15% to the sample size of 268 patients to include subjects in the control arm and some 
expected data loss, it is estimated that 310 total patients will be needed for the pivotal study. 
However, given the uncertainty of translating the number of truth standard positive events to actual 
number of patients, the pivotal trial is planned as an event-driven clinical study. Patients will be 
enrolled until 70 truth standard positive events are reported, up to a maximum of 350 patients. The 
number of truth standard positive events will be counted based on the truth standard hierarchical 
approach from Figure 6. Counting of these events will be conducted via software programming to 
read from the electronic data capture system; no endpoints will be calculated at that time. Results 

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from the event counting process will be accessible to the DSMB which will then inform Lumicell 
personnel on whether the targeted number of events has been reached or if enrollment needs to 
continue. 
At this sample size, the power for the sensitivity endpoint is 90%, for specificity is 99% and for 
removal of residual cancer is 96%. Thus, the overall study power is 90% x 99% x 96% = 86%. 
Revision note: As of the release of revision 08 of study protocol CL0007, an event count 
conducted in April 1st, 2021 indicated that 380 patients need to be enrolled to achieve the necessary 
70 truth standard positive events. We now intend to enroll up to 450 subjects in this study. 
15.3.4 Overall Primary Hypotheses 
The overall primary hypotheses for the primary endpoints is 
𝐻𝐻0
𝑝𝑝 (null): 𝐻𝐻0or 𝐻𝐻01
𝑠𝑠 or 𝐻𝐻02
𝑠𝑠   versus  𝐻𝐻1
𝑝𝑝 (alternative): 𝐻𝐻1 and 𝐻𝐻11
𝑠𝑠 and 𝐻𝐻12
𝑠𝑠 
The removal of residual cancer endpoint will be tested at a one-sided significance level of 2.5%. 
Sensitivity and specificity endpoints will be tested at a two-sided significance level of 5%. 
15.4 Statistical Methods 
15.4.1 General considerations 
All analyses will be performed under Good Clinical Practice (GCP) standards using a prespecified 
statistical analysis plan (SAP). All analyses will be conducted and tables and listings generated 
using Statistical Analysis System (SAS®) Version 9.4 or higher. Graphics may be prepared with 
SAS Version 9.4 or higher; R version 3.1.2 or higher (R Core Team (2014)), SigmaPlot 12.3 or 
higher (Systat Software, Inc., San Jose, California). 
15.4.2 Demographic and baseline characteristics 
Demographic and baseline characteristic including: age, race and ethnicity, menopausal status, 
mammographic breast density, palpability, cancer histologic type, tumor size, node positive 
patients, and tumor receptor status (ER/PR/HER2), and baseline body mass index (BMI) 
calculated from weight and height will be summarized for the study sample. Statistics for 
continuous variables will include mean, median, standard deviation (SD), minimum, maximum 
and sample size for the overall sample and for subgroups, and two-sided 95% CI of the mean 
difference between (control and study arms) and subgroups. Binary variables will be described 
with frequencies and percentages for the overall sample.  Demographic and baseline characteristics 
will be summarized by overall using descriptive statistics for analysis populations. 
15.4.3 Efficacy analyses 
Three co-primary endpoints 
• Ratio of patients who have residual cancer found in at least one Lumicell-guided shave 
(also known as therapeutic shave) among all patients randomized to the device arm. 
• Diagnostic performance of instruments measured two separate endpoints as sensitivity and 
specificity in a per-tissue basis. 
Secondary endpoints  

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a. Proportion of patients with positive margins after standard of care breast-conserving 
surgery who have a LUM Imaging System signal in the cavity above the threshold as 
defined by the tumor detection algorithm (i.e., a positive LUM signal). 
b. Proportion of subjects with pathology-positive margins after standard of care breast-
conserving surgery for whom additional LUM Imaging System-guided shaves resulted in 
pathology-negative margins among patients with positive margins. Note: This endpoint 
also estimates the potential reduction in re-excision surgeries following standard of care 
breast-conserving surgery that resulted from a positive SOC margin. 
c. Proportion of subjects with pathology-positive margins after standard of care breast-
conserving surgery for whom additional LUM Imaging System-guided shaves resulted in 
pathology-negative margins among all patients. 
d. Ratio of patients with negative margins after the SOC procedure who have residual cancer 
found in at least one Lumicell-guided (or therapeutic) shave among patients with negative 
margins. 
e. Ratio of patients with negative margins after the SOC procedure who have residual cancer 
found in at least one Lumicell-guided (or therapeutic) shave among all patients 
f. Mean and median incremental volume (in cubic centimeters) of tissue removed from 
therapeutic shaves: For each patient, absolute shave volume will be calculated as length (c) 
× width (c) × depth (c) for each therapeutic shave with the sum by patient of all therapeutic 
shaves. Subjects with no therapeutic shaves taken will have a therapeutic shave volume of 
0cc. 
g. Mean and median contribution of therapeutic shave volume to total tissue removed. 
h. Comparison of adverse events in subjects that have at least one therapeutic shave versus 
subjects that have no therapeutic shaves. 
i. Average number of therapeutic shaves taken per subject overall and by type of SOC 
lumpectomy procedure (i.e., lumpectomy with comprehensive shaves vs. lumpectomy with 
or without selective shaves). 
j. Percent of device failures that led to failure of using the LUM Imaging System to capture 
data. 
k. Rate of re-excision procedures as a result of a positive margin status following SOC 
(control arm) and LUM Imaging procedures (device arm). 
l. Number of re-excisions for each patient 
m. Number of re-excisions recommended 
n. Collect exploratory data on tissue types found in therapeutic shaves. 
o. Collect exploratory data on patient reported outcomes. 
p. Adverse events stratified by severity and relatedness to drug/device. 
q. Serious adverse events stratified by severity and relatedness to drug/device. 
r. Adverse events by preferred term (sorted by descending occurrences for each preferred 
term). 
s. Summary of adverse events, overall and split by expectedness to drug/device 
15.4.4 Safety analyses 
Safety data will be reported as: 
• Adverse events stratified by severity and relatedness to drug/device. 
• Serious adverse events stratified by severity and relatedness to drug/device. 

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• Adverse events coded per MedDRA guidelines 
• Adverse events by preferred term per MedDRA (sorted by descending occurrences for each 
preferred term). 
All adverse events will be evaluated and assigned the “expectedness” by a Lumicell representative 
as described in the study plans or protocols and will be reported accordingly. 
Two safety analyses sets will be completed: one for all the patients injected with LUM015 across 
all the Lumicell clinical studies (see Error! Reference source not found. in the Statistical 
Analysis Plan document), and another one for just the breast cancer patients. 
15.4.5 Exploratory Data Analyses 
Patient reported outcome measures (PROMs) will be reported as an exploratory endpoint. Also, 
the type of tissue found in therapeutic shaves will be reported as an exploratory endpoint. 
In this protocol, the definition of positive margins is described in section Error! Reference source 
not found.. In addition, Lumicell will collect margin distance information such that alternative 
definitions (e.g. DICS on ink) can be tested in an exploratory manner. 
15.4.6 Missing or spurious data 
During Lumicell-guided imaging, when there is not enough tissue to be removed (e.g. too close to 
skin or too close to the chest wall) no LUM image shall be recorded because it does not generate 
an actionable result. 
In the case where the LUM Imaging System indicates that a therapeutic shave needs to be removed 
but the surgeon decides not to follow this guidance, the reason for not doing so will be recorded in 
the patient’s CRF or during imaging. These instances are considered as a protocol deviation. There 
are other cases when the shavings reach protocol limits so no shaving will be performed. In these 
cases, the data will be included in the performance evaluation as is - that is no Lum-guided shave-
taken will be considered as no removing of cancer or positive margin. However, they will be 
considered as a detection if there are cancer in the re-excision or if there are positive margins on 
the corresponding orientations.  
In occasions, a cavity image may be recorded from an unintended region or the image may be 
deemed as low quality (blurry, out of focus, etc.). For example, the surgeon realizes that he/she 
placed the device in the wrong location within the cavity after recording an image. Since the LUM 
software does not allow to overwrite saved images, this situation will be documented, the image 
will be excluded from the analysis. 
16 PUBLICATION PLAN 
The results of this study will be made public within 12 months of the completion of the study. 
Reference the Clinical Trial Agreement for detailed publication policy information.  
17 REFERENCES 
1. 
Moran, M.S., et al., Society of Surgical Oncology-American Society for Radiation 
Oncology consensus guideline on margins for breast-conserving surgery with whole-
breast irradiation in stages I and II invasive breast cancer. Int J Radiat Oncol Biol Phys, 
2014. 88(3): p. 553-64. 

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2. 
Morrow, M., et al., Society of Surgical Oncology-American Society for Radiation 
Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for 
Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ. J 
Clin Oncol, 2016. 
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Kreike, B., et al., Continuing risk of ipsilateral breast relapse after breast-conserving 
therapy at long-term follow-up. Int J Radiat Oncol Biol Phys, 2008. 71(4): p. 1014-21. 
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Singletary, S.E., Surgical margins in patients with early-stage breast cancer treated with 
breast conservation therapy. Am J Surg, 2002. 184(5): p. 383-93. 
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Smitt, M.C., et al., Predictors of reexcision findings and recurrence after breast 
conservation. Int J Radiat Oncol Biol Phys, 2003. 57(4): p. 979-85. 
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Dillon, M.F., et al., A pathologic assessment of adequate margin status in breast-
conserving therapy. Ann Surg Oncol, 2006. 13(3): p. 333-9. 
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Kurniawan, E.D., et al., Predictors of surgical margin status in breast-conserving surgery 
within a breast screening program. Ann Surg Oncol, 2008. 15(9): p. 2542-9. 
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Schiller, D.E., et al., Factors associated with negative margins of lumpectomy specimen: 
potential use in selecting patients for intraoperative radiotherapy. Ann Surg Oncol, 2008. 
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Smitt, M.C. and K. Horst, Association of clinical and pathologic variables with 
lumpectomy surgical margin status after preoperative diagnosis or excisional biopsy of 
invasive breast cancer. Ann Surg Oncol, 2007. 14(3): p. 1040-4. 
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Waljee, J.F., et al., Predictors of re-excision among women undergoing breast-conserving 
surgery for cancer. Ann Surg Oncol, 2008. 15(5): p. 1297-303. 
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and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-
2018.pdf. 
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Chagpar, A.B., Cavity Shave Margins in Breast Cancer. N Engl J Med, 2015. 373(22): p. 
2187-8. 
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Coopey, S.B., et al., Lumpectomy cavity shaved margins do not impact re-excision rates in 
breast cancer patients. Ann Surg Oncol, 2011. 18(11): p. 3036-40. 
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Weissleder, R. and U. Mahmood, Molecular imaging. Radiology, 2001. 219(2): p. 316-33. 
15. 
Mohamed, M.M. and B.F. Sloane, Cysteine cathepsins: multifunctional enzymes in cancer. 
Nat Rev Cancer, 2006. 6(10): p. 764-75. 
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Gocheva, V. and J.A. Joyce, Cysteine cathepsins and the cutting edge of cancer invasion. 
Cell Cycle, 2007. 6(1): p. 60-4. 
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Joyce, J.A., et al., Cathepsin cysteine proteases are effectors of invasive growth and 
angiogenesis during multistage tumorigenesis. Cancer Cell, 2004. 5(5): p. 443-53. 
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Gocheva, V., et al., IL-4 induces cathepsin protease activity in tumor-associated 
macrophages to promote cancer growth and invasion. Genes Dev, 2010. 24(3): p. 241-55. 
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Jaffer, F.A., et al., Optical visualization of cathepsin K activity in atherosclerosis with a 
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Chen, B. and M.O. Platt, Multiplex Zymography Captures Stage-specific Activity Profiles 
of Cathepsins K, L, and S in Human Breast, Lung, and Cervical Cancer. J Transl Med, 
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Lecaille, F., J. Kaleta, and D. Bromme, Human and parasitic papain-like cysteine 
proteases: their role in physiology and pathology and recent developments in inhibitor 
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22. 
Naidu, R., et al., Expression of c-erbB3 protein in primary breast carcinomas. Br J Cancer, 
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Thomssen, C., et al., Prognostic value of the cysteine proteases cathepsins B and cathepsin 
L in human breast cancer. Clin Cancer Res, 1995. 1(7): p. 741-6. 
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Lerebours, F., I. Bieche, and R. Lidereau, Update on inflammatory breast cancer. Breast 
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18 APPENDICES 
 
 
 

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Appendix A:  Method for removing, orienting, inking and naming the main specimen and shaved 
cavity margins.  
The methods described below are adapted from Cabioglu, et al. (ASO 14:1458-1471; 2007). This 
method applies to both palpable and non-palpable breast masses. 
As described below, stitching of the main specimen (#2) and protocol specified nomenclature of 
the resected specimen (Appendix B) are protocol requirements to support data integrity.  Non-
compliance with these elements will be considered protocol deviations. Inking of the specimen 
and shaves, and stitching of the shaves are recommended per protocol but non-compliance is not 
considered a protocol deviation if the process negatively interferes with the institution’s standard 
procedure.   
Procedure: 
1. Surgeon performs surgery attempting to obtain grossly negative margins in the main 
specimen. 
2. Surgeon places orientation stitches at the superior and lateral orientations of the main 
specimen immediately after it is removed from the patient. It is extremely important 
to maintain the orientation of the specimen relative to the lumpectomy cavity to 
be able to correlate LUM images of the cavity with pathology examination of the 
main specimen. 
3. Surgeon inks all surfaces of the main specimen using a differently colored ink for 
each orientation. Lumicell will provide an inking kit to facilitate this process. This kit 
is not part of the LUM Imaging System. 
4. Surgeon may elect to remove additional tissue shaves based on palpation of the 
specimen or lumpectomy cavity walls, x-ray imaging of the main specimen (mainly 
for non-palpable masses), visual inspection, intraoperative frozen sections, standard 
of care shaves, or comprehensive shaves. If additional shaves are removed, the shaves 
must be labeled according to the orientation it was removed from and the number of 
additional tissue shaves taken from that orientation (see Appendix B for naming 
convention of resected tissue). For example, the first additional tissue from the medial 
orientation should be named as “medial 1”. 
5. If additional shaves are removed, the surgeon should ink as many surfaces as possible 
maintaining the same color used for a given orientation in the main specimen. For 
example, if the superior orientation of the main specimen is inked yellow, then the 
margin side of a tissue from the superior orientation should be inked yellow. 
6. When any additional shaves are removed, the margin side should be marked with a 
stitch and should be inked per institution’s standard procedure.

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Appendix B: Guidelines for naming of resected tissues  
Two (2) standard naming conventions, described as “Naming Convention B1” and “Naming Convention B2” in Table B below, shall 
be used by all sites to blind pathologists to whether the shave was excised during standard of care or Lumicell guidance.  As the shaves 
are removed during the surgery, a record will be created in the operating room by the study personnel to indicate whether the tissue was 
excised during standard of care or Lumicell guidance (according to column B1).  The pathologists must not have access to the record 
using naming convention B1 until after the pathology assessment has been recorded. The samples shall be labeled according to Naming 
Convention B2 before transfer from the operating room to pathology, and this naming convention shall follow the samples through the 
final pathology report. 
Table B: Guidelines for naming resected tissues  
Tissue 
Naming convention B1 
Unblinded source for 
specimen orientation, 
shave number, and 
type of shave 
Naming example for 
surgical record and study 
source document (B1) 
Naming convention B2 
Blinded naming 
convention for 
pathology 
Naming example for 
specimen to be sent to 
pathology (B2) 
Main specimen 
Main specimen [side of 
breast] 
Main specimen, left 
breast 
Main specimen [side of 
breast] 
Main specimen, left 
breast 
Standard of care 
shaves 
 
[Orientation] [sequential 
shave number for an 
orientation] SOC 
Superior 1 SOC  
[Orientation] [sequential 
shave number for an 
orientation]  
Superior 1 
Therapeutic 
shaves 
[Orientation] [sequential 
shave number for an 
orientation] Therapeutic 
Medial 1 Therapeutic 
 
Medial 2 Therapeutic 
 
Superior 2 Therapeutic* 
[Orientation] [sequential 
shave number for an 
orientation]  
Medial 1 
 
Medial 2 
 
Superior 2 * 
*Note this shave is named as “2” because a SOC shave was obtained in the same orientation. This allows for final margin status 
to be known when the specimen is blinded to type of shave for pathology evaluation.  

Pivotal study of intraoperative imaging in breast cancer 
CL0007r08 
07APR2021 
 
 
 
LUMICELL CONFIDENTIAL 
This document is confidential. Do not disclose or use except as authorized. 
46 
 
 
Appendix C: Handling and sectioning SOC and therapeutic shaves 
All cavity shaves, whether an SOC or therapeutic, will be handled and processed in the same 
manner as described below. 
1. Section the shave in its entirety perpendicular to its long axis at approximately every 2 mm. 
2. Place each section of a shave in a cassette for paraffin embedding. Note: if the sections are 
small enough, more than one section can be placed in a single cassette. 
3. Prepare a paraffin embedded block from each cassette (e.g., if there are three cassettes for 
a single shave, this should result in three different blocks). 
4. Prepare at least one histopathology slide for margin assessment from every single block. 
5. Determine the margin status for each histopathology slide from a shave and record results. 
6. Report results using naming convention B2, as described in Appendix B. 
 
Example: 6 total shaves are removed from a patient and sectioning of the shaves generates 3 blocks 
each. The total number of slides for margin assessment would be: 6 shaves x 3 blocks/shave = 18 
total slides from shaves. 
 
 

Pivotal study of intraoperative imaging in breast cancer 
CL0007r08 
07APR2021 
 
 
 
LUMICELL CONFIDENTIAL 
This document is confidential. Do not disclose or use except as authorized. 
47 
 
 
Appendix D:  Confidentiality and Confirmation Signatures (Protocol Signature Page) 
 
Confidentiality agreement: 
 
 
The Principal Investigator agrees to handle all information and documentation received from 
Lumicell, Inc. under the terms of the study agreement as well as the work performed and the 
results obtained during the duration and after termination of the agreement confidentially. 
Accordingly, all separate publications and lectures with any reference to the object of this 
agreement need the previous written consent of Lumicell, Inc. The evaluator ensures that all 
other persons involved in this project will maintain confidentiality as well. 
 
 
Confirmation of the Principal Investigator: 
 
 
Herewith I/we confirm to have understood and accepted all elements of the study protocol 
and the experimental part as agreed upon. 
 
 
 
 
 
 
Location/Institution 
 
Date 
 
 
 
 
 
 
Signature of Principal Investigator (PI) 
 
Printed name of PI