Single Dose Investigator Initiated Pilot Study to Investigate CYTALUX (Pafolacianine) for Intraoperative Imaging of Patients With Endometrial Cancer Planned for Surgery
Phase: EARLY_PHASE1
Conditions: Endometrial Cancer, Near Infrared Fluorescence Imaging, CYTALUX (Pafolacianine) Injection, Planned Diagnostic Laparoscopies
Sponsor: Abramson Cancer Center at Penn Medicine

 
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CONFIDENTIALITY STATEMENT 
The information contained within this document is confidential and may not be used, divulged, published, 
or otherwise disclosed without the prior written consent of the Trustees of the University of Pennsylvania 
- 1 - 
 
 
 
CLINICAL RESEARCH PROTOCOL 
TEST ARTICLE: 
Cytalux™ (pafolacianine) injection: folate analog 
ligand conjugated with an indole cyanine green-
like dye as a solution in vials containing 1.6 mL at 
2 mg/mL
 
PROTOCOL TITLE: 
Single Dose Investigator Initiated Pilot Study to 
Investigate 
CYTALUX 
(pafolacianine) 
for 
Intraoperative 
Imaging 
of 
Patients 
with 
Endometrial Cancer Planned for Surgery 
IND NUMBER: 
Exempt 
PRINCIPAL INVESTIGATOR: 
Janos L. Tanyi, MD, PhD 
ORIGINAL PROTOCOL 
DATE: 
10 June 2025 
VERSION NUMBER: 
Version 3.0 
VERSION DATE: 
03 Sep 2025 
 

 
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TABLE OF CONTENTS 
CLINICAL RESEARCH PROTOCOL ..........................................................................1 
TABLE OF CONTENTS ..................................................................................................2 
1 
PROTOCOL SUMMARY .........................................................................................4 
1.1 
Study Synopsis ........................................................................................................4 
1.2 
Study Schematic .....................................................................................................6 
1.3 
Schedule of Activities (SoA) ..................................................................................7 
2 
INTRODUCTION ......................................................................................................7 
2.1 
Study Rationale ......................................................................................................7 
2.2 
Background ............................................................................................................8 
2.3 
Overview of Study Drug ........................................................................................8 
2.4 
Risk/Benefit Assessment ......................................................................................10 
3 
OBJECTIVES AND ENDPOINTS .........................................................................11 
4 
STUDY DESIGN ......................................................................................................12 
4.1 
Overall Design ......................................................................................................12 
4.2 
Scientific Rationale for Study Design .................................................................13 
4.3 
Justification for Dose ...........................................................................................13 
4.4 
End of Study Definition .......................................................................................13 
5 
STUDY POPULATION ...........................................................................................13 
5.1 
Inclusion Criteria .................................................................................................13 
5.2 
Exclusion Criteria ................................................................................................14 
5.3 
Lifestyle Considerations ......................................................................................14 
5.4 
Screen Failures .....................................................................................................14 
5.5 
Strategies for Recruitment and Retention .........................................................14 
6 
STUDY INTERVENTION ......................................................................................14 
6.1 
Study Intervention(s) Administration ................................................................14 
6.2 
Preparation/ Handling/ Storage/ Accountability ..............................................15 
6.3 
Measures to Minimize Bias – Randomization and Blinding ............................17 
6.4 
Study Intervention Compliance ..........................................................................17 
6.5 
Concomitant Therapy ..........................................................................................17 
6.6 
Rescue Medication ...............................................................................................18 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................18 
7.1 
Discontinuation of Study Intervention ...............................................................18 
7.2 
Participant Discontinuation / Withdrawal from the Study..............................18 
7.3 
Lost to Follow-up .................................................................................................18 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................19 
8.1 
Study Activities by Visit ......................................................................................19 
8.2 
Efficacy Assessments ...........................................................................................20 
8.3 
Adverse Events and Serious Adverse Events ....................................................20 
9 
STATISTICAL CONSIDERATIONS ....................................................................24 
9.1 
Statistical Hypotheses ..........................................................................................24 
9.2 
Statistical Analyses...............................................................................................24 

 
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10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................25 
10.1 
Regulatory, Ethical, And Study Oversight Considerations .............................25 
10.2 
Additional Considerations ..................................................................................28 
10.3 
Protocol Amendments .........................................................................................28 
11 REFERENCES .........................................................................................................29 
12 INVESTIGATOR SIGNATURE ............................................................................30 
 
 
 

 
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1 PROTOCOL SUMMARY 
1.1 
Study Synopsis 
Title:  
Single Dose Investigator Initiated Pilot Study to Investigate CYTALUX 
(pafolacianine) for Intraoperative Imaging of Patients with Endometrial 
Cancer Planned for Surgery
Study 
Description:  
This is a single center, single dose, open-label investigator-initiated pilot 
study in adult subjects with a primary diagnosis of endometrial cancer 
who are being evaluated for surgery.  
 
Subjects will receive one dose of CYTALUX™ (pafolacianine) injection 
intravenously prior to the planned diagnostic laparoscopies. This hour-
long infusion will be completed from 1 hour to up to 168 hours (7 days) 
prior to intraoperative near-infrared (NIR) imaging for the planned 
surgery. All subjects participating in the study are expected to receive 
CYTALUX™ (pafolacianine) injection and standard care laparoscopic 
evaluation of disease. Intraoperative imaging with Cytalux will be 
performed for assessment of disease detection in patients who are being 
evaluated to undergo surgery for endometrial cancer. Any tissues 
removed as part of standard of care will undergo assessment with NIR 
light imaging prior to and after resection. This will be then compared to 
gold standard histologic confirmation by pathology.
Objectives: 
Primary Objective 
To assess the ability of CYTALUX™ (pafolacianine) injection used with 
near-infrared (NIR) fluorescent imaging for the detection of malignant 
tissue in subjects undergoing surgical resection for endometrial cancer 
Secondary Objectives 
1. To assess the safety of CYTALUX in subjects undergoing surgery 
for endometrial cancer 
2. To assess folate receptor (alpha and beta expression) in resected 
specimens 
Exploratory Objectives 
1. To assess the feasibility of using genomic markers to predict utility 
of CYTALUX with NIR imaging 
2. To assess the feasibility of CYTALUX to identify sentinel lymph 
nodes
Endpoints: 
Primary Endpoint 
The primary efficacy endpoint is the sensitivity of CYTALUX with NIR 
imaging for detection of malignant lesions. Sensitivity is defined as the 
proportion of fluorescent light positive lesions that are histologically

 
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confirmed to be cancer relative to the total number of lesions confirmed to be 
cancer. 
Sensitivity = (True Positive)/(True Positive + False Negative) 
 
Secondary Endpoints 
1. Incidence rates of all adverse events (AEs), adverse device effects 
(ADEs), and SAEs, from the time of CYTALUX administration 
through Visit 3 
2. Sensitivity for cancerous lesions for: 
a. FRα positive lesions  
b. FRβ positive lesions  
Exploratory Endpoints 
1. Genomic evaluation of tumor inclusive of, but not limited to: 
a. Estrogen receptor/progesterone receptor (ER/PR) status 
b. HER2 status 
c. Mismatch repair (MMR) status 
d. POLE status 
e. p53 status 
f. CARIS whole genome sequencing  
2. The exploratory endpoint is the detection rate of CYTALUX with 
NIR imaging for identification of sentinel lymph nodes (SLNs). The 
detection rate is the proportion of the patients with SLNs detected 
by CYTALUX and NIR imaging in all enrolled patients.
Study 
Enrollment: 
This study plans to enroll 10 subjects.  
Study 
Population:  
Adult subjects (>18 years old) undergoing surgery for endometrial cancer 
Phase: 
Investigator sponsored study (ISS) 
Description of 
Sites/Facilities 
Enrolling 
Participants:  
Department of Obstetrics and Gynecology  
Jordan Center for Gynecologic Cancer at Penn Perelman Center for 
Advanced Medicine 
3400 Civic Center Boulevard 
3rd Floor West 
Philadelphia, PA 19104

 
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Description of 
Study 
Intervention: 
 CYTALUX™ (PAFOLACIANINE) INJECTION: folate analog ligand 
conjugated with an indole cyanine green-like dye as a solution in vials 
containing 1.6 mL at 2 mg/mL. Each subject will be administered a single 
intravenous dose of not less than 1 hour before and not more than 168 hours 
(7 days) before initiation of intraoperative NIR fluorescent imaging. 
The imaging systems used in this study will be assessed for meeting the 
criteria for use with CYTALUX™ (PAFOLACIANINE) INJECTION.  
Study 
Duration: 
The recruitment period is estimated at 12 months.  
Participant 
Duration: 
The maximum duration a subject is in the study is approximately 2 months.
1.2 
Study Schematic 
 
 

 
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1.3 
Schedule of Activities (SoA) 
 
 
Study Procedure 
Screening 
Visit 
 
Visit 1 
 
Visit 2 
 
Visit 3 
 
-30 days 
prior to 
surgery 
-7 days to 
day of 
surgery 
Day of 
surgery 
4 weeks ±1 
week post-
surgery 
Informed consent 
X 
 
 
 
Medical history 
X 
 
 
 
Confirmed surgical candidate  
X 
 
 
 
Pregnancy test for patients of 
childbearing potential
 
X 
 
 
Study drug administration 
 
X 
 
 
Surgery with associated procedures 
including intraoperative imaging 
and sentinel lymph node biopsy
 
 
X 
 
Histopathology assessment of 
resected tissue* 
 
 
X 
 
Collection of genomic marker data** 
 
 
X 
 
AE assessments 
 
X 
X 
X 
ADE assessments 
 
 
X 
X 
*Lesions will be resected during the surgery at Visit 2. Histopathology assessment and immunohistochemistry 
staining will be completed in accordance with local pathology procedures and timeline. 
**Genomic marker data obtained prior to surgery will be utilized, if available. If tissue is collected during surgery for 
genomic testing, the testing will be completed in accordance with institutional procedures and timeline.  
2 INTRODUCTION 
2.1 
Study Rationale 
 
Intraoperative molecular imaging, specifically with pafolacianine (CYTALUX), has proven to be a 
valuable real-time adjunctive tool in identifying cancerous lesions for adults undergoing surgery for 
ovarian and lung malignancies. Marketing authorization for pafolacianine was granted by the FDA 
(trade name CYTALUX) on November 29, 2021. 
 
Based on clinical evidence and experience from the phase 2 and phase 3 open-label trials for ovarian 
cancer and literature demonstrating the overexpression of FR, it is possible that CYTALUX could 
improve the surgeon’s ability to comprehensively stage and resect all disease in endometrial cancer, 
which is important for delivering appropriate adjuvant therapy and improving outcomes for patients. 
Endometrial cancer is increasing in incidence, especially high-risk tumors. Innovative tools are needed 
to provide treatment for this patient population.  
This study aims to explore the indication of CYTALUX™ (PAFOLACIANINE) for endometrial cancer. 
This study will evaluate the efficacy of CYTALUX™ (PAFOLACIANINE) binding to endometrial 
cancers to detect macroscopic cancers during cytoreductive surgery and assess the sensitivity as an 
intraoperative imaging adjunct.   

 
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Over 80% of advanced (stage III or IV) or recurrent endometrial carcinomas express folate receptor 
(FR), a folate binding protein, making this receptor an ideal target for marking most endometrial cancers 
(May 2025, Senol 2015). This also makes FR an ideal target for intraoperative imaging of this cancer, 
facilitating cytoreduction, and potentially improving outcomes in these patients (Kalli 2008). 
Chemotherapy does not appear to affect FR alpha (FRα) expression in endometrial cancer specimens as 
examined by immunohistochemistry (Despierre 2013), so prior treatment is unlikely to affect utility of 
FR ligands as imaging agents.  
Immunohistochemistry for FR of representative samples of resected tissue will be performed. This is 
essential to interpret the results of CYTALUX™ (PAFOLACIANINE) binding and intraoperative 
fluorescence imaging. Since cytoreductive surgeries typically have several specimens with large 
amounts of tumor, representative samples from pathology proven sites of cancer will be tested for folate 
expression and will be correlated with intraoperative fluorescence imaging.  
Information on genomic markers for patients receiving CYTALUX will be collected and correlated with 
intraoperative fluorescence imaging to help predict the utility of CYTALUX with NIR imaging.  
2.2 
Background 
Endometrial cancer is the fourth most common cancer for women in the United States (ACS 2025). 
Incidence has increased by more than 1% per year since the mid-2000s and mortality is increasing as 
well; from 2013 to 2022 the death rate rose by 1.5% per year. (ACS 2025).  
Based on data from SEER 2015-2021, the overall five-year survival rate is 81.1% and for distant disease 
it is only 19.4% (SEER 2025). The standard management of endometrial cancer is surgery. Other 
treatments such as radiation, chemotherapy, and immunotherapy may be utilized as well. Tumor-specific 
intraoperative fluorescence imaging may improve staging and debulking efforts real time during 
surgery. 
2.3 
Overview of Study Drug 
On Target has developed pafolacianine, a folate analog ligand conjugated with an indole cyanine green-
like dye as a tumor-specific imaging agent. Pafolacianine binds specifically to the high affinity folate 
receptor (FR) and could be suitable for use as an imaging agent in patients with tumors that overexpress 
FR. Following intravenous injection of pafolacianine, the agent distributes throughout the body and is 
rapidly cleared from healthy tissue, while areas with a high concentration of folate receptors, such as 
several carcinomas, retain the agent.  This fluorescence of the malignant tissue can be captured by an 
imaging system that can be used by the surgeon along with normal perioperative procedures such as 
palpation and visual observation to decide which tissues to remove during cytoreduction surgery, 
particularly after neoadjuvant chemotherapy. Clinical data demonstrate that near infrared (NIR) imaging 
devices that excite at 760 nm to 785 nm and detect emission at 790 nm to 815 nm are suitable for use 
with CYTALUX. 
Pafolacianine will bind to the FRα receptors and enter the cell through endocytosis. Upon exciting the 
area under NIR in the appropriate range, the lesions will fluoresce, helping the surgeon identify the 
osteosarcoma cancer, enabling more complete resection, identification and removal of cancerous 
synchronous lesions, and adequate margins free of the disease. Pafolacianine has been evaluated in 

 
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ovarian cancer (Phase 1, Phase 2, and Phase 3), and also in Phase 2 and Phase 3 studies for 
intraoperative imaging during surgery for cancer in the lung. In these studies, additional cancer or 
positive cancer margins were identified in 25% to 40% of the subjects.  
In studies using a human cervical carcinoma cell line (KB) that overexpresses FRα, pafolacianine 
demonstrated a high affinity for FR (KD = 10.4 nM), which compared well with the binding affinity of 
folic acid (KD = 7.4 nM). In contrast, the D-isomer of pafolacianine (OTL0039) exhibited relatively 
lower affinity for the receptor (KD = 81.8 nM). Pafolacianine competed well with [3H]-folic acid for the 
receptor, indicating that pafolacianine is highly specific for FRα. In studies conducted in nude mice 
bearing KB xenografts, fluorescence was observed primarily in the tumors 2.5 hours after intravenous 
(IV) administration of 10 nmoL pafolacianine, with weaker fluorescence signal also seen in the kidneys. 
Similar sequestration of pafolacianine into the cancer cells is expected to occur when administered to 
subjects with ovarian cancer undergoing cytoreductive surgery, leaving only FRa+ cells visible under 
the appropriate excitation wavelength. 
The safety profile of pafolacianine has been characterized in a comprehensive series of non-human 
pharmacokinetic and toxicology studies. The results of the pafolacianine Phase 1-enabling nonclinical 
safety program in rats and dogs demonstrated the safe use of pafolacianine as an intraoperative imaging 
agent. Additionally, a photoactivation study in rats showed no evidence of phototoxicity associated with 
pafolacianine. The results of the pafolacianine Phase 1-enabling nonclinical safety program in rats and 
dogs demonstrated the safe use of pafolacianine as an intraoperative imaging agent. Additionally, a 
photoactivation study in rats showed no evidence of phototoxicity associated with pafolacianine. 
On Target Laboratories has completed the following clinical studies: 
 Phase 1 ADME C14 An open-label, mass balance study to investigate the absorption, 
distribution, metabolism and excretion of [14C]-OTL0038 after a single intravenous dose to 
healthy volunteers (OTL-2019-14COTL0038-001) 
 Phase 1a Clinical Study of CYTALUX™ (pafolacianine) injection in healthy volunteers, dosed 
in 23 subjects with a dose range of 0.025 – 0.20 mg/kg (CHDR1321A). 
 Phase 1b Clinical Study of CYTALUX™ (pafolacianine) injection for the intra-operative 
imaging of folate receptor alpha positive ovarian cancer, dosed in 12 subjects with a dose range 
of 0.0125 – 0.0500 mg/kg (CHDR1321-B). 
 Phase 2 Ovarian Clinical Study of CYTALUX™ (pafolacianine) injection for the intra-operative 
imaging of folate receptor alpha positive ovarian cancer, dosed in 44 subjects with a dose of 
0.025 mg/kg (OTL-2016-CYTALUX™ -003). 
 Phase 2 Lung Clinical Study of CYTALUX™ (pafolacianine) injection for the intra-operative 
imaging of folate receptor alpha positive lung cancer, dosed in 100 subjects with a dose of 0.025 
mg/kg (OTL-2016-CYTALUX™ -005). 
 Phase 3 Ovarian Clinical Study of CYTALUX™ (pafolacianine) injection for the intra-operative 
imaging of folate receptor positive ovarian cancer, dosed in 150 subjects with a dose of 0.025 
mg/kg (OTL-2016-CYTALUX™ (pafolacianine) injection-006) 

 
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 A Phase 3, Single dose, Single-Arm, Open-Label Study to Investigate the Safety and Efficacy of 
CYTALUX™ (pafolacianine) injection for Intraoperative Imaging of Folate Receptor Positive 
Lung Nodules, dosed in 112 subjects at a dose of 0.025 mg/kg (ELUCIDATE study) (OTL-
2019-CYTALUX™ -007). 
2.4 
Risk/Benefit Assessment 
2.4.1 
Known Potential Risks 
The safety of CYTALUX was evaluated in four open label clinical studies, two studies (N = 44 and N = 
150) in patients with ovarian cancer and two studies (N = 100 and N = 112) in patients with known or 
suspected cancer in the lung. A total of 406 patients received 0.025 mg/kg of CYTALUX via intravenous 
administration.  Adverse reactions that occurred in ≥ 1% of patients were: nausea (13%), vomiting (5%), 
abdominal pain (2%), flushing (2%), other infusion-related reactions (2%), hypersensitivity (2%), 
elevation in blood pressure (1%), dyspepsia (1%), and chest discomfort (1%).   Adverse reactions occurred 
during the administration of CYTALUX in 17% of patients. During the administration of 
PAFOLACIANINE, interruption of the infusion and/or treatment with an anti-histamine may be required 
in subjects who experience symptoms suggestive of hypersensitivity, followed by an observational period 
until the symptoms resolve. Anti-nausea (e.g. Zofran) and anti-histamine (e.g. benadryl) are frequently 
dosed prior to infusion of Pafolacianine in clinical practice to limit side effects.  Symptoms to be aware 
of may include but are not limited to flushing, nausea, vomiting, abdominal pain and pruritis/urticaria. 
Other risks to subjects may include injection site adverse reactions (infusion and venous blood sampling), 
such as infection and hematoma. The use of a near-infrared fluorescence camera system during surgery 
may result in contamination of the sterile field or injury due to disengagement of the imaging device 
component coming in contact with the patient and/or surgical team. No clinically meaningful changes in 
vital signs, laboratory parameters, or electrocardiograms have been observed. Adverse events in the prior 
studies have been attributable to the underlying disease or to surgery (most commonly lymphedema, post-
procedural hematoma, or urinary incontinence). Overall, the administered doses of PAFOLACIANINE 
have been well tolerated. The time spent visualizing the surgical field under NIR is quite short, with no 
meaningful prolongation of anesthesia. There are no known hazards associated with exposure of tissue to 
near-infrared light for short periods of time. 
2.4.2 
Known Potential Benefits 
 
The potential benefits of CYTALUX for the imaging of endometrial cancer are:  
 Identification of endometrial cancer burden 
 Improved staging of the tumor 
 Identification of tissues for further evaluation 
2.4.3 
Assessment of Potential Risks and Benefits 
The anticipated benefits appear to outweigh the known and potential risks associated with exposure to 
PAFOLACIANINE. 
 

 
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3 OBJECTIVES AND ENDPOINTS 
OBJECTIVES
ENDPOINTS
Primary 
To assess the ability of CYTALUX™ 
(pafolacianine) injection used with near-
infrared (NIR) fluorescent imaging for the 
detection of malignant tissue in subjects 
undergoing surgical resection for endometrial 
cancer  
Sensitivity is defined as the proportion of fluorescent 
light positive lesions that are histologically confirmed to 
be cancer relative to the total number of lesions 
confirmed to be cancer. 
Sensitivity = (True Positive)/(True Positive + False 
Negative)
Secondary 
1. To assess the safety of CYTALUX in 
subjects undergoing surgery for 
endometrial cancer 
1. Incidence rates of all adverse events (AEs), 
adverse device effects (ADEs), and SAEs, 
from the time of CYTALUX administration 
through Visit 3
2. To assess folate receptor (alpha and 
beta expression) in resected specimens 
2. Sensitivity for cancerous lesions for: 
a. FRα positive lesions  
b. FRβ positive lesions  
Exploratory 
1. To assess the feasibility of using 
genomic markers to predict utility of 
CYTALUX with NIR imaging 
1. Genomic evaluation of tumor inclusive of, but 
not limited to: 
a. Estrogen 
receptor/progesterone 
receptor (ER/PR) status 
b. HER2 status 
c. Mismatch repair (MMR) status 
d. POLE status 
e. p53 status 
f. CARIS whole genome sequencing 
2. To assess the feasibility of 
CYTALUX to identify sentinel lymph 
nodes 
2. The exploratory endpoint is the detection rate 
of CYTALUX with NIR imaging for 
identification of sentinel lymph nodes 
(SLNs). The detection rate is the proportion 
of the patients with SLNs detected by 
CYTALUX and NIR imaging in all enrolled 
patients.
 

 
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4 STUDY DESIGN 
4.1 
Overall Design 
The study will include a screening period of up to 30 days prior to planned surgery to accommodate the 
typical timing of a pre-surgical consultation between patients and their surgeon and thus avoid the need 
for subjects to present for a screening visit immediately in advance of their planned surgery. Information 
from procedures completed as part of standard care during this period can be used for purposes of the 
trial.  
4.1.1 
Screening 
Screening will overlap with the routine/standard pre-operative screening conducted by the hospital where 
the surgery is scheduled. Consented patients will be evaluated for eligibility prior to any non-screening 
study related procedures being performed. 
4.1.2 
Administration of PAFOLACIANINE  
A single dose of PAFOLACIANINE will be administered to each subject 1 to 168 hours (7 days) prior to 
NIR imaging.  
4.1.3 
Surgical Procedure  
All subjects participating in the study are expected to receive CYTALUX™ (pafolacianine) injection and 
standard care surgical evaluation of disease. Intraoperative imaging will be completed between one and 
one hundred sixty-eight hours after CYTALUX™ (pafolacianine) infusion is completed. Any tissues 
removed as part of standard of care will undergo assessment with NIR light imaging prior to and after 
resection. This will be then compared to gold standard histologic confirmation by pathology. 
After the surgical site is visualized, location of the primary tumor and any clinically suspected additional 
tumors detected under normal light and/or palpation/endoscopic visualization will be recorded 
photographically or by video as per surgeon’s standard clinical practice. Tumors detected under normal 
light will be indicated by an “o” on the image as well as on the schematic.  
 
Once normal light assessment is completed, the surgical field will be visualized using an NIR imaging 
system under fluorescence. Any tumor and/or nodules detected using the NIR imaging system will be 
recorded on the intraoperative schematic using an “X”. Those areas that were also identified under normal 
light, the “X” will be superimposed on the “O” as “”. For nodules identified only under fluorescence, 
they will be recorded only by an “X”.  
  
Light source 
Notation 
Visible light 
O 
Fluorescent 
X 
Both 
 
 

 
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4.1.4 
Surgical Tissue Processing – Resected Lesions and Lymph Nodes 
Each lesion obtained for evaluation will be sent to local pathology for processing according to their 
standard practice. An inventory of specimens sent to local pathology labeled as above will be maintained.  
 
4.2 
Scientific Rationale for Study Design 
As stated in ICH guideline E4, “Knowledge of the relationships among dose, drug concentration drug 
concentration in blood, and clinical response (effectiveness and undesirable effects) is important for the 
safe and effective use of drugs in individual patients. This information can help identify an appropriate 
starting dose, the best way to adjust dosage to the needs of a particular patient, and a dose beyond which 
increases would be unlikely to provide added benefit or would produce unacceptable side effects.”  
4.3 
Justification for Dose 
The dose used for this study will be the dose approved by FDA as described in the prescribing 
information for CYTALUX™ (pafolacianine) injection.  
4.4 
End of Study Definition 
A participant is considered to have completed the study if they have completed all phases of the study 
including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), 
Section 1.3. 
The end of the study is defined as completion of the last visit or procedure shown in the SoA.  
 
5 STUDY POPULATION 
Adult subjects (>18 years old) who are presumed high-risk patients or have advanced disease, and/or 
recurrent disease. Pregnant patients will be excluded.  
5.1 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Provision of signed and dated informed consent form 
2. Adult subjects 18 years of age and older 
3. Primary diagnosis of endometrial cancer 
4. Scheduled to undergo surgery for endometrial cancer 
5. Ability to understand the requirements of the study and agree to abide by the study restrictions 
and to return for the required assessments 

 
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6. Willingness to stop the use of folate or folic acid supplements at least 48 hours prior to infusion 
of study drug 
5.2 
Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Pregnancy or positive pregnancy test 
2. Any medical condition that in the opinion of the investigator could potentially jeopardize the 
safety of the subject 
3. History of anaphylactic reactions to products containing indocyanine green  
4. History of allergy to any of the components of CYTALUX 
5. Presence of any psychological, familial, sociological condition or geographical challenges 
potentially hampering compliance with the study protocol or follow-up schedule 
 
5.3 
Lifestyle Considerations 
None. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants, to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any serious 
adverse event (SAE). 
5.5 
Strategies for Recruitment and Retention 
Subjects will be recruited from the clinical practice of each Investigator. Follow-up visits are set to 
correspond with normal post-operative follow-ups by the surgeon. Retention is not expected to be a 
problem. 
6 STUDY INTERVENTION 
6.1 
Study Intervention(s) Administration 
6.1.1 
Study Intervention Description 
CYTALUX will be supplied in vials containing 1.6 mL of solution of 2 mg/mL OTL38 for a total of 3.2 
mg of drug per vial. The contents of the vial are a frozen blue-green solution. 

 
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6.1.2 
Dosing and Administration 
The planned dose 0.025 mg/KG will be administered via IV over 60 minutes. Subjects will complete a 
single intravenous dose not less than 1 hour before and not more than 168 hours (7 days) before 
initiation of intraoperative fluorescent imaging. Pre-treatment with antihistamines and/or anti-nausea 
medication may be used. If the patient develops any symptoms or signs suggestive of a hypersensitivity 
reaction, including during infusion of the study drug, an antihistamine, and/or antiemetic may be 
administered based on the clinical judgement of the investigator. If such symptoms or signs suggestive 
of hypersensitivity develop during the infusion of the study drug, the infusion may be interrupted and 
then resumed based on the clinical judgement of the Investigator on the condition of the patient. 
Folic acid may reduce the detection of cancerous tissue with CYTALUX. Patients should stop taking 
folate, folic acid, or folate-containing supplements 48 hours before administration of CYTALUX. 
Note that CYTALUX should not be mixed with other medicinal products and should not be given 
simultaneously through the same IV line as another medicine. 
6.1.3 
Camera/Imaging System  
The following are specifications for the imaging systems to be used in this study. 
Spectral specifications: The light engine will provide an excitation channel that closely matches the 
optimal excitation wavelength of OTL38. As shown in Figure 1, OTL38 responds to light between the 
wavelengths of 760-776 nm with maximum excitation at 774-776 nm, and fluoresces, i.e., emits light at 
wavelengths in the near-infrared (NIR) spectrum (maximum emission 794-796 nm). 
Figure 1. Excitation and Emission Spectra of OTL38 
 
Exact spectral data for OTL38 is obtained using 1 µM of OTL38 in phosphate buffered saline with Cay 
Eclipse Fluorescence Spectrophotometer (Agilent) with auto filter setting in the Research and 
Development facility, On Target Laboratories, West Lafayette, IN. 
Excitation 
Emission

 
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Temperature: The temperature (T) of the camera head will not exceed 42°C. The limit T ≤ 42°C is 
taken from IEC60601-2-18 (Medical electrical equipment: Particular requirements for the basic safety 
and essential performance of endoscopic equipment). 
Electrical and Electromagnetic Compatibility (EMC): The light engine will conform to international 
standards for EMC emission and susceptibility, as well as other specifications in IEC 60601-1-2. 
Operating Conditions: The system shall function normally over the following range of environmental 
conditions: 
Temperature: +10° C to +30° C, at sea level 
Relative humidity: 10% to 85%, non-condensing 
Enclosure: Rough surfaces, sharp corners and edges that could result in an unacceptable risk shall be 
avoided or covered. 
Enclosure of the video processor / illuminator shall prevent fingers from reaching hazardous internal 
components. 
Sterilization: Any component requiring sterilization shall tolerate the appropriate method of 
sterilization. 
Draping: Drapes shall be provided to make the system suitable for application in the sterile field. 
Light Power – Maximum Power at Exit of Illuminator: The maximum light power at the exit of the 
illuminator shall comply with skin and tissue exposure limits as defined by IEC 60825-1 and CIE S009. 
Standard – Class 3R Laser Product: The system shall comply with the safety requirements for a Class 
3R laser product according to IEC 60825-1:2007. 
Standard – Radiation Safety: The system shall comply with the standard or broadband radiation CIE 
S009/E:2002. 
Standard – General Safety: The system shall comply with general safety standards IEC 60601-1:2005 
and IEC 60601-2-18, including all applicable amendments. 
Training and Intended Use: The system can only be used by clinicians that have been qualified as 
trained by the system provider or the sponsor, and only for the intended use in this clinical study 
protocol that has been approved by an IRB. 
6.2 
Preparation/ Handling/ Storage/ Accountability 
6.2.1 
Acquisition and Accountability 
CYTALUX will be provided by On Target Laboratories.  The vials must be stored in a secure, 
temperature-controlled freezer with limited access. Unused, partially used and/or empty vials will be 
disposed of on-site according to standard site procedures. 

 
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A Pharmacist or other trained and qualified healthcare professional will prepare the IV solutions according 
to the manufacturer’s label.  
6.2.2 
Formulation, Appearance, Packaging and Labeling 
The study medication will be packaged in vials and labelled by On Target Laboratories’ clinical supplies 
designee. 
Study medication should be stored in a freezer at temperature -20°C, and with protection from light. 
A Pharmacist or other trained and qualified healthcare professional will prepare the IV solutions 
according to the manufacturer’s label. All prepared solutions should be protected from light and 
refrigerated (between 2-8°C) until use. 
6.2.3 
Product Storage and Stability 
Study medication should be stored in a freezer at temperature, -25 to -15°C, and with protection from 
light.  If not immediately used, store the diluted CYTALUX infusion solution in a refrigerator at 2°C to 
8°C for not more than 24 hours. Once the bag is removed from refrigeration, the infusion must be 
completed within 3 hours.  
6.2.4 
Preparation 
CYTALUX will be prepared according to the manufacturer’s prescribing information.  
Note that CYTALUX should not be mixed with other medicinal products and should not be given 
simultaneously through the same IV line as another medicine. 
6.3 
Measures to Minimize Bias – Randomization and Blinding 
This trial will be an open-label study with no randomization or blinding. All subjects will receive the 
study drug.   
6.4 
Study Intervention Compliance 
The IV infusion will be performed by qualified personnel and overseen by the investigator or a medically 
qualified delegate. The date and time of the infusion will be recorded, as well as the amount infused. 
Subjects may elect to have the infusion discontinued as for example if they withdraw consent for the study, 
or experience one or more adverse events that are suspected to be attributable to the test article or its 
infusion. 
6.5 
Concomitant Therapy 
Necessary supportive measures for optimal medical care will be given throughout the study. Additional 
care may be administered as indicated at the discretion of the treating physician, and where appropriate 
after discussion with the medical monitor. Concomitant medications will include all medications that 
started, or were continuing, during or after administration of the study drug.  
The following concomitant medications are prohibited within 48 hours prior to drug administration: 
folic acid, folate supplements, and multi-vitamins containing folate. 

 
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6.6 
Rescue Medication 
Rescue medication is not applicable to this study. 
 
7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
Discontinuation from infusion of CYTALUX does not mean discontinuation from the study, and 
remaining study procedures should be completed as indicated by the study protocol.  If a clinically 
significant finding is identified (including, but not limited to, changes from baseline) after enrollment, the 
investigator or qualified designee will determine if any change in participant management is needed. Any 
new clinically relevant finding will be reported as an adverse event (AE). 
The data to be collected at the time of study intervention discontinuation will include the following: 
 The weight of the infusion bag, or a measurement of remaining volume 
 The time of discontinuation 
 The reason for discontinuation 
7.2 
Participant Discontinuation / Withdrawal from the Study 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best interest 
of the participant 
• 
Cancelation or rescheduling surgery 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
The reason for discontinuation or withdrawal from the study will be recorded. Subjects who sign the 
informed consent form and are randomized but do not receive the study intervention may be replaced.  
Subjects who sign the informed consent form, and are randomized and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, will not be replaced. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if they fail to return for scheduled safety follow-up visits 
and is unable to be contacted by the study site staff.  
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
 The site will attempt to contact the participant and reschedule the missed visit within one week of the 
target date, and counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain if the participant wishes to and/or should continue in the study. 
 Before a participant is deemed lost to follow-up, the investigator or designee will make every effort to 
regain contact with the participant (where possible, 3 telephone calls and, if necessary, a certified letter 
to the participant’s last known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record or study file.  
Should the participant continue to be unreachable, he or she will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 

 
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8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Study Activities by Visit 
Each subject who enters study screening (i.e. signs an informed consent form) will be assigned a subject 
ID number for traceability. Any subject who signs an informed consent but fails to meet the eligibility 
criteria is considered to be a Screen Failure. Screen Failure subjects will have their demographic 
information and reason for screen failure captured. 
8.1.1 
Screening Visit  
[Purpose: To determine initial eligibility and assign dose timing]  
Screening can take place up to 30 days prior to the scheduled surgery. Prior to the initiation of study-
specific screening assessments the Investigator or designee must provide the patient with a complete 
explanation of the purpose of the study and the planned evaluations (procedures and assessments). To be 
screened, the patient must sign and receive a copy of an Informed Consent Form and authorization of use 
and disclosure of protected health information (PHI) that was approved by the governing IRB. All 
consenting subjects will be screened for trial eligibility by completing the following procedures at this 
visit: 
1. Assess all Inclusion/Exclusion Criteria  
2. Obtain demographic data  
3. Record endometrial cancer diagnosis information  
4. Record relevant medical history 
 
8.1.2 
Visit 1: Infusion 
 
[Purpose: To infuse CYTALUX™ (PAFOLACIANINE) INJECTION] 
 
1. Patients with a known allergy to CYTALUX (pafolacianine) will be given pre-medication of 25 mg 
Benadryl and 4 mg Zofran as prophylaxis approximately 30 minutes prior to the start of infusion, 
unless a patient has a history of allergy to either drug. 
2. A single dose of CYTALUX will be infused IV over 60 minutes 
3. AEs will be recorded during infusion of CYTALUX. 
Should the patient experience suspected adverse events during infusion, the infusion will be 
stopped, and the Principal Investigator (PI) will be contacted for discussion and assessment. Per 
PI discretion, the patient will be treated for symptoms and infusion can be started again to assess 
for tolerance. If infusion is still not tolerated, amount infused will be recorded and imaging portion 
of study will proceed. 
4. Intraoperative imaging should begin within 1 to 168 hours (7 days) after the completion of infusion. 
 
8.1.3 
Visit 2: Surgery 
[Purpose: To collect data on the performance of intra-operative molecular imaging] 
 
1. AEs and ADEs will be recorded during and following surgery. 

 
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2. After the surgical site is visualized under normal light and/or palpation, the number and location of 
suspect lesions detected under normal light will be recorded on the schematic using an “O”.  
3. Following the assessment by normal light, subjects will undergo fluorescence imaging of the surgical 
field.  Suspect lesions detected under fluorescence imaging will be marked on the schematic using an 
“X”.  
4. All identified suspect lesions will be marked on the schematic (“O”, “X”, or “” as described in 
Section 4.1.3) and excised, at the discretion of the Investigator.  
5. Sentinel lymph node biopsy will be performed at the Investigator’s discretion per the standard of care.  
6. All excised lesions will be sent to the local laboratory for histopathology and immunohistochemistry 
staining. A unique identifier will be assigned to each excised lesion and the location of each will be 
recorded along with the unique identifier. If an organ/large section of tissue (e.g. uterus, omentum) 
with multiple lesions is excised in toto, one grossly positive lesion will be utilized for the purposes of 
calculating sensitivity and FR expression. 
7. Histopathology, folate receptor expression, and genomic testing results will be recorded once data is 
received per institutional practices and timeline. 
 
8.1.4 
Follow-Up Visit (4 weeks, +/- 1 week) 
 
[Purpose: To evaluate subjects for any new adverse experiences, and to ascertain the status of previously 
unresolved AEs] 
 
This visit may take place in person or over the phone.  
1. Inquire about new and unresolved AEs and ADEs 
 
8.2 
Efficacy Assessments 
8.2.1 
Surgical Reporting Schematics 
Surgical Schematics will be used to record the lesions for each patient (see APPENDIX 1).  
8.2.2 
Pathology Samples 
All excised lesions will be processed according to local pathology practices. The final pathology results 
will be recorded in the CRF.  
8.3 
Adverse Events and Serious Adverse Events 
8.3.1 
Definition of Adverse Events (AE) and Adverse Device Events (ADE) 
An AE is any untoward medical occurrence temporally associated with the use of an investigational 
medicinal product, whether or not considered causally related to that product. An AE can be any 
unfavorable and unintended sign (for example, an abnormal laboratory finding), symptom, or disease. 
The Investigator, or his/her designee, will document AEs.  Only AEs and ADEs considered causally 
related to the investigational product will be documented during the trial period.  

 
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An ADE is an AE associated with exposure to a medical device, such as the camera system and NIR 
illumination in this study. Where the abbreviation AE is used in this protocol, it can be understood to 
incorporate ADEs where appropriate. 
The Investigator should use his/her discretion in ordering additional tests as necessary to monitor the 
resolution of such events. Event outcome at resolution or at time of last follow up will be recorded as 
event resolved, resolved with sequelae, ongoing at discontinuation, or death. Events ongoing after the 
subject’s last visit will be followed per the investigator’s standard of care.  
The Investigator should consider AEs both as they relate to the investigational product and as they relate 
to the procedures involved in the trial. The Investigator is responsible for determining the initial 
relationship and severity of adverse events. 
8.3.2 
Definition of Serious Adverse Events (SAE) 
A serious adverse event (SAE) is defined by federal regulation as any AE occurring at any dose that 
results in any of the following outcomes: death, life-threatening AE, requires hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital 
anomaly/birth defect.  All SAEs will be documented during trial. 
Important medical events that may not result in death, be life threatening, or require hospitalization may 
be considered an SAE when, based upon appropriate medical judgment, they may jeopardize the subject 
and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in subject 
hospitalization, or the development of drug dependency or drug abuse. 
8.3.3 
Unanticipated Adverse Device Effect (UADE) 
Risk of Misinterpretation 
Errors may occur with the use of OTL38 during intraoperative fluorescence imaging to detect ovarian 
cancer and lesions in the lung, including false negatives and false positives. Non-fluorescing tissue in 
the surgical field does not rule out the presence of ovarian cancer or lesions in the lung. Fluorescence 
may be seen in normal tissues including bowel, kidneys, lymph nodes, and lungs as well as in inflamed 
tissues. 
8.3.4 
Classification of an Adverse Event (AE) 
8.3.4.1 
Severity of Event 
The severity of all AE will be assessed by the Investigator and should be classified as mild, moderate, or 
severe. Severity will be graded according to the following definitions: 
Mild: The subject experiences awareness of symptoms but these are easily tolerated or managed without 
specific treatment. Clinical or diagnostic observations only, intervention is not indicated. 

 
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Moderate: The subject experiences discomfort enough to cause interference with usual activity, and/or 
the condition requires specific treatment. Minimal, local or non-invasive intervention is indicated. 
Severe: The subject is incapacitated with inability to work or do usual activity, and/or the event requires 
significant treatment measures. Not immediately life-threatening but requires or prolongs 
hospitalization. 
Life Threatening: Urgent intervention is indicated. 
Fatal: The adverse event results in death or is death. 
8.3.4.2 
Relationship to Study Intervention 
AEs must have their relationship to study intervention assessed by the clinician who examines and 
evaluates the participant based on temporal relationship and his/her clinical judgment. The degree of 
certainty about causality will be graded using the categories below. In a clinical trial, the study product 
must always be suspect.  
 Related – There is evidence to suggest a causal relationship, and the influence of other factors is 
unlikely. The clinical event, including an abnormal laboratory test result, occurs within a reasonable 
time after administration of the study intervention, is unlikely to be attributed to concurrent disease or 
other drugs or chemicals, and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition. 
 Not Related – A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to study intervention administration makes a causal relationship improbable (e.g., the 
event did not occur within a reasonable time after administration of the study intervention) and in 
which other drugs or chemicals or underlying disease provides plausible explanations (e.g., the 
participant’s clinical condition, other concomitant treatments). Or, the AE is completely independent 
of study intervention administration, and/or evidence exists that the event is definitely related to 
another etiology. There must be an alternative, definitive etiology documented by the clinician 
8.3.4.3 
Expectedness 
The Investigator will be responsible for indicating whether an adverse event (AE) is expected or 
unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the patient population under study, the known risks of major surgery, or the risk 
information previously described for the study intervention. 
8.3.5 
Adverse Event Reporting 
Disease related events expected in this population may be reported by the investigator if they differ in 
nature or frequency from what is expected and appear to have a causal relationship to the test article. 
Adverse events must be reported in the subject’s source documents. It is the Investigator’s responsibility 
to forward to the site’s IRB all SAE/SUSAR/unanticipated ADE reports. 
8.3.6 
Serious Adverse Event Reporting 
 The Principal Investigator must be notified within 1 business day of study team’s knowledge of 
any event meeting the criteria and definition of a serious adverse event, regardless of attribution, 
occurring during the study or within 30 days of the last administration of the study related 
intervention.  

 
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 The investigator must report all events meeting the criteria and definition of a serious adverse 
event that are unexpected and possibly related (definite, probable or possible) to study 
intervention as per the local IRB reporting requirements.  
 Serious Adverse Events must be reported to the local IRB in accordance with the IRB’s policies. 
 The site must notify On Target Laboratories within 7 days of becoming aware of the event.  
8.3.7 
Reporting of Pregnancy 
Patients will be screened for pregnancy and excluded from the study if they are found to be pregnant. 

 
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9 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
 Primary Efficacy Endpoint:  
 The primary efficacy endpoint is the sensitivity of CYTALUX with NIR imaging for detection 
of malignant lesions. Sensitivity is defined as the proportion of fluorescent light positive lesions 
that are histologically confirmed to be cancer relative to the total number of lesions confirmed 
to be cancer. 
Sensitivity = (True Positive)/(True Positive + False Negative) 
 Secondary Efficacy Endpoints: 
1. Incidence rates of all adverse events (AEs), adverse device effects (ADEs), and SAEs, from the 
time of CYTALUX administration through Visit 3 
2. Sensitivity for cancerous lesions for: 
a. FRα positive lesions  
b. FRβ positive lesions  
 Exploratory Endpoints: 
1. Genomic evaluation of tumor inclusive of, but not limited to: 
a. Estrogen receptor/progesterone receptor (ER/PR) status 
b. HER2 status 
c. Mismatch repair (MMR) status 
d. POLE status 
e. p53 status 
f. CARIS whole genome sequencing  
2. The exploratory endpoint is the detection rate of CYTALUX with NIR imaging for identification 
of SLNs. The detection rate is the proportion of the patients with SLNs detected by CYTALUX 
and NIR imaging in all enrolled patients. 
9.2 
Statistical Analyses 
9.2.1 
General Approach 
Demographic and baseline patient characteristics will be summarized and described as numbers and 
percentages or means, median, standard deviations, quartiles and range, as appropriate. Pearson's Chi 
square tests will applied for categorized data, and students t-test and Mann Whitney U tests for continuous 
variables. Univariate analyses will be used to assess potential factors primary and secondary efficacy 

 
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endpoints as laid out below. Data analysis will be performed using the software package STATA. Free 
text options will be analyzed qualitatively. 
9.2.2 
Analysis of the Primary Efficacy Endpoint 
The primary analysis of the primary endpoint will include subjects exposed to CYTALUX™ 
(pafolacianine) 
injection 
and 
undergo 
fluorescent 
imaging 
(CYTALUX™ 
(pafolacianine) 
injection+Imaging) who: 
• 
Received study drug and were evaluated under NIR fluorescent light imaging during surgery 
The primary analysis of the efficacy endpoint will be a one-sample test for a proportion via an exact 
binomial test conducted at the two-tailed alpha level of 0.05. The test will compare the observed proportion 
against a threshold of 0.10. The efficacy of CYTALUX™ (pafolacianine) injection in combination with 
fluorescent imaging will be confirmed if the null hypothesis is rejected and the observed proportion is 
greater than 0.10. The two-sided 95% confidence interval (CI) will also be calculated.  
9.2.3 
Safety Analyses 
Safety will be described via subject incidence of treatment emergent adverse events (TEAEs) including 
serious TEAEs as well as adverse device effects (ADEs) considered as causally related.  
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Regulatory, Ethical, And Study Oversight Considerations 
10.1.1 
Informed Consent Process 
10.1.1.1 
Consent/Assent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting any study 
procedure. IRB-approved consent forms will contain at a minimum the following information: 
a. That the trial involves research. 
b. The purpose of the trial. 
c. The trial treatment(s) and the probability for random assignment to each treatment. 
d. The trial procedures to be followed, including all invasive procedures. 
e. The subject’s responsibilities. 
f. Those aspects of the trial that are experimental. 
g. The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an 
embryo, fetus, or nursing infant. 
h. The reasonably expected benefits. When there is no intended clinical benefit to the subject, the 
subject should be made aware of this. 
i. The alternative procedure(s) or course(s) of treatment that may be available to the subject, and 
their important potential benefits and risks. 
j. The compensation and/or treatment available to the subject in the event of trial-related injury. 
k. The anticipated prorated payment, if any, to the subject for participating in the trial. 
l. The anticipated expenses, if any, to the subject for participating in the trial. 

 
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m. That the subject’s participation in the trial is voluntary and that the subject may refuse to participate 
or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is 
otherwise entitled. 
n. That the monitor(s), the auditor(s), the IRB, and the regulatory authority(ies) will be granted direct 
access to the subject’s original medical records for verification of clinical trial procedures and/or 
data, without violating the confidentiality of the subject, to the extent permitted by the applicable 
laws and regulations and that, by signing a written informed consent form, the subject or the 
subject’s legally acceptable representative is authorizing such access. 
o. That records identifying the subject will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available. If the results of the trial 
are published, the subject’s identity will remain confidential. 
p. That the subject or the subject’s legally acceptable representative will be informed in a timely 
manner if information becomes available that may be relevant to the subject’s willingness to 
continue participation in the trial. 
q. The person(s) to contact for further information regarding the trial and the rights of trial subjects, 
and whom to contact in the event of trial-related injury. 
r. The foreseeable circumstances and/or reasons under which the subject’s participation in the trial 
may be terminated. 
s. The expected duration of the subject’s participation in the trial. 
t. The approximate number of subjects involved in the trial. 
10.1.1.2 
Consent Procedures and Documentation 
Consent forms will be IRB-approved and the participant will be asked to read and review the document. 
The investigator will explain the research study to the participant and answer any questions that may 
arise. A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants will have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. Participants will be informed that 
participation is voluntary and that they may withdraw from the study at any time, without prejudice. A 
copy of the informed consent document will be given to the participants for their records. The informed 
consent process will be conducted and documented in the source document (including the date), and the 
form signed, before the participant undergoes any study-specific procedures. The rights and welfare of 
the participants will be protected by emphasizing to them that the quality of their medical care will not 
be adversely affected if they decline to participate in this study. 
Only authorized trial staff should obtain consent and the most currently approved IRB consent form 
must be used. 
10.1.2 
Confidentiality and Privacy 
Subject confidentiality and privacy are strictly held in trust by the Sponsor Investigator, their staff, and 
OnTarget Laboratories, Inc. This confidentiality is extended to cover testing of biological samples in 
addition to the clinical information relating to subjects. Therefore, the study protocol, documentation, 
data, and all other information generated will be held in strict confidence. No information concerning 

 
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the study or the data will be released to any unauthorized third party without prior written approval of  
the Principal Investigator and OnTarget Laboratories, Inc..  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, or the 
FDA may inspect all documents and records required to be maintained by the investigator, including but 
not limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in 
this study. The clinical study site will permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, or sponsor requirements. 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, will be 
stored in the secure and password protected IU REDCap data management system. Any data or images 
transmitted to OnTarget Laboratories, Inc., manufacturer and provider of CYTALUX™ 
(PAFOLACIANINE) INJECTION, will be deidentified; individual subjects and their research data will 
be identified by a unique study identification number.  
10.1.3 
Future Use of Stored Specimens and Data 
This protocol does not include storage of any biological samples for future testing. All study data will 
remain de-identified and kept securely by the sponsor or by a qualified contracted vendor, for at least the 
period of time required by FDA. 
10.1.4 
Safety Oversight 
Safety oversight will be under the direction of a licensed physician with training, experience and 
qualifications. This study is a low-risk study utilizing an FDA-approved agent for intra-operative 
imaging. 
10.1.5 
Data Handling and Record Keeping 
10.1.5.1 
Data Collection and Management Responsibilities 
During the trial, the Investigator will maintain adequate records for the trial, including medical records, 
records detailing the progress of the trial for each subject, CRFs, signed informed consent forms, 
investigational product disposition records, correspondence with the IRB/IEC, AE/SAE reports, and 
information regarding subject discontinuation and completion of the trial. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. 

 
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10.1.6 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP requirements. 
The noncompliance may be either on the part of the participant, the investigator, or the study site staff. 
As a result of serious or repeated deviations, corrective and preventative actions are to be developed by 
the site and implemented promptly.  
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations.  
10.1.7 
Publication and Data Sharing Policy 
At a minimum, the trial and its results will be posted on ClinicalTrials.Gov.  The investigator/sponsor 
may prepare manuscripts for publication. 
10.2 Additional Considerations 
Not Applicable. 
10.3 Protocol Amendments 
Any permanent change to the protocol must be handled as a protocol amendment. The written 
amendment must be submitted to the IRB and the investigator must await approval before implementing 
the changes.   
If in the judgment of the IRB, the investigator, and/or, the amendment to the protocol substantially 
changes the study design and/or increases the potential risk to the subject and/or has an impact on the 
subject's involvement as a study participant, the currently approved written informed consent form will 
require similar modification. In such cases, informed consent will be renewed for subjects enrolled in 
the study before continued participation. 
Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
N/A 
Original Issue 
 
 
 
 

 
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11 REFERENCES 
1. May B, Conway N, Truong T, Linhart S, et al. FRα, B7-H4, & HER2 Expression in Endometrial 
Cancer: Assessing the Promise of Antibody Drug Conjugate Therapies. Presented at: SGO 2025 
Winter Meeting; January 30 - February 1, 2025; Whistler, British Columbia, Canada. 
2. Senol S, Ceyran AB, Aydin A, Zemheri E, Ozkanli S, Kösemetin D, Sehitoglu I, Akalin I. Folate 
receptor α expression and significance in endometrioid endometrium carcinoma and endometrial 
hyperplasia. Int J Clin Exp Pathol. 2015 May 1;8(5):5633-41. PMID: 26191275; PMCID: 
PMC4503146. 
3. Despierre E, Lambrechts S, Leunen K, Berteloot P, Neven P, Amant F, O'Shannessy DJ, Somers EB, 
Vergote I. Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian and 
endometrial 
cancer 
after 
chemotherapy. 
Gynecol 
Oncol. 
2013 
Jul;130(1):192-9. 
doi: 
10.1016/j.ygyno.2013.03.024. Epub 2013 Apr 2. PMID: 23558051. 
4. Folate receptor alpha is widely expressed and a potential therapeutic target in uterine and ovarian 
carcinosarcoma Saito, Ayumi et al. Gynecologic Oncology, Volume 176, 115 – 121 
5. Leamon CP, Low PS. Membrane folate-binding proteins are responsible for folate-protein conjugate 
endocytosis into cultured cells. Biochem J. 1993 May 1;291 ( Pt 3)(Pt 3):855-60. doi: 
10.1042/bj2910855. PMID: 8387781; PMCID: PMC1132447. 
6. American 
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7. SEER. Surveillance Epidemiology and End Results US National Cancer Institute; 2025 [cited 2025 
05 May]. Available from: https://seer.cancer.gov/statfacts/html/corp.html. 
 
 
 
 
 
 
 

 
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12 INVESTIGATOR SIGNATURE 
Study Title: 
The role of CYTALUX for endometrial cancer 
Original Version Date: 
 
DD-MMM-YYYY 
By my signature, I confirm that my staff and I have carefully read and understand this protocol, and agree 
to comply with the conduct and terms of the trial specified herein.  In particular, I/we have agreed to: 
1. Abide by all obligations stated in the Clinical Trial Agreement (Contract) 
2. Maintain confidentially and assure security of all confidential documents such as the protocol, product 
information documents, final trial reports, manuscript drafts, unpublished data, correspondence, etc. 
3. Obtain Institutional Review Board approval of trial, any amendments to the trial, recruitment 
advertisements, informed consent document, and periodic re-approval as required. 
4. Keep the Institutional Review Board and OnTarget, informed of serious adverse events and 
periodically report status of the trial to them as required. 
5. Obtain written informed consent from each participant or his/her legal representative. 
6. Make immediate reports of serious adverse events (SAE) to OnTarget or designee. 
7. Abide by manuscript preparation/authorship guidelines established at the outset of the trial. 
 
Investigator’s Signature:
___________________________________________
Investigator’s Name (please print): ___________________________________________
Date:
___________________________________________
 
 
 
 
 
 

 
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Page 31 of 31 
 
Appendix 1 Surgical Schematic Reporting Form 
 
Surgical Schematic Report Form             
                         
Study: The role of CYTALUX for endometrial cancer 
Patient Study ID No:  
Recorded by: 
Date: 
 
 
LESION DETECTION 
INDICATE LESION TYPE 
Normal Operating Environment Only
 O 
Fluorescence Only
X 
Fluorescence and Normal Operating Environment 
__________________________________________________                                      ______________________ 
Signature of person recording information 
 
 
 
 
        Date