Clinical trial NCT02872701
Conditions: Lung Neoplasms Lung Cancer
Sponsor: On Target Laboratories, LLC
Start date: 2017-05-04; Completion date: 2018-11-30
Enrollment: 100 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase 2, multi-center, single dose, open-label, exploratory study in suspected lung cancer patients scheduled to undergo endoscopic or thoracic surgery per CT/positron emission tomography imaging based on standard of care. This study aims to assess the efficacy of OTL38 and Near Infrared Imaging (NIR) at identifying pulmonary nodules within the operating theater, and to assess the safety and tolerability of single intravenous doses of OTL38.

Detailed description:
This is a phase 2, multi-center, single dose, open-label, exploratory study in suspected lung cancer patients scheduled to undergo endoscopic or thoracic surgery per CT/positron emission tomography (PET) imaging based on standard of care.

Two to three hours prior to surgery, patients will be infused with OTL38. After the patient is intubated and surgical site incised, the surgeon will locate and document all nodules identifiable by white light, manual palpation, and Near-Infrared Imaging (NIR). This will be documented and recorded. Surgery will be completed per surgeon's standard of care, afterwards the area will be reviewed under standard and infrared light. All samples will be sent for pathology and immunohistochemistry (IHC) evaluation.

Arms: arm 1: All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.
Interventions: intervention 1: OTL38 for Injection intervention 2: Near infrared camera imaging system intervention 3: Endoscopic or Thoracic Surgery
Intervention descriptions: intervention 1: Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL intervention 2: Near infrared camera imaging system intervention 3: Endoscopic or Thoracic Surgery

Protocol documents:
Prot_000.pdf: 








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Study Duration 
• Patients will complete a single dose of OTL38 
 initiation of 
intraoperative imaging. 
• Safety assessments: during infusion of OTL38; post-surgery; Day 7 (± 4), and Day 
28 (± 7) after surgery. 
• Estimated total length of study: 18 months 
• Patient accrual estimate: 12 months 
Eligibility 
Criteria 
Inclusion: 
1. Male and Female patients 18 years of age and older 
2. Confirmed diagnosis of adenocarcinoma lung cancer 
OR, 
3. Have a primary diagnosis, or at high clinical suspicion, of lung nodule(s) 
warranting surgery based on CT and/or PET imaging 
4. Who are scheduled to undergo endoscopic or thoracic surgery 
5. A negative serum pregnancy test at Screening followed by a negative urine 
pregnancy test on the day of surgery or day of admission for female patients of 
childbearing potential 
6. Female patients of childbearing potential or less than 2 years postmenopausal 
agree to use an acceptable form of contraception from the time of signing 
informed consent until 30 days after study completion 
7. Ability to understand the requirements of the study, provide written informed 
consent and authorization of use and disclosure of protected health information, 
and agree to abide by the study restrictions and to return for the required 
assessments 
Exclusion: 
1. Previous exposure to OTL38 
2. Known FR-negative lung nodules 
3. Any medical condition that in the opinion of the investigators could potentially 
jeopardize the safety of the patient 
4. History of anaphylactic reactions  
5. History of allergy to any of the components of OTL38, including folic acid 
6. Pregnancy, or positive pregnancy test 
7. Clinically significant abnormalities on electrocardiogram (ECG) at screening. 
8. Presence of any psychological, familial, sociological or geographical condition 
potentially hampering compliance with the study protocol and follow-up 
schedule 
9. Impaired renal function defined as eGFR< 50 mL/min/1.73m2 
10. Impaired liver function defined as values > 3x the upper limit of normal (ULN) 
for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), 
alkaline phosphatase (ALP), or total bilirubin. 
11. Received an investigational agent in another investigational drug or vaccine trial 
within 30 days prior to surgery 
12. Known sensitivity to fluorescent light 
Number of 
Subjects 
Up to 110 patients with suspected lung cancer will be enrolled in this study 




















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Table of Contents 
1 
PROTOCOL SYNOPSIS.......................................................................................................4 
2 
SCHEDULE OF PROCEDURES .......................................................................................14 
3 
BACKGROUND INFORMATION ....................................................................................19 
3.1 
Background ..................................................................................................................19 
3.2 
Rationale ......................................................................................................................19 
3.3 
Investigational Product ................................................................................................20 
3.3.1 
Prior Clinical Experience ...............................................................................20 
3.3.2 
Phase 1b Ovarian Cancer Study (CHDR1321-B) ..........................................20 
3.3.3 
Phase 2 Ovarian Cancer Study (OTL-2016-OTL38-003) ..............................21 
3.3.4 
Early Clinical Experience with Lung and Pituitary patients: .........................21 
3.4 
Risks and Benefits of OTL38 ......................................................................................22 
3.4.1 
Risks ...............................................................................................................22 
3.4.2 
Benefits ...........................................................................................................23 
4 
STUDY OBJECTIVES ........................................................................................................24 
4.1 
Primary .........................................................................................................................24 
4.2 
Secondary .....................................................................................................................24 
4.3 
Exploratory ..................................................................................................................24 
5 
STUDY DESIGN ..................................................................................................................25 
5.1 
Overall Investigation Plan............................................................................................25 
5.1.1 
Safety assessment ...........................................................................................25 
5.1.2 
Tumor to Background Ratio ...........................................................................25 
5.2 
Eligibility Criteria ........................................................................................................26 
5.2.1 
Inclusion Criteria ............................................................................................26 
5.2.2 
Exclusion Criteria ...........................................................................................26 
5.3 
Study Assessments .......................................................................................................27 
5.4 
Patient Discontinuation Criteria ...................................................................................27 
5.5 
Replacement of Dropouts ............................................................................................27 
5.6 
Study Drug Information and Dosage ...........................................................................27 
5.6.1 
Identification and Description of Test Article ................................................27 
5.6.2 
Packaging and Labeling .................................................................................28 
5.6.3 
Storage and Handling of Test Article .............................................................28 
5.6.4 
Study Drug Administration ............................................................................28 
5.6.5 
Camera/Imaging System ................................................................................29 


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5.6.5.1 
Summary of the Camera/Imaging System Requirements ..............29 
5.6.5.2 
Quality System Requirements........................................................30 
5.7 
Concomitant Medications ............................................................................................31 
5.7.1 
Allowed Medications......................................................................................31 
5.7.2 
Prohibited Medications ...................................................................................31 
5.8 
Schedule of Events .......................................................................................................31 
5.8.1 
Measurement and Evaluations ........................................................................31 
5.8.1.1 
Visit 1 (Screening, up to Day -28) .................................................31 
5.8.1.2 
Visit 2- Day of Surgery (Day 1): ...................................................32 
5.8.1.3 
Visit 3-Follow-up (Day 7 [± 4]): ...................................................36 
5.8.1.4 
Visits 4-Follow-up (Day 28 [±4]): .................................................36 
5.8.2 
Surgical Reporting Schematic ........................................................................37 
5.8.3 
Post-Surgery Questionnaire ............................................................................37 
5.8.4 
Pathology Samples .........................................................................................37 
5.8.5 
Camera/Imaging System Exposure ................................................................37 
6 
STUDY ENDPOINTS ..........................................................................................................38 
6.1 
Efficacy ........................................................................................................................38 
6.2 
Secondary Efficacy ......................................................................................................38 
6.3 
Exploratory ..................................................................................................................39 
6.4 
Safety ...........................................................................................................................39 
7 
PROCEDURES FOR REPORTING ADVERSE EVENTS .............................................40 
7.1 
Adverse Events Definitions .........................................................................................40 
7.2 
Adverse Device Effects Definitions.............................................................................40 
7.2.1 
Adverse Device Effect ....................................................................................40 
7.2.1.1 
Suspected Adverse Device Effect ..................................................41 
7.2.1.2 
Unanticipated Adverse Device Effect ............................................41 
7.3 
Reporting of Adverse Events .......................................................................................41 
7.3.1 
Adverse Events ...............................................................................................41 
7.3.2 
Laboratory Abnormalities ..............................................................................41 
7.3.3 
Serious Adverse Events ..................................................................................42 
7.3.4 
Reporting of Pregnancies ...............................................................................42 
7.3.5 
Disease Progression ........................................................................................42 
1.1.1 
Overdoses .......................................................................................................42 
7.4 
Classification of Adverse Events by Severity ..............................................................42 
7.5 
Classification of Adverse Events by Relationship to Study Drug Administration ......43 
7.6 
Adverse Events Qualifying for Expedited Reporting ..................................................43 


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8 
DATA RECORDING, CRF PROCESSING, AND STATISTICAL ANALYSIS ..........44 
8.1 
Data Recording and CRF Processing ...........................................................................44 
8.2 
Statistical Methods .......................................................................................................44 
8.2.1 
Sample Size Estimation ..................................................................................44 
8.2.2 
Analysis Sets ..................................................................................................45 
8.2.3 
Description of Subgroups to be Analyzed ......................................................45 
8.2.4 
Patient Demographics, Baseline Disease Status, and Disposition .................46 
8.2.5 
Statistical Analysis .........................................................................................46 
8.2.5.1 
Primary Efficacy Endpoints ...........................................................46 
8.2.5.2 
Secondary Efficacy Endpoint ........................................................47 
8.2.5.3 
Safety Evaluations .........................................................................47 
8.2.5.4 
Imaging System .............................................................................48 
8.2.5.5 
Prior and Concomitant Medications ..............................................48 
8.2.5.6 
Handling of Missing Data, Subject Withdrawals, and Treatment 
Failures ...........................................................................................49 
8.2.5.7 
Interim Analyses ............................................................................49 
9 
ETHICS .................................................................................................................................50 
9.1 
Patient Information and Consent .................................................................................50 
9.2 
Institutional Review Board ..........................................................................................50 
10 STUDY ADMINISTRATION .............................................................................................51 
10.1 Data ..............................................................................................................................51 
10.2 Study Record Retention ...............................................................................................51 
10.3 Patient Anonymity .......................................................................................................51 
10.4 Publications ..................................................................................................................51 
11 INVESTIGATOR’S STATEMENT ...................................................................................52 
12 REFERENCES .....................................................................................................................53 
APPENDICES ............................................................................................................................. 54 
Table of Figures 
Figure 1. 
TBR Imaging .......................................................................................................... 25 
Figure 2. 
Excitation and Emission Spectra of OTL38 ........................................................... 29 
Figure 3. 
Classification Table ................................................................................................ 46 


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List of Abbreviations 
Abbreviation 
Definition  
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AEL 
Accessible Emission Limits 
ALT (SGPT) 
Alanine aminotransferase (serum glutamic pyruvate transaminase) 
AST (SGOT) 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CSE 
Clinically Significant Event 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FDA 
United States Food and Drug Administration 
FITC 
Fluorescein isothiocyanate 
FN 
False Negative 
FP 
False Positive 
FR 
Folate Receptor 
GCP 
Good Clinical Practice 
 
 
IB 
Investigator Brochure 
ICH 
International Conference on Harmonisation  
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
SAE 
Serious adverse event 
SUSAR 
 Suspected unexpected serious adverse reaction 
TAM 
Tumor Associated Macrophages 
TEAE 
Treatment Emergent Adverse Event 
TN 
True Negative 
TP 
True Positive 
ULN 
Upper limit of the normal range 
WHO 
World Health Organization 
















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5.2 
Eligibility Criteria 
5.2.1 
Inclusion Criteria 
To be considered eligible to participate in this study, a patient must meet all the inclusion criteria 
listed below: 
1. Male and Female patients 18 years of age and older 
2. Confirmed diagnosis of adenocarcinoma of the lung,  
OR, 
3. Have a primary diagnosis/high clinical suspicion of lung nodule(s) warranting surgery 
based on CT and/or PET imaging. 
4. Scheduled to undergo endoscopic or thoracic surgery 
5. A negative serum pregnancy test at Screening followed by a negative urine pregnancy test 
on the day of surgery or day of admission for female patients of childbearing potential 
6. Female patients of childbearing potential or less than 2 years postmenopausal agree to use 
an acceptable form of contraception from the time of signing informed consent until 30 
days after study completion 
7. Ability to understand the requirements of the study, provide written informed consent and 
authorization of use and disclosure of protected health information, and agree to abide by 
the study restrictions and to return for the required assessments 
5.2.2 
Exclusion Criteria 
Patients will be excluded if they meet any of the exclusion criteria listed below: 
1. Previous exposure to OTL38 
2. Known FR-negative lung nodules.  
3. Any medical condition that in the opinion of the investigators could potentially jeopardize 
the safety of the patient 
4. History of anaphylactic reactions  
5. History of allergy to any of the components of OTL38, including folic acid 
6. Pregnancy, or positive pregnancy test 
7. Clinically significant abnormalities on electrocardiogram (ECG) at screening. 
8. Presence of any psychological, familial, sociological or geographical condition potentially 
hampering compliance with the study protocol and follow-up schedule 
9. Impaired renal function defined as eGFR< 50 mL/min/1.73m2 


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10. Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine 
aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), 
or total bilirubin. 
11. Received an investigational agent in another investigational drug or vaccine trial within 
30 days prior to surgery. 
12. Known sensitivity to fluorescent light 
5.3 
Study Assessments 
The assessments for this study are listed in Section 5.8. 
5.4 
Patient Discontinuation Criteria 
Although a single dose of study drug is infused on Day 1, a patient may be withdrawn from the 
study for any of the following reasons: 
• Request of the patient or patient’s representative 
• AEs or adverse device effects (ADEs) based on the judgment of the Investigator 
• The Investigator decides that it is in the patient’s best interest 
• The patient is noncompliant with the protocol 
• Lost to follow-up 
• Death 
If a subject is withdrawn at any time, the reason(s) will be recorded on the relevant page of the 
electronic case report form (eCRF). 
Patients discontinued due to AEs or ADEs will be monitored until resolution or stability of the 
event based on the judgment of the investigator. 
5.5 
Replacement of Dropouts 
Patients withdrawing for reasons other than AEs or any other tolerability issues with the treatment 
may be replaced. 
5.6 
Study Drug Information and Dosage  
5.6.1 
Identification and Description of Test Article 
OTL38 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. 
Study medication should be stored in a freezer 
 and with protection from 
light (see Site Study Reference Manual). 


























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7 
PROCEDURES FOR REPORTING ADVERSE EVENTS 
7.1 
Adverse Events Definitions 
The investigator will monitor the occurrence of AEs during the course of the study that will end 
with Visit 4. 
The following definitions of terms are guided by the United States Code of Federal Regulations 
(21 CFR 312.32(a)) and are included here. 
Adverse event is any untoward medical occurrence in a patient associated with the use of a drug 
in humans, whether or not considered drug related. 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, "reasonable 
possibility" means there is evidence to suggest a causal relationship between the drug and the 
adverse event. Suspected adverse reaction implies a lesser degree of certainty about causality than 
adverse reaction, which means any adverse event caused by a drug. 
Unexpected adverse event (adverse drug experience) or (suspected) adverse reaction means any 
adverse event or (suspected) adverse reaction that is not listed in the investigator brochure or is 
not listed at the specificity or severity that has been observed. 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: Death, a life- threatening 
adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be life-
threatening, or require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
An adverse event is considered “life-threatening” if, in the view of either the investigator or 
sponsor, its occurrence places the patient at immediate risk of death. It does not include an 
adverse event that, had it occurred in a more severe form, might have caused death. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) is any (suspected) adverse reaction 
(any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event) that is both serious and unexpected. 
7.2 
Adverse Device Effects Definitions 
7.2.1 
Adverse Device Effect 
An ADE is defined as any untoward and unintended response to a medical device, in this study, 
the camera/imaging system. This definition includes any event resulting from insufficiencies or 
inadequacies in the instructions for use or the deployment of the device, as well as any event that 
is the result of a user error [ISO 14155-1:2003 (E) 3.1]. 
All ADEs noted during the study will be reported in the eCRF. 


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7.2.1.1 
Suspected Adverse Device Effect 
A suspected ADE is a subset of all ADEs for which there is a reasonable possibility (i.e., evidence 
to suggest a causal relationship between the device and the ADE) that the device caused the event. 
Suspected ADE implies a lesser degree of certainty about causality than adverse device effect. 
7.2.1.2 
Unanticipated Adverse Device Effect 
An unanticipated ADE is any serious adverse effect on health or safety or any life-threatening 
problem or death caused 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 investigational plan or 
application, or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects [21 CFR 812.3 (s)]. 
7.3 
Reporting of Adverse Events 
7.3.1 
Adverse Events 
The safety of all patients enrolled in this study will be recorded from the time of study drug 
administration and throughout the course of the study that will end with Visit 4. 
All AEs will be recorded in the appropriate section of the eCRF. Patients withdrawn from the 
study because of AEs will be followed by the investigator until the outcome is determined. When 
appropriate, additional written reports and documentation will be provided. 
All AEs beginning after the exposure to study drug must be reported to the sponsor or its designee 
if the onset of the AE was before Visit 4. All AEs that are judged by the investigator to be not 
related to study drug need not be reported to the sponsor or its designee after Visit 4. All AEs that 
are judged by the Investigator to be at least possibly related to study drug administration must be 
reported to the sponsor or its designee regardless of how much time has elapsed since the last 
exposure to study drug. 
7.3.2 
Laboratory Abnormalities 
To the extent possible, all clinically significant laboratory abnormalities observed during the 
course of the study will be included under a reported AE describing a clinical syndrome 
(e.g., elevated blood urea nitrogen and creatinine in the setting of an AE of “renal failure” or 
elevated ALT/AST in the setting of an AE of “hepatitis”). In these cases (e.g., an AE of renal 
failure), the laboratory abnormality itself (e.g., elevated creatinine) does not need to be recorded 
as an AE. 
In the absence of a reported AE identifying a clinical syndrome that encompasses the observed 
clinically significant laboratory abnormality that “isolated” laboratory abnormality itself should 
be reported as an AE. 
Patients experiencing AEs or laboratory abnormalities will be assessed and appropriate 
evaluations performed until all parameters have returned to baseline levels, or are consistent with 
the patient’s then-current physical condition, in the opinion of the investigator. 


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7.3.3 
Serious Adverse Events 
Instructions for reporting Serious Adverse Events (SAE) and Suspected Unexpected Serious 
Adverse Reactions (SUSAR) are found on Page 2. A written report of all SAEs that occur after 
the administration of study drug and during the study (ending with Visit 4) must be submitted to 
the IRB/ethics committee (EC) and the Sponsor. SAEs/SUSARs must be reported to the Sponsor 
within 24 hours for a determination of expedited reporting to FDA, as described in Section 7.6. In 
all SAE reports, the investigator will advise whether or not the SAE is judged to be related to 
study drug administration. SAEs that occur after Visit 4 and are not reasonably associated with 
study drug do not require reporting per the instructions given below. All SAEs that are judged by 
the investigator to be at least possibly related to study drug administration must be reported to the 
sponsor or its designee regardless of how much time has elapsed since the last exposure to study 
drug. All AEs must be submitted to the IRB/EC in an annual report. 
7.3.4 
Reporting of Pregnancies 
If a patient becomes pregnant during the course of the study, the investigator or site personnel 
must notify the Medical monitor (see Page 3 for details) within 5 working days after the 
investigator or site personnel become aware of the pregnancy. If an SAE occurs in conjunction 
with the pregnancy, then the reporting time frame for an SAE must be met. 
7.3.5 
Disease Progression 
The progression of lung cancer (in patients diagnosed as such) per se will not constitute an AE. 
However, if the progression of the lung cancer meets the criteria for an SAE, then it should be 
reported as an SAE (see Page 2). 
1.1.1 
Overdoses 
Overdoses should be reported as a protocol violation. If an overdose results in an AE, the CRF 
AE page should be completed, and source documents included. If the overdose results in an SAE, 
then SAE reporting should be followed using the specific CRF pages with overdose information 
entered in the narrative section. All available clinical information relevant to overdose, including 
signs and symptoms, laboratory findings, and therapeutic measures or treatments administered, 
should be summarized and discussed. 
7.4 
Classification of Adverse Events by Severity 
The investigator must categorize the severity of each AE according to the following: 
• Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type. 
Symptoms do not require therapy or a medical evaluation; signs and symptoms are 
transient. 
• Moderate: Events introduce a low level of inconvenience or concern to the participant, but 
are usually improved by simple therapeutic measures; moderate experiences may cause 
some interference with functioning 


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• Severe: Events generally require systemic drug therapy or other treatment; they are 
usually incapacitating 
• Life-Threatening: Risk of imminent death requiring immediate intervention. 
7.5 
Classification of Adverse Events by Relationship to Study Drug 
Administration 
The relationship of each AE to the study drug administration will be assessed by the investigator; 
after careful consideration, according to the following guidelines: 
Definitely Related: An adverse event that has a timely relationship to the administration of the 
study drug and follows a known pattern of response for which no alternative cause is present  
Probably Related: An adverse event that has a timely relationship to the administration of the 
study drug and follows a known pattern of response, but for which a potential alternative cause 
may be present 
Possibly Related: An adverse event that has a timely relationship to the administration of the 
study drug, follows no known pattern of response, but a potential alternative cause does not exist 
Not related: An adverse event for which there is evidence that it is definitely related to a cause 
other than the study; in general, no timely relationship to the administration of the drug exists, or 
if so, the event does not follow a pattern of response and an alternative cause is present 
7.6 
Adverse Events Qualifying for Expedited Reporting  
All SUSARs, SAEs and unanticipated adverse device effects must be reported to On Target 
Laboratories or designee by telephone and in writing as soon as practical, but at least within 
24 hours of initial report. 
The investigator must report fatal and life-threatening SUSARs to the IRB within 7 calendar days 
of the initial receipt of information. On Target Laboratories or designee will report fatal and life-
threatening SUSARs to the regulatory authorities and all investigators within 7 calendar days of 
the initial report of information. 
The investigator must report non-fatal and non-life-threatening SUSARs to the IRB within 
15 calendar days of the initial receipt of information. On Target Laboratories or designee will 
report non-fatal and non-life-threatening SUSARs to the regulatory authorities and all 
investigators within 15 calendar days of the initial report of information. 
The investigator must report all unanticipated adverse device effects to the IRB within 
10 calendar days of the initial receipt of information. On Target Laboratories or designee will 
report all unanticipated adverse device effects to the regulatory authorities and all investigators 
within 10 working days of the initial report of information. 










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8.2.5.3.2 
Clinical Laboratory Evaluations 
The analysis of laboratory parameters will include descriptive statistics for the change from 
baseline to each post-baseline study visit as well as shifts from baseline to each post-baseline 
study visit for categorical lab parameters. In addition, shift tables (i.e., low-normal-high at 
baseline versus low-normal-high at last visit will be provided where appropriate. Urinalysis and 
pregnancy results will not be summarized but will be provided in a data listing. For all relevant 
laboratory data, values above or below normal limits will be flagged along with the direction of 
abnormality in line listings. 
8.2.5.3.3 
Vital Signs 
Vital signs will be summarized via descriptive statistics similar to that described above for 
clinical laboratory evaluations with regard to changes from baseline. 
8.2.5.3.4 
Physical Examination 
Physical examination results will be provided in line listings only. 
8.2.5.3.5 
Electrocardiogram 
Electrocardiogram results will be provided in line listings only. 
8.2.5.3.6 
Pathology and Immunohistochemistry 
Pathology and immunohistochemistry results will be provided in line listings. 
8.2.5.4 
Imaging System 
Times on and off for the imaging system for each subject will be provided in line listings. 
8.2.5.5 
Prior and Concomitant Medications 
The prior and concomitant medications will be coded to identify the drug class and preferred drug 
name. Concomitant medications will include all medications that started, or were continuing, 
during or after administration of the study drug. Prior medications will include all recorded 
medications and supplements a patient was taking during the screening period that were stopped 
prior to administration of the study drug. 
The number and percent of subjects using concomitant medications will be tabulated by drug 
class and preferred drug name for all subjects in the safety analysis set. If a subject has more than 
one medication within a drug class, the subject will be counted only once in that drug class. If a 
subject has more than one medication that codes to the same preferred drug name, the subject will 
be counted only once for that preferred drug name. All percentages will use the number of 
subjects in the safety analysis set as the denominator. The tabular summary will be sorted by 
descending order of overall incidence for concomitant medications only. Prior medications will be 
presented in line listings only. Concomitant medications will also be provided in line listings. 




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9 
ETHICS 
The study will be conducted in compliance with applicable ICH guidelines, the ICH E6 GCP 
guideline, and regulations, guidelines, and applicable laws of the locale and countries where the 
study is conducted. The study will be conducted with the approval of a duly constituted IRB/EC 
in accordance with the requirement of United States regulation Title 21 CFR Part 56 - 
Institutional Review Boards. The nature and risks of the study will be fully explained to each 
patient and written consent obtained in accordance with the requirements of 21 CFR 50 - 
Protection of Human Subjects. Patients will be informed of their rights, including the right to 
withdraw from the study at any time. 
9.1 
Patient Information and Consent 
A properly executed, written informed consent in compliance with national and local regulations 
and GCP guidelines will be obtained from each patient prior to entering the study or performing 
any study-related procedures that are not part of the patient’s standard care. The Investigator will 
submit a copy of the informed consent document to the IRB/EC for review and approval before 
patients are enrolled. The Investigator will provide a copy of the signed informed consent to the 
patient and the original will be maintained in the patient’s medical record. 
9.2 
Institutional Review Board 
The Investigator will provide the IRB/EC with all requisite material, including a copy of the 
protocol, IB, and the informed consent document. The study will not be initiated until the IRB/EC 
provides written approval of the protocol and the informed consent document and until approved 
documents have been obtained by the Investigator, and copies received by the Sponsor. 
Appropriate reports on the progress of this study by the Investigator will be made to the IRB/EC 
and the Sponsor in accordance with the applicable government regulations and in agreement with 
the Sponsor. 




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11 INVESTIGATOR’S STATEMENT 
I have read the protocol entitled “A Phase 2, Single dose, Open-Label, Exploratory Study to 
Investigate the Safety and Efficacy of OTL38 Injection for Intraoperative Imaging of Folate 
Receptor Positive Lung Nodules” and agree that it contains all necessary details for carrying out 
the study as described. I will conduct this protocol as outlined therein and will make a reasonable 
effort to complete the study within the time designated. I will provide copies of the protocol and 
access to all information furnished by On Target Laboratories, Inc. to study personnel under my 
supervision. I will discuss this material with them to ensure they are fully informed about the drug 
and the study. I understand that the study may be terminated or enrollment suspended at any time 
by On Target Laboratories, Inc., with or without cause, or by me if it becomes necessary to protect 
the best interests of the study patients. 
 
Signature of Investigator 
 Date (day/month/year) 
Printed Name of Investigator 
 Site Number 












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Appendix 2 Detailed Description of the 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


























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Appendix 3 Detailed Description of the 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 






















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Appendix 4 Detailed Description of the 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


























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Appendix 5 Detailed Description of the 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
























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Appendix 6
Surgical Reporting Schematics 


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Appendix 7 Investigator Questionnaire 


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SAP_001.pdf: 
On Target Laboratories, Inc. 
OTL38 Injection 
Clinical Study Report OTL-2016-OTL38-005 
Version 1.0 
 
Confidential 
 
 
16.1.9. 
Documentation of Statistical Methods 
Statistical Analysis Plan, Version 1.1, 14 April 2019