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Respiratory Tract Neoplasms

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Lung Diseases

Respiratory Tract Diseases

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Vitamins

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Folic Acid

Vitamin B Complex

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Folinic Acid

Folate

Vitamin B9

Indole

All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.

Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL

OTL38 for Injection

Near infrared camera imaging system

Endoscopic or Thoracic Surgery

Sunil Singhal, MD

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.

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.

OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules

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

Sensitivity or True Positive Rate (TPR) for OTL38 in combination with fluorescent light, defined as the proportion of fluorescent light positive tissue samples (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be FR+ and lung cancer by central pathology relative to the total number of tissue samples confirmed to be FR+ and lung cancer by central pathology.

Sensitivity = (True Positive)/(True Positive +False Negative)

False positive rate (FPR) for OTL38 in combination with fluorescent light, for the purpose of this protocol, will be calculated as 1 - the Positive Predictive Value (PPV) and is defined as the proportion of fluorescent light positive tissue samples removed (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be non-cancerous, or if cancerous, not FR+ and lung cancer, by central pathology relative to the total number of tissue samples removed with fluorescent light imaging. False Positive Rate = (False Positives) / (True Positives + False Positives)

Proportion of patients with at least 1 Clinically Significant Event (CSE as a result of utilizing OLT-38 and Near Infrared Imaging

Number of patients where at least one positive margin (fluorescent cancerous cells within 5 mm of the staple line) is identified with only OTL-38 and NIR

Number of patients where at least one synchronous lesions is identified only with OTL-38 and NIR

Number of pulmonary nodules identified with OTL-38 and Near Infrared Imaging (NIR) that could not otherwise be identified by white light and palpation.

Medelis Inc.

On Target Laboratories, LLC

All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.

OTL38 for Injection: Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL

Near infrared camera imaging system: Near infrared camera imaging system

Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Patients Receiving OTL38

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Netherlands

United States

Region of Enrollment

Tim Biro

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

* Were evaluated under both normal light and fluorescent light imaging, and
* Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Sensitivity or True Positive Rate (TPR)

False Positive Rate (FPR)

Proportion of Patients With at Least 1 Clinically Significant Event (CSE)

Positive Margin Identification

Synchronous Lesion Identification

Pulmonary Nodule Identification

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

OTL38

primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Laparotomy

This study is being done to:

* test the safety of OTL38
* see if OTL38 helps light up the cancer when viewed with the special camera system
* test the safety of the special camera system for use along with OTL38 during surgery

Phase 2 Study of OTL38 for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer

A Phase 2, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection (OTL38) for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer

Sensitivity for the detection of folate receptor-alpha positive (FRAP) ovarian cancer lesions is defined as the ratio (multiplied by 100) of the number of FRAO ovarian cancer lesions confirmed by both fluorescent light and the pathology/ and immunohistochemistry lab (TP) over the number of FRAP ovarian cancer lesions confirmed by the pathology/ and immunohistochemistry lab (TP+FN). 95% lower one-sided confidence interval was used.

PPV for the detection of FRAP ovarian cancer lesions is defined as the ratio (multiplied by 100) of the number of FRAP ovarian cancer lesions confirmed by both fluorescent light and the pathology/ and immunohistochemistry lab (TP) over the number of FRAP ovarian cancer lesions confirmed by fluorescent light (TP + FP).

95% lower one-sided confidence interval was used.

SynteractHCR

The definition of AEs and SAEs for this study was consistent with the clinicaltrials.gov definitions.

All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.

OTL38

Near infrared camera imaging system: Near infrared camera imaging system

Laparotomy: primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Patient injected with a dose of 0.025 mg/kg OTL38 and undergoes intraoperative imaging

OTL38 for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer

Tommy Lee, MSHS, Vice President, Clinical Operations

Experimental

Population includes all patients who received OTL38, underwent cytoreductive surgery for sensitivity analysis, were exposed to fluorescent light using the imaging system, and had at least one FRAP target ovarian cancer lesion. Patients enrolled to the study after adequate number of lesions have been excised and submitted for pathology, and immunohistochemistry evaluation for determining sensitivity, enrolled after protocol amendment 4, were not included in the analysis population.

Sensitivity of OTL38 in Detecting Folate Receptor-alpha Positive Ovarian Cancer During Surgery.

Population includes all patients who received OTL38, underwent cytoreductive surgery for PPV analysis, were exposed to fluorescent light using the imaging system, and had at least one FRAP target ovarian cancer lesion. Patients enrolled to the study after adequate number of lesions have been excised and submitted for pathology, and immunohistochemistry evaluation for determining PPV, enrolled after protocol amendment 4, were not included in the analysis population.

Positive Predictive Value (PPV) of OTL38 in Detecting Folate Receptor-alpha Positive Ovarian Cancer During Surgery.

OTL38 for Intra-operativeImaging of Folate Receptor-alpha Positive Ovarian Cancer

All patients in this arm will receive OTL38 for injection but will not receive intraoperative imaging.

This is a phase 3, multi-center, single dose, open-label, exploratory study in suspected lung cancer patients scheduled to undergo endoscopic or thoracic surgery per CT/PET/MRI or other 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.

ELUCIDATE: Enabling Lung Cancer Identification Using Folate Receptor Targeting

A Phase 3, Randomized,Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules

The primary efficacy endpoint is the proportion of patients who demonstrate at least one CSE as a result of utilizing OTL-38 and Near Infrared Imaging.

Proportion of FAS subjects with one or more primary NIR fluorescence positive lung nodules (cancerous or non-cancerous, excluding normal lung parenchyma) not detected under normal light and/or palpation

The proportion of FAS subjects with one or more NIR fluorescence positive cancerous synchronous lesions not detected under normal light and/or palpation

The proportion of FAS subjects with the identification of a cancerous positive margin that fluoresces within (less than or equal to) 10 mm of the surgical resection staple line

Sensitivity or True Positive Rate (TPR) for OTL38 used with fluorescent light in FAS subjects, defined as the proportion of fluorescent light positive primary nodules and synchronous lesions that are histologically confirmed to be cancer relative to the total number of primary nodules and synchronous lesions confirmed to be cancer.

False Positive Rate (FPR) for OTL38 used with fluorescent light in FAS subjects, defined as the proportion of fluorescent light positive primary nodules and synchronous lesions that are histologically confirmed not to be cancer relative to the total number of fluorescent light positive primary nodules and synchronous lesions

Clinipace Worldwide

All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.

OTL38 for Injection: Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL

Near infrared camera imaging system: Near infrared camera imaging system

Near-Infrared Imaging Group

All patients in this arm will receive OTL38 for injection but will not receive intraoperative imaging.

OTL38 for Injection: Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL

No Imaging Group

Total

Tommy Lee

The full analysis set will include subjects exposed to OTL38 and randomized to undergo NIR fluorescent imaging (OTL38+Imaging) who were evaluated under both normal light and NIR fluorescent light imaging

Full Analysis Set (FAS)

Full Analysis Set (FAS): The FAS for the primary analysis of the primary efficacy endpoint will include subjects exposed to OTL38 and randomized to undergo fluorescent imaging (OTL38+Imaging) who:

• Were evaluated under both normal light/palpation and NIR fluorescent light imaging

Clinically Significant Events (CSE)

Fully Analysis Set (FAS)

Localization of Primary Nodule

Identification of Cancerous Synchronous Lesions

Positive Resection Margins

Total number of Subjects with Evaluated Tissues

Sensitivity for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects

False Positive Rate for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects

Patient injected with OTL38, but does not undergo fluorescent imaging

Patient injected with OTL38 and undergoes near infrared imaging

0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes

Infrared imaging used to excite OTL38 for fluorescence

near infrared camera imaging system

laparotomy

Janos Tanyi, MD

This is a phase 3, randomized, multi-center, single dose, open label, pivotal study in patients diagnosed with, or with high clinical suspicion of, ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery.

The Phase 3 study is to confirm the efficacy of OTL38 in combination with fluorescent light to detect additional Folate Receptor-positive (FR+) ovarian cancer lesions not detected by palpation and visualization under normal light in patients with FR+ ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

A Phase 3, Randomized, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection (OTL38) for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set)

False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set)

The "Other Adverse Events" table captures all drug-related treatment-emergent adverse events reported at or above the frequency threshold for reporting.

The Safety Analysis Set includes all subjects who received any amount of study drug.

Safety Analysis Set

Patient injected with OTL38 and undergoes near infrared imaging.

Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes

Other Names:

OTL38 for Injection Device: near infrared camera imaging system Infrared imaging used to excite OTL38 for fluorescence

Other Names:

Near IR imaging Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Experimental: OTL38 Injection and Near Infrared Imaging

Patient injected with OTL38, but does not undergo fluorescent imaging.

Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes

Other Names:

OTL38 for Injection

Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Sham Comparator: OTL38 Injection and No Fluorescent Imaging

Patients exposed to OTL38 and who were randomly assigned to undergo NIR fluorescent imaging (OTL38+imaging) and who:

* Were evaluated under both normal light and NIR fluorescent light imaging
* Had central pathology and histology confirmation for at least one FR+ ovarian cancer lesion detected under normal light or NIR fluorescent light imaging

Full Analysis Set

Efficacy Patient Level

Patient False Positive Rate

Patient injected with OTL38, but does not undergo fluorescent imaging.

Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes

Other Names:

OTL38 for Injection Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules	NCT02872701	Lung Neoplasms Lung Cancer	OTL38 for Injec... Near infrared c... Endoscopic or T...	18 Years - 85 Years	On Target Laboratories, LLC
Phase 2 Study of OTL38 for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer	NCT02317705	Ovarian Cancer	OTL38 Near infrared c... Laparotomy	18 Years -	On Target Laboratories, LLC
ELUCIDATE: Enabling Lung Cancer Identification Using Folate Receptor Targeting	NCT04241315	Lung Neoplasms Lung Cancer	OTL38 for Injec... Near infrared c...	18 Years -	On Target Laboratories, LLC
OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules	NCT02872701	Lung Neoplasms Lung Cancer	OTL38 for Injec... Near infrared c... Endoscopic or T...	18 Years - 85 Years	On Target Laboratories, LLC
OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules	NCT02872701	Lung Neoplasms Lung Cancer	OTL38 for Injec... Near infrared c... Endoscopic or T...	18 Years - 85 Years	On Target Laboratories, LLC
OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer	NCT03180307	Ovarian Cancer	OTL38 near infrared c... laparotomy	18 Years - 85 Years	On Target Laboratories, LLC

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