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

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.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasms; Lung Cancer
• Intervention / Treatment: Device: Near infrared camera imaging system; Drug: OTL38 for Injection; Procedure: Endoscopic or Thoracic Surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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 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 Criteria:

1. Previous exposure to OTL38
2. Known Folate Receptor-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 or severe allergies
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 epidermal growth factor receptor (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients Receiving OTL38; All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.	Device: Near infrared camera imaging system; Near infrared camera imaging system; Drug: 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; Other Names: OTL38; Procedure: Endoscopic or Thoracic Surgery; Endoscopic or Thoracic Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity or True Positive Rate (TPR)	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)	1 day
False Positive Rate (FPR)	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)	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Nodule Identification	Number of pulmonary nodules identified with OTL-38 and Near Infrared Imaging (NIR) that could not otherwise be identified by white light and palpation.	1 day
Synchronous Lesion Identification	Number of patients where at least one synchronous lesions is identified only with OTL-38 and NIR	1 day
Proportion of Patients With at Least 1 Clinically Significant Event (CSE)	Proportion of patients with at least 1 Clinically Significant Event (CSE as a result of utilizing OLT-38 and Near Infrared Imaging	1 day
Positive Margin Identification	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	1 day

Other Outcome Measures

Outcome Measure	Time Frame
Detection rates of adenocarcinoma between OTL38 fluorescence at time of surgery vs. frozen section assessment as determined by final pathology report.	1 day
Comparison of fluorescing lesions vs. proportion of lesions expressing Folate-Receptor alpha (FRα+) and Folate Receptor beta (FRβ+) as determined by immunohistochemical analysis	1 day
Incidence rates of all adverse events (AEs), treatment-emergent AEs (TEAEs), adverse device events (ADEs), and serious adverse events (SAEs.)	Through study completion, about 4 weeks.
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to OTL38.	Through study completion, about 4 weeks.

Collaborators and Investigators

• Sponsor: On Target Laboratories, LLC
• Collaborators: Medelis Inc.
• Investigators: Principal Investigator: Sunil Singhal, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2017
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 19, 2016

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: OTL-2016-OTL38-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes