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FG001

A new clinical trial is investigating FG001, a promising optical imaging agent designed to help neurosurgeons better visualize brain tumors during surgery. This Phase II trial specifically focuses on patients with meningiomas or presumed low-grade gliomas who are scheduled for neurosurgery. FG001 addresses a critical challenge in neurosurgery: accurately identifying the boundaries between tumor tissue and healthy brain tissue, which is especially difficult in low-grade gliomas and meningiomas. Unlike high-grade gliomas where fluorescent drugs like Gliolan have proven valuable, there has been no equivalent solution for these other tumor types until now. Based on promising results from previous studies, this trial aims to evaluate whether FG001 can reliably highlight tumor tissues, potentially improving surgical outcomes for patients.

Table of Contents

What is FG001?

FG001 (also known as ICG-Glu-Glu-AE105) is an investigational optical imaging agent designed to help neurosurgeons better visualize brain tumors during surgery. It is currently being studied for use in patients with meningiomas (tumors that develop from the membranes covering the brain) or low-grade gliomas (slow-growing tumors that arise from the supportive tissue of the brain).[1]

FG001 is a fluorescent drug, which means it makes tumor tissue glow when viewed under special light during surgery. This helps surgeons distinguish between tumor tissue and healthy brain tissue, which can be extremely difficult to differentiate with the naked eye.[1]

How FG001 Works

FG001 is a uPAR-targeting fluorescent drug. uPAR stands for urokinase plasminogen activator receptor, which is a protein found in higher amounts in many types of cancer cells compared to normal cells. FG001 attaches to these receptors on tumor cells, causing them to fluoresce (glow) when viewed under specialized surgical microscopes during the operation.[1]

The drug has already been tested in patients with high-grade glioma (a more aggressive form of brain tumor) in a First-in-human clinical trial where it demonstrated an excellent safety profile and promising efficacy results. Animal studies have also indicated that FG001 is taken up by low-grade gliomas, and clinical evidence has shown uptake in at least one case of meningioma.[1]

Target Conditions: Low-Grade Gliomas and Meningiomas

FG001 is being developed specifically for two types of brain tumors that currently lack effective fluorescent imaging options during surgery:[1]

  • Low-Grade Gliomas: These are slow-growing tumors that develop from the glial cells that support and nourish the brain. Unlike high-grade gliomas, low-grade gliomas typically don’t enhance on contrast MRI scans and don’t have clear borders. This makes them particularly challenging to remove completely during surgery. For patients with low-grade gliomas, their prognosis depends significantly on how much tumor tissue is left behind after surgery.
  • Meningiomas: These tumors develop from the meninges, the membranes that cover the brain and spinal cord. Although often benign (non-cancerous), complete removal of meningiomas, including any infiltrated meninges, is important for curing the disease and preventing recurrence.

Currently, there are no approved fluorescent drugs for visualizing these types of tumors during surgery. While a drug called Gliolan has been used for several years for high-grade gliomas, it is not useful or approved for low-grade gliomas or meningiomas.[1]

Clinical Trial Details

FG001 is currently being evaluated in a Phase II clinical trial titled “FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery.” This is an open-label, non-randomized trial where patients receive a single dose of FG001 before undergoing neurosurgery.[1]

The study design includes:[1]

  • A total of 40 patients planned for enrollment
  • Two study arms: one for patients with presumed low-grade gliomas (pLGG) and one for patients with meningiomas
  • Initial enrollment of 20 patients (10 with pLGG and 10 with meningioma)
  • An interim analysis after the first 20 patients, which may lead to modifications in dosing time or amount
  • Enrollment of the remaining 20 patients (10 with pLGG and 10 with meningioma)

Expected Benefits of FG001

The main goal of using FG001 is to help neurosurgeons better visualize tumor boundaries during surgery. This is particularly important for:[1]

  • Identifying the difficult-to-see transition zone between healthy brain tissue and tumor-infiltrated tissue in low-grade gliomas
  • Ensuring complete resection (removal) of meningiomas, including any infiltrated meninges
  • Potentially improving surgical outcomes by maximizing tumor removal while minimizing damage to healthy brain tissue

For patients with low-grade gliomas, more complete tumor removal could potentially improve prognosis, as the amount of residual tumor tissue after surgery is known to affect outcomes. For meningioma patients, complete removal is important for cure and to prevent recurrence.[1]

How FG001 is Administered

In the clinical trial, patients receive a single intravenous (IV) injection of 36 mg of FG001. This is administered the day before the scheduled surgery. During the operation, the surgeon uses specialized equipment to visualize the fluorescence from the drug that has accumulated in the tumor tissue.[1]

The timing of administration (one day before surgery) is specifically designed to allow the drug to accumulate in tumor tissue while clearing from normal tissues, creating optimal contrast during the surgical procedure.[1]

Safety and Efficacy Measurements

The clinical trial is measuring several aspects of FG001’s performance:[1]

  1. Sensitivity: The primary objective is to evaluate the sensitivity of FG001 for detecting tumor tissue. Sensitivity is defined as the proportion of histologically verified tumors that fluoresce when exposed to FG001. In simpler terms, this measures how well the drug can detect tumor tissue that is actually present.
  2. Specificity: This measures the drug’s ability to correctly identify healthy tissue (i.e., the probability that tissue will not fluoresce when it is not cancerous).
  3. Safety: The safety of FG001 is being monitored through:
    • Physical examinations
    • Laboratory samples
    • Tracking the incidence and severity of adverse events (side effects), which are evaluated according to the National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) version 5.0

Previous studies with FG001 in patients with high-grade gliomas have already demonstrated an excellent safety profile, which provides reassurance for patients participating in this new trial for low-grade gliomas and meningiomas.[1]

Study Aspect Details
Study Type Open-label, non-randomized, single dose, Phase II trial
Investigational Drug FG001 (ICG-Glu-Glu-AE105), a uPAR-targeting fluorescent agent
Target Conditions Meningiomas and presumed low-grade gliomas
Number of Participants 40 patients (20 with presumed low-grade gliomas, 20 with meningiomas)
Dosage Single intravenous injection of 36 mg FG001 administered the day before surgery
Primary Objective Evaluate sensitivity of FG001 for detection of tumor tissue in meningiomas and presumed low-grade gliomas
Secondary Objectives Assess efficacy (sensitivity and specificity) and safety of FG001 as a tumor imaging agent
Safety Monitoring Physical examinations, laboratory samples, and monitoring of adverse events using NCI CTCAE v5.0
Study Design Initial enrollment of 20 patients followed by interim analysis before enrolling remaining 20 patients
Previous Findings FG001 showed excellent safety profile and efficacy in high-grade glioma first-in-human trial; animal studies indicated uptake in low-grade glioma; clinical case showed uptake in meningioma

FAQ

  • What is FG001 and how does it work? FG001 (ICG-Glu-Glu-AE105) is a uPAR-targeting fluorescent drug designed to make tumor tissue visible during surgery. When injected into the patient's bloodstream before surgery, it targets specific receptors (uPAR) that are present in tumor cells. During surgery, when viewed under special light, the areas where FG001 has accumulated will fluoresce or glow, helping surgeons distinguish between tumor tissue and normal brain tissue.
  • Why is FG001 being tested for meningiomas and low-grade gliomas specifically? These types of brain tumors present unique surgical challenges. Low-grade gliomas tend to infiltrate diffusely into surrounding brain tissue, making their boundaries difficult to detect. Similarly, in meningiomas, complete removal including infiltrated meninges (the protective layers covering the brain) is crucial for disease cure. Existing fluorescent drugs aren't useful or approved for these tumors. FG001 has shown promising results in animal studies for low-grade gliomas and in a clinical case of meningioma, suggesting it might help surgeons better visualize these challenging tumors.
  • How is FG001 administered in this clinical trial? Participants in this trial receive a single intravenous injection of 36 mg of FG001 the day before their scheduled neurosurgery. This timing allows the drug to circulate throughout the body and accumulate in tumor tissues, making them visible during surgery the following day.
  • What is the primary goal of this clinical trial? The primary objective is to evaluate the sensitivity of FG001 for detecting tumor tissue in meningiomas and presumed low-grade gliomas. Sensitivity refers to how accurately the drug can identify tumor tissue that is later confirmed by histological verification (examination of the tissue under a microscope). The trial will determine what proportion of patients have tumors that successfully fluoresce when FG001 is used.
  • How many patients will participate in this trial, and how is it structured? The trial plans to enroll a total of 40 patients divided into two arms: 20 patients with presumed low-grade gliomas and 20 patients with meningiomas. The study will begin with 10 patients in each arm, followed by an interim analysis. Based on these initial results, adjustments may be made to the dose or administration timing before enrolling the remaining 20 patients. This structure allows the researchers to optimize the protocol during the trial if needed.

Ongoing Clinical Trials on FG001

  • Study of FG001 for Detecting Meningioma or Low-Grade Glioma in Patients Undergoing Neurosurgery

    Not yet recruiting

    1 1
    Investigated drugs:
    Denmark

Glossary

  • Meningioma: A type of tumor that develops in the meninges, which are the layers of tissue that cover the brain and spinal cord. Most meningiomas are benign (non-cancerous), but complete surgical removal is important to prevent recurrence.
  • Low-grade Glioma: A slow-growing type of brain tumor that originates from glial cells, which support and protect neurons in the brain. These tumors tend to infiltrate diffusely into surrounding brain tissue, making complete surgical removal challenging.
  • Neurosurgery: Surgery performed on the brain, spinal cord, or peripheral nerves. In the context of brain tumors, the goal is typically to remove as much tumor tissue as possible while preserving normal brain function.
  • Fluorescent drug: A medication that causes specific tissues to glow when exposed to certain types of light. In neurosurgery, fluorescent drugs help surgeons visually distinguish tumor tissue from normal brain tissue during operations.
  • Gliolan: A fluorescent drug currently used for high-grade contrast-enhanced gliomas. It helps make tumor tissue visible during surgery but is not effective for low-grade gliomas or meningiomas.
  • uPAR: Urokinase Plasminogen Activator Receptor, a cellular receptor that is often overexpressed in tumor tissues. FG001 targets these receptors to selectively accumulate in tumor cells.
  • Optical Imaging Agent: A substance that makes specific tissues visible through imaging techniques. FG001 is an optical imaging agent that helps visualize tumor tissues during surgery.
  • Sensitivity: In medical testing, sensitivity refers to the ability of a test to correctly identify those with a disease. For this trial, it measures how accurately FG001 identifies tumor tissue that is later confirmed by microscopic examination.
  • Specificity: The ability of a test to correctly identify those without a disease. In this context, it measures how accurately FG001 avoids highlighting non-tumor tissue.
  • Histological verification: The process of examining tissue samples under a microscope to confirm the presence or absence of tumor cells. Used to validate whether tissue that fluoresced during surgery actually contained tumor cells.
  • First-in-human clinical trial: The initial study where a new drug or treatment is tested in humans after laboratory and animal testing. FG001 was previously tested in such a trial for high-grade gliomas.
  • Transition zone: The border area between tumor tissue and healthy brain tissue. This zone is especially difficult to identify in low-grade gliomas, making complete tumor removal challenging.
  • Interim analysis: A planned evaluation of data collected during a clinical trial before the study is complete. In this trial, an interim analysis will occur after enrolling the first 20 patients to determine if any protocol adjustments are needed.
  • Adverse events (AEs): Any unfavorable and unintended sign, symptom, or disease that occurs during a clinical trial, whether or not it is related to the treatment being studied. The safety of FG001 will be evaluated by monitoring these events.

References

  1. https://clinicaltrials.gov/study/NCT06684795