FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery

An Open-label, Non-randomized, Single Dose, Phase II Trial of FG001 (an Optical Imaging Agent) for Localization of Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery

In neurosurgery both the diffusely infiltrated gliomas of the brain as well as the border towards healthy tissue in the meninges is a challenge. For the high-grade contrast enhanced gliomas fluorescent drugs like Gliolan have been used in several years and proved its clinical value. For non-contrast enhanced gliomas, like low-grade glioma, no such drug exist. The transition zone towards healthy non-tumor cell infiltrated brain in such low-grade gliomas is extremely difficult but for these patients their prognosis depends on the amount of non-healthy tissue left behind. Also, in benign tumors as meningioma the complete resection including infiltrated meninges is of importance for the cure of the disease. None of the existing fluorescent drug is useful or approved for these tumors.. Hence a medicinal product that will fulfil the criteria for a safe and reliable fluorescent drug to guide the surgery to the boundaries of the infiltration with tumor cells is highly warranted.

The drug FG001 (ICG-Glu-Glu-AE105), a uPAR-targeting fluorescent drug, has been tested in patients with high-grade glioma as part of a First-in-human clinical trial and demonstrated an excellent safety profile and efficacy results. Animal studies have indicated uptake of FG001 in low-grade glioma while uptake has been shown in one clinical case of meningioma providing the basis for this trial.

Consequently, the investigators intend to test the ability of FG001 to reliably fluoresce in patients with presumed low-grade glioma or meningioma.

Inclusion Criteria:

Subjects will be entered into this trial only if they meet all the following criteria:

1. Subjects diagnosed with primary brain tumor on MRI suggestive of, meningioma or presumed low-grade glioma (pLGG)*
2. Scheduled for neurosurgery with the objective to remove cancer tissue
3. Subjects aged 18 years or older
4. Capable of understanding and giving written informed consent
5. Women of childbearing potential must agree to use an adequate method of contraception during the trial and for 30 days after the end-of-trial visit. Adequate methods of contraception include intrauterine device or hormonal contraception (oral contraceptive pill, depot injections or implant, transdermal depot patch or vaginal ring). To be considered sterilised or infertile, females must have undergone surgical sterilisation (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhoea; may be confirmed with follicle-stimulating hormone [FSH] test if there is doubt)
6. Male subjects must commit to use barrier contraception (e.g., condom) during the trial and for 30 days after the end-of-trial visit.
7. Subject must not previously have received the trial drug (FG001)
8. Subjects must have normal organ and bone marrow function and be appropriate surgical candidates per site standard of care (SOC) *Presumed low-grade gliomas in this protocol are defined as diffusely infiltrated non-contrast enhancing tumors on MRI. Patients with known LGG scheduled for re-surgery or primary surgery after a diagnostic biopsy may also be included.

Exclusion Criteria:

1. Any known allergy or hypersensitivity to indocyanine green (ICG)

2. Female subjects who are pregnant or breast-feeding (pregnancy test positive prior to inclusion (or if breast-feeding willing to pause breast feeding during trial and for 30 days

3. Overall performance status or co-morbidity deeming the subject unfitted for participation in the trial as judged by the Investigator

4. Pre-existing hepatic and/or renal insufficiency

   • INR above 1.7
   • Estimated GFR (eGFR) below 45 ml/min/1.73m2

5. Unwilling or unable to follow the protocol requirements