Window Trial of Fluorescently Labeled Nivolumab-IRDye800 (Nivo800) in High Grade Glioma (HGG)

Not Applicable

Not yet recruiting

• Conditions: Brain Cancer; HGG; Glioma; High Grade Glioma; High Grade Gliomas; High Grade Glioma (III or IV); High Grade Glioma (HGG) of the Brain With BRAF Aberration
• Interventions: Drug: Nivolumab-IRDye800; Drug: Nivolumab

• Registration Number: NCT07210632
• Lead Sponsor: Eben Rosenthal

Brief Summary

High-grade gliomas (HGGs) are among the most aggressive and treatment-resistant brain tumors. Immunotherapy with checkpoint inhibitors like nivolumab has shown promise, but its efficacy remains variable and poorly understood in this patient population. This clinical trial investigates a novel imaging-enabled formulation of nivolumab-IRDye800 (nivo800) which incorporates a near-infrared (NIR) fluorescent dye to enable real-time visualization of drug distribution within tumor tissue.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-09-29
• Study First Submitted QC: 2025-09-29
• Status Verified: 2025-10
• Study First Posted: 2025-10-07
• Last Update Submitted: 2025-10-13
• Last Update Posted: 2025-10-15
• Study Start: 2026-01-01
• Primary Completion: 2030-01-01
• Study Completion: 2031-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. Written informed consent
2. Age ≥ 18 years
3. Patient must have imaging of highly suspicious high grade glioma (HGG)
4. Patients for whom surgical craniotomy is planned as standard of care (SOC)
5. Adequate hematologic and end-organ function appropriate for surgical resection and anesthesia (within 30 days of infusion) WBC ≥ 2,000 (mcl) AST 9-80 (IU/L) ALT 7-110 (IU/L) BUN 6-50 (mg/dL) Creatinine 0.5-3.0 (mg/dL) Negative hepatitis B surface antigen (HBsAg) test at screening

Exclusion Criteria

1. Patients not eligible for SOC surgical resection

2. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:

   Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.

   Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.

   Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided if all the following conditions are met:

   Rash must cover < 10% of body surface area Disease is well controlled at baseline and requires only low-potency topical corticosteroids No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency oral corticosteroids within the previous 12 months

3. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

   History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

4. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.

5. Severe unresolved infection within 4 weeks prior to initiation of study treatment.

6. Prior allogeneic stem cell or solid organ transplantation

7. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins

8. Chronic treatment with systemic immunosuppressive medication in excess of physiologic maintenance doses of corticosteroids (>10 mg/day of prednisone or equivalent) (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents), with the following exceptions:

   Patients who received acute, systemic immunosuppressant medication or a dose of systemic immunosuppressant medication are eligible for the study.

   Physiologic corticosteroid replacement therapy at doses ≤ 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.

   Patients with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.

   Patients using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.

   Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.

9. Pregnant or breastfeeding, or intention of becoming pregnant during study treatment or within 2 months after the final dose of study treatment.

10. Participants presenting with a baseline QTcF interval > than 480 milliseconds.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nivo800 (5mg)	Nivolumab-IRDye800	5mg nivo800
Nivo800 + Nivo (100mg + 140mg)	Nivolumab-IRDye800	100 mg nivo800 +140 mg nivolumab
Nivo800 + Nivo (150mg + 90mg)	Nivolumab	150 mg nivo800 +90 mg nivolumab
Nivo800 + Nivo (150mg + 90mg)	Nivolumab-IRDye800	150 mg nivo800 +90 mg nivolumab
Nivo800 + Nivo (50mg +190)	Nivolumab	50 mg nivo800 +190 mg nivolumab
Nivo800 + Nivo (100mg + 140mg)	Nivolumab	100 mg nivo800 +140 mg nivolumab
Nivo800 + Nivo (50mg +190)	Nivolumab-IRDye800	50 mg nivo800 +190 mg nivolumab
Nivo800 + Nivo (expansion at optimal dose cohort)	Nivolumab	Expansion at optimal dose
Nivo800 + Nivo (expansion at optimal dose cohort)	Nivolumab-IRDye800	Expansion at optimal dose

Primary Outcome Measures

Name	Time	Method
Determine the safety of fluorescently labeled nivolumab-IRDye800 (nivo800) as a molecular imaging agent via assessing adverse events.	From infusion to 15 days post-infusion.	As defined by the number of Grade ≥ 2 Adverse Events (AEs) determined that are clinically significant and considered definitely or probably related to nivo800. Safety data will be summarized by grade, severity, and type.

Secondary Outcome Measures

Name	Time	Method
Determine the optimal dose of nivolumab-IRDye800 (nivo800) for near-infrared (NIR) fluorescence imaging in the tumor, via microscopic imaging.	From Day of Surgery Resection to 3 months	As defined by the lowest dose of nivo800 in a total dose of 240 mg (nivolumab + nivo800 = 240 mg) that allows for successful detection of a fluorescence signal at single cell resolution on a 4mm microscopic human tissue slide imaged under a customized Leica fluorescence microscope (20x, 2x2 binning, 3 second exposure time).

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States