Fluorescent-labeled nivolumab (Nivo800) imaging for high-grade glioma surgery

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

This trial tests whether a near-infrared fluorescent version of the immunotherapy drug nivolumab can be given before planned surgery to visualize drug distribution in adults with suspected high-grade glioma.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vanderbilt-Ingram Cancer Center (Academic / other)
• Drugs / interventions: radiation, methotrexate, cyclophosphamide, prednisone, nivolumab, Immunotherapy
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT07210632 on ClinicalTrials.gov

What this trial studies

This early-phase window study gives a single dose of nivolumab labeled with the IRDye800 fluorescent dye before standard-of-care craniotomy to permit real-time, near-infrared visualization of drug distribution in tumor tissue. During surgery, surgeons and investigators will use NIR imaging to observe where the labeled drug localizes and collect tissue samples for correlation with fluorescence. The primary focus is on safety and feasibility of the fluorescently labeled agent and on characterizing intra-tumoral drug penetration in high-grade gliomas. Data will inform whether this imaging approach can help interpret immunotherapy delivery and guide future therapeutic strategies.

Who should consider this trial

Good fit: Adults (age ≥18) with imaging consistent with high-grade glioma who are scheduled for standard-of-care surgical craniotomy and have adequate blood counts and organ function are the intended candidates.

Not a fit: Patients who are not eligible for surgical resection, have active or significant autoimmune disease or immune deficiency, or cannot travel to the study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could help surgeons and clinicians see where nivolumab reaches tumor tissue and improve understanding of drug delivery, potentially guiding better treatment decisions.

How similar studies have performed: Antibody-IRDye800 imaging has demonstrated feasibility and useful intraoperative visualization in other tumor types, but applying a fluorescently labeled checkpoint inhibitor in high-grade glioma is novel and largely untested.

Eligibility criteria

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.

Where this trial is running

Nashville, Tennessee

• Vanderbilt University Medical Center — Nashville, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Patrick Kelly, MD — Vanderbilt University Medical Center
• Study coordinator: Nicole Jones

Conditions Brain Cancer; HGG; Glioma; High Grade Glioma; High Grade Gliomas; High Grade Glioma of the Brain With BRAF Aberration; hgg; high grade glioma