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

NCT ID: NCT07210632

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2031-01-01

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Nivo800 (5mg)

5mg nivo800

Group Type: EXPERIMENTAL

Nivolumab-IRDye800

Intervention Type: DRUG

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Nivo800 + Nivo (50mg +190)

50 mg nivo800 +190 mg nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Participants will receive a single infusion of nivolumab following an infusion of nivolumab-IRDye800 (nivo800), for a combined total dose of 240 mg. This dosing applies to all cohorts except Cohort 1, which is designated as the safety group. Each cohort, other than Cohort 1, will receive no more than 240 mg in total of nivolumab and nivo800 combined. Participants will then undergo planned Standard of Care (SOC) surgical resection 1 to 4 days after the infusion.

Nivolumab-IRDye800

Intervention Type: DRUG

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Nivo800 + Nivo (100mg + 140mg)

100 mg nivo800 +140 mg nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Participants will receive a single infusion of nivolumab following an infusion of nivolumab-IRDye800 (nivo800), for a combined total dose of 240 mg. This dosing applies to all cohorts except Cohort 1, which is designated as the safety group. Each cohort, other than Cohort 1, will receive no more than 240 mg in total of nivolumab and nivo800 combined. Participants will then undergo planned Standard of Care (SOC) surgical resection 1 to 4 days after the infusion.

Nivolumab-IRDye800

Intervention Type: DRUG

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Nivo800 + Nivo (150mg + 90mg)

150 mg nivo800 +90 mg nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Participants will receive a single infusion of nivolumab following an infusion of nivolumab-IRDye800 (nivo800), for a combined total dose of 240 mg. This dosing applies to all cohorts except Cohort 1, which is designated as the safety group. Each cohort, other than Cohort 1, will receive no more than 240 mg in total of nivolumab and nivo800 combined. Participants will then undergo planned Standard of Care (SOC) surgical resection 1 to 4 days after the infusion.

Nivolumab-IRDye800

Intervention Type: DRUG

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Nivo800 + Nivo (expansion at optimal dose cohort)

Expansion at optimal dose

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Participants will receive a single infusion of nivolumab following an infusion of nivolumab-IRDye800 (nivo800), for a combined total dose of 240 mg. This dosing applies to all cohorts except Cohort 1, which is designated as the safety group. Each cohort, other than Cohort 1, will receive no more than 240 mg in total of nivolumab and nivo800 combined. Participants will then undergo planned Standard of Care (SOC) surgical resection 1 to 4 days after the infusion.

Nivolumab-IRDye800

Intervention Type: DRUG

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Interventions

Nivolumab

Participants will receive a single infusion of nivolumab following an infusion of nivolumab-IRDye800 (nivo800), for a combined total dose of 240 mg. This dosing applies to all cohorts except Cohort 1, which is designated as the safety group. Each cohort, other than Cohort 1, will receive no more than 240 mg in total of nivolumab and nivo800 combined. Participants will then undergo planned Standard of Care (SOC) surgical resection 1 to 4 days after the infusion.

Intervention Type: DRUG

Nivolumab-IRDye800

Participants will receive an infusion of nivolumab-IRDye800 (nivo800). Nivo800 has never been assessed in patients before and therefore Cohort 1 will receive only a test dose to determine the safety (3 participants). Cohorts 2-4 will receive escalating doses of nivo800, keeping the overall dose nivolumab + nivo800 no more than 240 mg. Participants will undergo planned Standard of Care surgical resection at 1-4 days after infusion.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: collaborator

Eben Rosenthal

OTHER

Sponsor Role: lead

Responsible Party

Eben Rosenthal

Barry and Amy Baker Professor and Chair

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Patrick Kelly, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Central Contacts

Nicole Jones

Role: CONTACT

nicole.l.jones@vumc.org

615-936-2807

Makenna Brown

Role: CONTACT

makenna.l.brown@vumc.org

(615)421-4370

Facility Contacts

Nicole Jones

Role: primary

nicole.l.jones@vumc.org

615-936-2807

Makenna Brown

Role: backup

makenna.l.brown@vumc.org

615-421-4370

Other Identifiers

VICCHN25046

Identifier Type: -

Identifier Source: org_study_id