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

Eben Rosenthal

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Glioma; HGG; High Grade Glioma (HGG) of the Brain With BRAF Aberration; High Grade Glioma (III or IV); High Grade Glioma; Brain Cancer; High Grade Gliomas

Treatments: Drug: Nivolumab; Drug: Nivolumab-IRDye800

Study type: Interventional

Funder types: Other

Identifiers

NCT07210632

VICCHN25046

Details and patient eligibility

About

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.

Enrollment: 38 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 5 patient groups

Nivo800 (5mg)

Experimental group

Description:

5mg nivo800

Treatment:

Drug: Nivolumab-IRDye800

Nivo800 + Nivo (50mg +190)

Experimental group

Description:

50 mg nivo800 +190 mg nivolumab

Treatment:

Drug: Nivolumab-IRDye800

Drug: Nivolumab

Nivo800 + Nivo (100mg + 140mg)

Experimental group

Description:

100 mg nivo800 +140 mg nivolumab

Treatment:

Drug: Nivolumab-IRDye800

Drug: Nivolumab

Nivo800 + Nivo (150mg + 90mg)

Experimental group

Description:

150 mg nivo800 +90 mg nivolumab

Treatment:

Drug: Nivolumab-IRDye800

Drug: Nivolumab

Nivo800 + Nivo (expansion at optimal dose cohort)

Experimental group

Description:

Expansion at optimal dose

Treatment:

Drug: Nivolumab-IRDye800

Drug: Nivolumab