The goal of this Phase 1 clinical trial is to evaluate the safety and feasibility of nivolumab-IRDye800CW (nivo800) as a molecular imaging agent in adults with biopsy-confirmed or presumed head and neck squamous cell carcinoma (HNSCC) who are scheduled to undergo standard-of-care surgical resection.

The main questions it aims to answer are:

• Is nivolumab-IRDye800CW (nivo800) safe when administered before surgery, as measured by the occurrence of clinically significant Grade ≥2 adverse events that are possibly, probably, or definitely related to the study drug?
• What is the extent of pathological response at each dose level, including residual viable tumor, fibrosis, necrosis, and tumor-infiltrating lymphocyte characteristics?

Participants will:

• Receive two intravenous infusions during the preoperative period, approximately 2-3 weeks before surgery and again 1-2 days before surgery.
• Undergo standard-of-care surgical resection with collection of tumor and lymph node specimens for pathological and imaging studies.

Inclusion Criteria:

• Written informed consent
• Age ≥ 18 years
• Participants must have biopsy proven HNSCC or imaging of diagnostic of recurrent cancer or undergoing surgical excision for presumed HNSCC.
• Adequate hematologic, hepatic function and end-organ function appropriate for surgical resection and anesthesia (within 30 days of infusion).
• Karnofsky performance status of at least 70% or Eastern Cooperative Oncology Group (ECOG)/Zubrod level 0-2.

Exclusion Criteria:

• Patients not planning for SOC surgical resection

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, HIV, 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:

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

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

  3. 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:

     1. Rash must cover < 10% of body surface area
     2. Disease is well controlled at baseline and requires only low-potency topical corticosteroids
     3. 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

• History of hepatitis C that has not been treated with curative intent.

• 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 on active systemic therapy.

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

• 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.

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

• Prior allogeneic stem cell or solid organ transplantation.

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

• 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:

  1. Patients who received acute, systemic immunosuppressant medication or a dose of systemic immunosuppressant medication are eligible for the study.
  2. 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.
  3. Patients with asthma that requires intermittent use of bronchodilators, inhaled steroids, or steroid injections may participate. Pulse oral steroids of ≤5 days is permitted if >30 days from first infusion.
  4. Patients using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate.
  5. Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.

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

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

We plan to post the results of this study and may share data upon request and proper agreements with other institutions.