Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON).

-INCLUSION CRITERIA:

• Histologically or cytologically confirmed recurrent or metastatic olfactory neuroblastoma (ONB) not amenable to potentially curative local therapies. Review of tissue samples by Pathology at the National Institutes of Health (NIH) is preferred.
• Participants must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. A previously treated lesion by radiotherapy can be chosen as the target lesion only if progression in the respective lesion has been demonstrated during or following radiotherapy.
• Participants should have received at least one line of systemic therapy including a platinum agent, with evidence of disease progression clinically or radiographically.
• Men or Women >=18 years of age on day of signing informed consent. Because no dosing or adverse event data are currently available on the use of bintrafusp alfa in participants =1,500/mcL
• Hemoglobin >=9 g/dL (transfusions allowed)
• Platelets >=100,000/mcL
• Serum Creatinine =30 mL/min/1.73m^2 for participant with creatinine levels > 1.5 x institutional ULN
• Serum total bilirubin 1.5 x ULN
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) = 200 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman's disease within 12 months prior to enrollment.
• For participants with serological evidence of chronic hepatitis B virus (HBV) infection, the HBV deoxyribonucleic acid (DNA) viral load must be undetectable on suppressive therapy, if indicated.
• For participants with serological evidence of hepatitis C virus (HCV) infection, the HCV ribonucleic acid (RNA) viral load must be negative to be eligible for study participation.
• Ability of participant to understand and the willingness to sign a written informed consent document.
• Must co-enroll in the following two studies. A separate inform consent will be obtained from participant for these studies.
• 21-C-0009: A Natural History Study of Children and Adults with Olfactory Neuroblastoma, and
• 18-DC-0051: Biospecimen procurement for NIDCD clinical protocols

EXCLUSION CRITERIA

• Anticancer treatment, concurrent or prior (chemotherapy, monoclonal antibody, cytokine therapy, immune therapy, targeted small molecule therapy) or any investigational drug, within 4 weeks or 5 half-lives (whichever shorter) prior to the first drug administration. All residual treatment-related toxicities must have resolved or be minimal and not constitute a safety risk. Note: Palliative radiotherapy is permitted concurrently or within the pretreatment period. Subjects receiving bisphosphonates or denosumab are eligible provided treatment was initiated at least 14 days before treatment.
• Participants who received prior checkpoint blockade therapy and were taken off treatment for serious adverse events related to immuno-therapy are excluded.
• Major surgery within 4 weeks prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).
• Active or prior documented autoimmune or inflammatory diseases that might deteriorate on immunostimulatory agent (including colitis or Crohn's disease, systemic lupus erythematosus, sarcoidosis, vasculitis, Grave's disease, hypophysitis, uveitis, rheumatoid arthritis etc.), except the following:
• Type I diabetes mellitus
• Chronic skin conditions that do not require systemic therapy (including eczema, vitiligo, alopecia, psoriasis)
• Hypothyroidism (e.g., post-Hashimoto thyroiditis) stable, on hormone replacement
• Mild autoimmune disease not active in the last 5 years may be eligible after consultation with the principal investigator.
• Current use of immunosuppressive medication within 14 days before the first dose of the study medication, except the following:
• Intranasal,