Study of Avelumab and/or Radiation Therapy in People With Advanced Merkel Cell Carcinoma

Eligibility Criteria

• * Biopsy proven Merkel cell carcinoma which is unresectable or metastatic, stage III or IV
• * Prior first-line treatment with aPD1 monotherapy (defined as at least one dose of pembrolizumab, avelumab, nivolumab, etc.) with evidence of progression of disease ≥10 weeks after starting therapy, in the absence of significant clinical deterioration
• * Patients with clinical deterioration during aPD1 monotherapy are eligible ≥6 weeks after starting aPD1 therapy
• * Criteria for clinical deterioration to be determined and agreed upon by treating physician and Principal Investigator
• * All detectable sites of MCC are amenable to comprehensive ablative radiation therapy in opinion of treating radiation oncologist and principal investigator
• * ≥18 years of age
• * Performance status ≤2 on the Eastern Cooperative Oncology Group Performance Scale
• * Able to provide valid written informed consent
• * Normal organ and marrow function
• * Hematologic: Neutrophil count ≥1500/mm\^3, platelet count ≥100,000/mm\^3, hemoglobin ≥9 g/dL
• * Hepatic: Total bilirubin ≤ 1.5 times the upper limit of normal, unless Gilbert's syndrome; aspartate transaminase and alanine transaminase ≤ 2.5 times the upper limit of normal (in the absence of hepatobiliary metastases); ≤ 3.0 times the upper limit of normal (in the presence of hepatobiliary metastases)
• * Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula.
• * Prior systemic therapy for MCC other than first-line aPD1 monotherapy (ie, chemotherapy)
• * Pregnancy or breastfeeding
• * Adverse events due to prior cancer therapy which are grade 3 or higher and have not resolved
• * Prior severe hypersensitivity reaction (CTCAE version 5.0 grade ≥3) to avelumab
• * Prior radiotherapy which precludes the ability to safely deliver comprehensive ablative radiation therapy in the opinion of the treating radiation oncologist and principal investigator
• * Known central nervous system metastases
• * Known clinically significant cardiovascular disease, defined as:
• * Stroke or myocardial infarction within 6 months of first dose of avelumab
• * Symptomatic congestive heart failure (New York Heart Association Class 2 or higher)
• * Serious arrhythmia requiring anti-arrhythmic agents
• * Known Human Immunodeficiency Virus infection
• * Known Hepatitis B or C infection requiring ongoing treatment
• * Vaccination within 4 weeks of first dose of avelumab
• * Iatrogenic immunosuppression with daily systemic corticosteroid equivalent of \>10 mg of prednisone
• * Active autoimmune disease that may cause clinical deterioration during immunotherapy
• * Inflammatory bowel disease or immune colitis
• * Immune mediated pneumonitis or pulmonary fibrosis
• * History of solid organ or hematopoietic transplant
• * Active infection requiring systemic therapy
• * Active suicidal ideation or behavior
• * Comorbid or diagnostic abnormalities which would interfere with interpretation of study results
• * Known hematopoietic cancer or dysfunction (i.e., leukemia, lymphoma)
• * Known non-MCC solid tumor with known metastasis or estimated risk of metastasis \>20% within 3 months