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

Inclusion 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 progression in only one of several responding metastases will not be eligible
  • 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: Lymphocyte count ≥800/mm^3, neutrophil count ≥1500/mm^3, platelet count ≥75,000/mm^3, leukocyte count ≥3000/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.

Exclusion Criteria:

• 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

  °Patients with prior grade 3 or higher immune related adverse events are not eligible, even if they have 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

  °Institutional guidelines for reirradiation will be used when making this determination

• 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

  °Inactivated vaccines are permissible

• Iatrogenic immunosuppression with daily systemic corticosteroid equivalent of >10 mg of prednisone

• Active autoimmune disease that may cause clinical deterioration during immunotherapy

  °Including, but not limited to:

• 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