Targeted Therapy and Avelumab in Merkel Cell Carcinoma

Inclusion Criteria: * Patient is 18 years of age or older and who has provided written informed consent. * Patient has histologically confirmed metastatic MCC. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 . * Willing and able to comply with all study protocol requirements for the duration of the study. * Patient must have measurable disease by CT or MRI per RECIST version 1.1 criteria. * Patient is treatment naïve (no prior systemic therapy for unresectable or metastatic MCC). Note that prior chemotherapy is permitted in the adjuvant setting for loco-regional disease. Prior radiation is permitted for treatment of the primary or loco-regional disease. * At least 2 weeks since the completion of prior therapy, including surgery or radiotherapy. * Screening laboratory values, obtained within 14 days prior to registration/randomisation must meet the criteria specified in the protocol. * Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception * WOCBP must have a negative serum or urine pregnancy test within within 7 days prior to the start of avelumab treatment and should be performed every 4 weeks in line with other safety bloods or clinical reviews. * Male patients who are sexually active with a WOCBP must use any contraceptive method with a failure rate of less than 1% per year. * Patient must be agreeable to have archival tumour material collected Exclusion Criteria: * Patient is excluded if they have ever had any brain or leptomeningeal metastases. * Prior exposure to immune checkpoint inhibitors (e.g. anti-CTLA-4, anti-PD-1/PD-L1/PD-L2, etc.) or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. * Prior exposure to 177Lu-DOTATATE. * Prior malignancy within the previous 2 years, except for locally curable cancers that have been apparently cured (e.g. basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, colon, bladder or breast). * Life expectancy of 6 months or less. * An active, known or suspected autoimmune disease that might lead to clinically significant deterioration as per the investigator when receiving an immunostimulatory agent. Patients are permitted to enrol if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. They are permitted to enrol if they have clinically quiescent auto-immune conditions not requiring immunomodulation beyond low dose steroids (ie \<10mg per day of prednisolone or equivalent) or topical therapies (including mesalazine or steroid enemas). * Current use of immunosuppressive medication, with exceptions detailed in the protocol * Prior organ transplantation, including allogeneic stem-cell transplantation. * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). * Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory hepatitis C virus (HCV) RNA (if anti-HCV antibody tested positive at Screening). * Pregnant or breastfeeding. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. * Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on Investigator's judgement are acceptable. * Known prior severe hypersensitivity to investigational product or any component in its formulations, including known hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade 3). * Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable. * Use of any live vaccines against infectious diseases (e.g., influenza, varicella, etc.) within 30 days of registration.