Stereotactic Ablative Radiotherapy (XRT) and Immunotherapy for Oligometastatic Extracranial Melanoma

Inclusion Criteria: * Female or male patients, age 18 or older * Willing to provide signed informed consent * Life expectancy \> 6 months * First presentation of AJCC Stage IV (any N, M1a, M1b, M1c), histologically confirmed cutaneous, acral or unknown primary melanoma with one to five extracranial metastases detected on CT and whole body PET-CT, and considered unresectable * A primary lesion and / or up to 4 in-transit metastases(is) (ITM) in addition to distant metastases(is) are permitted and will be counted in the maximum number of permitted baseline lesions * Prior surgery for symptomatic disease (e.g. small bowel obstruction) for this first presentation of Stage IV melanoma is permitted, provided the total number of remaining extracranial metastases is ≤ 5 (NOT including the resected lesion). No more than one excised metastatic lesion is permitted * At least one metastasis should be measurable as a target lesion per RECIST version 1.1 * No evidence of cerebral metastases on MRI brain (CT brain is acceptable if there is contraindication to MRI) * All lesions can be treated with a minimum SBRT biologically effective dose (BED) of 48Gy * Able to tolerate treatment with immunotherapy as determined by the medical oncologist * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of randomisation Exclusion Criteria: * Ocular or mucosal melanoma * Serious or unstable medical co-morbidities or other conditions that could interfere with the patient's safety, consent, or compliance * Patients for whom there is a definite and immediate indication for radiotherapy (e.g., spinal cord compression, rapidly progressing disease associated with clinical signs and symptoms) * Prior radiotherapy for Stage IV disease (prior adjuvant radiotherapy to primary site or nodal field (Stage I-III disease) is permitted, however adjuvant-treated sites must not be included in the baseline lesions * Inability to treat all disease sites with SBRT as determined by radiation oncologist * Prior systemic drug therapy for melanoma, unless given in the neoadjuvant or adjuvant setting for Stage I-III disease * Any contraindication to the planned standard of care immunotherapy regimen per regulatory approved product information * For patients with liver metastases - moderate/severe liver dysfunction * A known history of another malignancy or concurrent malignancy unless the patient is disease-free for a minimum of 1 year, is completely treated and is at low risk of recurrence * Pregnant or breastfeeding females