- Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases. - Evidence of distant metastatic disease. - Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed. - History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example, cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease-free for > 5 years. - History or current evidence of cardiovascular risk. - History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).