Study of Radiotherapy Administered in Combination With Ipilimumab in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma

Inclusion Criteria:

* Willing and able to give written informed consent.
* Histologic diagnosis of melanoma.
* Unresectable locally advanced or metastatic melanoma with at least one melanoma metastasis accessible to radiation therapy.
* Measurable disease according to immune related Response Criteria
* Required values for initial laboratory tests:

WBC \>= 2000/uL ANC \>= 1000/uL Platelets \>= 75 x 103/uL Hemoglobin \>= 8 g/dL Creatinine \<= 2,5 x ULN AST/ALT \<= 2.5 x ULN for patients without liver metastasis or \<= 5 x ULN for patients with liver metastasis Total Bilirubin \<= 1,5.x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

* No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
* ECOG Performance status of 0 or 1.
* Men and women, \>= 18 years of age.
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

* Suspected or known CNS tumors including brain metastasis.
* Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
* Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
* Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
* Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
* A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
* Concomitant hormonal treatment, chemotherapy or immunotherapy.
* Other investigational therapy.
* Prior radiotherapy within the same body area.
* Prior radiotherapy targeting fields containing flat bones.
* Women of childbearing potential (WOCBP), defined above
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
* Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped.