Compassionate Program With Ipilimumab

Inclusion Criteria:

• Signed Written Informed Consent

• Histologically confirmed Stage III (unresectable) or Stage IV melanoma

• Must have failed at least one systemic therapy for malignant melanoma or beintolerant to at least one prior systemic treatment. Note: Enrollees must not beeligible for a clinical study with Ipilimumab

• Subjects with asymptomatic brain metastases are eligible

• Primary ocular and mucosal melanomas are allowed

• Must be at least 28 days since treatment with chemotherapy, biochemotherapy, orimmunotherapy, and recovered from any clinically significant toxicity experiencedduring treatment. Must have recovered from prior surgery or radiation. Systemiccorticosteroids should be eliminated or weaned to the minimum dose before startingIpilimumab treatment. - Consult with the Medical Monitor for individual subjects

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0- 2

• Life expectancy ≥ 16 weeks

• Subjects must have the complete set of baseline (screening/baseline) radiographicimages, including but not limited to brain, chest, abdomen, and pelvis. Bone scansshould be completed if clinically indicated. The images can be accepted if obtained 6weeks before initiation of Ipilimumab

• Required values for initial laboratory tests:

• White Blood Cells (WBC): ≥ 2000/uL (≥ 2 x 109/L)

• Antigen Neutrophil Count (ANC): ≥ 1000/uL (≥ 1 x 109/L)

• Platelets: ≥ 75 x 103/uL (≥ 75 x 109/L)

• Hemoglobin : ≥ 9 g/dL (≥ 80 g/L; may be transfused)

• Creatinine: ≤ 2.0 x ULN

• Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT):≤ 2.5 x Upper Limitof - Normal (ULN) for subjects without liver metastasis ≤ 5 times for livermetastases

• Bilirubin: ≤ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have atotal bilirubin of less than 3.0 mg/dL)

• Men and women, at least 16 years of age

• Prior treatment with an anti-Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4)drug is allowed provided therapy was not discontinued to to drug-related toxicity

• Women of childbearing potential (WOCBP) and their partners must use highly effectivemethods of birth control (double barrier, e.g, condom or diaphragm or cervical capassociated with spermicide or intrauterine device combined with another form of birthcontrol) for up to 12 weeks after the last dose of study drug to minimize the risk ofpregnancy

• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/Lor equivalent units of HCG) at Screening and within 24 hours prior to the start ofinvestigational product

• Women who are not of childbearing potential (i.e., who are postmenopausal orsurgically sterile

• Men of fathering potential must be using an adequate method of contraception to avoidconception throughout the study and for up to 12 weeks after the last dose ofinvestigational product in such a manner that the risk of pregnancy is minimized

• Payment of charitable contributions may be required

Exclusion Criteria:

• Women of Child-Bearing Potential (WOCBP) who are unwilling or unable to use anacceptable method to avoid pregnancy for the entire program and for up to 12 weeksafter the last dose of ipilimumab

• WOCBP using a prohibited contraceptive method

• Women who are pregnant or breastfeeding

• Womens with a positive pregnancy test are not enrollment

• Prior treatment with an anti CTLA 4 antibody if treatment failure was due toImmune-Related Adverse Events (irAEs) or discontinuation was due to an Adverse Event (AE)/Serious Adverse Event (SAE)

• Presence of known hepatitis B or hepatitis C (active) infection, regardless ofcontrol on antiviral therapy

• Any subject who has a life threatening condition that requires high-doseimmunosuppressants

• Subjects with melanoma who have another active, concurrent, malignant disease, withthe exception of adequately treated basal or squamous cell skin cancer, superficialbladder cancer, or carcinoma in situ of the cervix

• Any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks before or after any dose of Ipilimumab, with the exceptions of Amantadine andFlumadine

• Any subject enrolled in a registrational study (ie, CA184-024) that has a survival asa primary endpoint should not be enrolled in CA184-045.

• Subjects from studies CA184-042, CA184-078 or CA184-087, who are being followed forsurvival only or for scans only are not eligible for this program

• Therapy with dexamethasone (corticosteroid) must be completed for 1 month prior toattending the program

• Current or planned participation in a study of an investigational agent or using aninvestigational device.

• Has received systemic immunosuppressive treatments within 6 months of start of studydrug

• Requires treatment with high dose systemic corticosteroids within 4 weeks of start ofstudy drug.

• Has received prior interstitial brachytherapy, implanted chemotherapy, stereotacticradiosurgery or therapeutics delivered by local injection or convection enhanceddelivery.

• Requires therapeutic anticoagulation with warfarin at baseline; patients must be offwarfarin or warfarin-derivative anti-coagulants for at least 7 days prior to startingstudy drug; however, therapeutic or prophylactic therapy with low-molecular weightheparin is allowed.

• Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan otherthan those that are grade ≤ 1 and either post-operative or stable on at least 2consecutive MRI scans.

• Has gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade > 3within 6 months of start of study drug.

• Has a known additional malignancy that is progressing or requires active treatmentwithin 3 years of start of study drug. Exceptions include basal cell carcinoma of theskin, squamous cell carcinoma of the skin, or in situ cervical cancer that hasundergone potentially curative therapy.

• Has an active autoimmune disease requiring systemic treatment within the past 3months or a documented history of clinically severe autoimmune disease, or a syndromethat requires systemic steroids or immunosuppressive agents.

• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

• Has an active infection requiring systemic therapy.

• Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Has known active Hepatitis B or Hepatitis C in the acute form of the disease.

• Has received a live vaccine within 30 days prior to the first dose of study drug.

• Has a known hypersensitivity to any of the study therapy products.

• Has a history of non-healing wounds or ulcers, or bone refractures within 3 months offracture.

• Has a history of arterial thromboembolism within 12 months of start of study drug.

• Has inadequately controlled hypertension.

• Has a history of hypertensive crisis or hypertensive encephalopathy

• Has had clinically significant cardiovascular disease within 12 months of start ofstudy drug.

• Positive result of the analysis of BRAF mutations.(mandatory testing for BRAF andNRAS mutations before).

• Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominalabscess within 6 months prior to start of study drug.