Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma

Inclusion

Patients with metastatic melanoma who have measurable disease
ECOG PS 0 or 1
Adequate bone marrow function
WBC >= 3,000
Hgb >= 9
Plt >= 100
Adequate hepatic function, defined by the following parameters:
Total bilirubin WNL unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin =< 2 x ULN
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN unless associated with hepatic metastases, then ALT and AST =< 5 x ULN
Signed, written informed consent

Exclusion

Previous treatment with any other compound that targets CD40 or CTLA4
Concurrent treatment with any anticancer agent outside of this protocol
Prior allogeneic bone marrow transplant
History of brain metastases, even if previously treated
History of autoimmune disorder, including type 1 diabetes mellitus, pemphigus vulgaris, systemic mastocytosis, systemic lupus erythromatosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjorgen's syndrome, vasculitis/arteritis, Behcet's syndrome, autoimmune thyroiditis, multiple sclerosis, or uveitis
History of chronic inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis or enterocolitis of any etiology
History of diverticulitis (even a single episode) or evidence at baseline, including evidence limited to CT scan only. Note diverticulosis is not an exclusion criterion per se.
History (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, congestive heart failure
History of deep venous thrombosis or migratory thrombophlebitis (Trousseau)
Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand's disease, or cancer-associated DIC)
Prior allergic reactions attributed to other monoclonal antibodies
Concurrent or planned concurrent treatment with systemic high dose (immunosuppressive) corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline
Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial
Concurrent or planned concurrent treatment with anticoagulants such as Coumadin or heparin, except to maintain patency of in-dwelling catheters
Ongoing or active infection; treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed)
Pregnancy or breast-feeding; female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy and for 12 months following the last dose of either tremelimumab or CP-870,893; all female patients with reproductive potential must have a negative pregnancy test prior to enrollment
Other uncontrolled, concurrent illness that would preclude study participation; or, psychiatric illness or social challenges that would entail unreasonable risk or preclude informed consent or compliance with study procedures