A phase II, randomized multi-center study of MDX-010 alone or in combination with dacarbazine (DTIC) in stage IV metastatic malignant melanoma

7511 Background: MDX-010 is a human anti-CTLA-4 IgG1 monoclonal antibody that blocks CTLA-4 and augments immune responses. In stage IV melanoma patients MDX-010 given with a gp100 vaccine demonstrated responses that correlated with autoimmune toxicity (Autoimmune Breakthrough Events; ABEs). The current study determined the safety and activity of MDX-010 alone or with dacarbazine in Stage IV melanoma. Methods: 76 patients were enrolled and 72 received drug. Patients were randomized to receive MDX-010, 3 mg/kg monthly × 4 (arm A; n=37) or MDX-010 in combination with dacarbazine 250 mg/m2 for 5 days monthly × 4 (arm B; n=35). Responses were determined after 4 treatments. Results: The study arms were well balanced. ABEs were noted as follows. There were five Grade III ABEs in arm A; colitis (n=2), uveitis (n=2) and rash (n=1). There were six Grade III/IV ABEs in arm B; Grade III diarrhea/colitis (n=2), Grade III rash (n=2), Grade III increased ALT (n=1), and Grade IV hypersensitivity reaction (n=1). All ABEs ...