Durable responses and long-term progression-free survival observed in a phase II study of MDX-010 alone or in combination with dacarbazine (DTIC) in metastatic melanoma

7525 Background: CTLA-4 is a negative regulator of cytotoxic T cell responses and may contribute to tumor escape from immune surveillance. MDX-010 is an IgG1κ fully human monoclonal antibody that blocks CTLA-4 function and is being studied in patients with metastatic melanoma and other malignancies. The current Phase II study was conducted to determine the safety and efficacy of MDX-010 when given alone or in combination with dacarbazine in chemotherapy and vaccine naïve patients with unresectable metastatic melanoma. Dacarbazine is an FDA approved agent for metastatic melanoma with an approximate 10% objective response rate (ORR) but no demonstrable survival benefit. Long-term follow-up data on response duration and median progression-free survival for this Phase II study is now reported. Methods: Patients were randomized to receive MDX-010 at 3 mg/kg monthly x 4 (arm A; n=37) or MDX-010 in combination with dacarbazine 250 mg/m2 for 5 days monthly x 4 (arm B; n=35). Clinical response was measured by RECIST at week 12 and patients were followed every 3 months until disease progression. Results: In Arm A there were 2 PRs (ORR 5%) and 4 SD. In Arm B there were 2 CRs and 4 PRs (ORR 17%) as well as 4 SDs. Long-term durable objective responses and disease stabilization have been observed in both monotherapy and combination arms of the study. In Arm A the 2 PRs are continuing at 11.9+ and 14+ months and 1 patient with SD is ongoing at 18.2+ months. In Arm B the 2 CRs are continuing at 12.6+ and 16.3+ months, and 1 PR is ongoing at 16.7+ months. The median progression-free survival in Arm A is 82 days and 99 days in Arm B. Conclusions: MDX-010 alone or in combination with dacarbazine can induce durable (i.e., greater than 1 year) objective clinical responses in previously untreated patients with metastatic melanoma. Furthermore, the ORR observed in patients treated with the combination of dacarbazine and MDX-010 appears higher than that reported with dacarbazine alone. The combination of dacarbazine plus MDX-010 merits further study in patients with metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medarex Medarex Medarex Medarex Medarex