Disease control and long-term survival in chemotherapy-naive patients with advanced melanoma treated with ipilimumab (MDX- 010) with or without dacarbazine
9022 Background: Ipilimumab is a fully human monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) that gave durable complete/partial responses [CR/PR] and stable disease [SD]) in previously treated patients with advanced melanoma. The current study evaluated the safety and efficacy of ipilimumab and whether adding dacarbazine (DTIC) would improve outcome. In addition to being cytotoxic, DTIC may also increase the release of tumor neo-antigen, ie, act as an immunosupportive (Peggs et al. Cancer Cell.12:192, 2007) agent. Methods: Chemotherapy-naive patients with advanced melanoma were treated in the randomized, phase II, comparative, multicenter, open-label study MDX-010–08 (first patient, first visit September 2002; last patient, last visit August 2004). Patients received 3 mg/kg ipilimumab every 4 weeks (Q4W) X 4 alone or with up to six 5-day courses of DTIC 250 mg/m2 per day. Efficacy was determined using Response Evaluation Criteria for Solid Tumors. Overall survival data was collected. Results: Seventy-two patients were randomized, treated per protocol, and eligible for analysis (ipilimumab, n = 37; ipilimumab + DTIC, n = 35). The disease control rate (best response of CR + PR + SD) was 21.6% (n = 8) and 31.4% (n = 11) in the monotherapy and combination arms, respectively. In 6 of these 19 patients, disease control lasted ≥24 weeks, including 2 ongoing CRs in the combination arm lasting 40+ and 92+ weeks. Long-term data are available for 54/72 patients: 5/54 patients (9.3%) are still alive (ipilimumab, n = 2/19 [10.5%]; ipilimumab + DTIC, n = 3/27 [11.1%]). The median OS for all patients was 368.5 days [95% CI, 276 - 472]; for the monotherapy and combination groups, respectively, the median OS was 351 [95% CI, 208 - 596] and 386 [95% CI, 253 - 571] days. Updated data will be presented. Conclusions: At least ∼10% of chemotherapy-naive patients with advanced melanoma treated with ipilimumab ± DTIC were alive after 2 to >4 years of follow up. DTIC appeared to augment ipilimumab efficacy. A study is ongoing to determine if ipilimumab administered at 10 mg/kg Q3W X 4 followed by maintenance therapy with DTIC will further improve the efficacy of this combination.