The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma.
2007 ASCO Annual Meeting
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 8523
Author(s):
J. S. Weber, E. M. Hersh, M. Yellin, G. M. Nichol, W. Urba, J. D. Powderly, S. J. O'Day
Abstract:
Background: Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), enhances antitumor immune responses resulting in durable objective responses. In this study we examined the efficacy and safety of different ipilimumab preparations and regimens in patients with unresectable metastatic melanoma.
Methods: In this study (MDX010-15), 34 patients received either 2.8 or 5 mg/kg transfectoma- or 3 mg/kg hybridoma-derived ipilimumab on days 1, 57 and 85. Additionally, 30 patients received single doses of 7.5 (6 pts), 10 (7 pts), 15 (6 pts) or 20 mg/kg (11 pts) transfectoma-derived ipilimumab. Once single doses up to 20 mg/kg were found to be well tolerated, 24 additional patients were given up to 4 doses of 10 mg/kg ipilimumab on days 1, 22, 43 and 64. Complete or partial responses (CR, PR), stable disease (SD) and adverse events (AEs) were monitored.
Results: 1 CR, 3 PRs and 10 durable SDs were confirmed in 88 treated patients at the time of analysis. ORs were durable (~29+, 34, 38+ and 39+ weeks [w]) and ongoing in 3 patients at study completion. PR in 1 patient was observed after ~18.5w and developed to an ongoing CR at ~51w. In another, SD for ~16w preceded a ~30w+ PR. Durable SD ranged from ~21 to 79+w and is ongoing in 4 patients. Patients with OR or SD had immune-related AEs including rash, pruritis (G1/2), diarrhea (G1/2/3) or colitis (G2). AEs were severe in 27 patients, and considered ipilimumab-related (mostly G3/G4 colitis and diarrhea) in 9 (10% of all treated patients).
Conclusions: Preliminary results suggest ipilimumab is generally safe and well tolerated. Late-onset ORs can occur, sometimes preceded by months of SD. ORs and SDs tend to be durable. Drug-related AEs of an immune nature are probably related to the biologic effects of ipilimumab, and are similar to those reported previously. No obvious dose relationship to AEs has been seen to date. |
