Ipilimumab a powerful treatment option for previously treated skin disease

August 1, 2010

Results from a multicenter, randomized, phase 3 clinical trial represent a landmark in research for metastatic melanoma because they are the first ever to show an experimental agent significantly improving median and long-term overall survival in previously treated patients with unresectable stage III/IV disease, reported Steven O'Day, M.D., at the annual meeting of the American Society for Clinical Oncology.

Key Points

Chicago - Results from a multicenter, randomized, phase 3 clinical trial represent a landmark in research for metastatic melanoma because they are the first ever to show an experimental agent significantly improving median and long-term overall survival in previously treated patients with unresectable stage III/IV disease, reported Steven O'Day, M.D., at the annual meeting of the American Society for Clinical Oncology.

Overall survival

Secondary efficacy endpoints included comparison of median OS between the combination regimen and vaccine monotherapy groups and of best overall response rate (BORR), disease control rate (DCR) to week 24 and progression-free survival (PFS) comparing both ipilimumab-containing regimens versus vaccine-treated controls. For all of these endpoints, there were statistically significant benefits for the ipilimumab monotherapy and combination regimens.

The safety data reflected the potential for immune-related toxicity associated with ipilimumab, although adverse events with ipilimumab were generally mild and medically manageable, according to Dr. O'Day.

"These study results finally provide good news to the many researchers and clinicians who have faced disappointment for decades in treating a disease for which average survival is just six to nine months," he says. "The improvement in median survival associated with ipilimumab is impressive, but it is equally impressive that its benefit for improving survival appears to be persisting, with the longest available follow-up now out to 4.5 years."

Ipilimumab is a fully human monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4) that acts to potentiate T-cell activation. In extensive phase 2 study experience, which includes about 1,400 patients, ipilimumab was shown to provide durable disease control in about 20 to 30 percent of patients, and to improve two-year survival.

The gp100 vaccine was developed at the National Cancer Institute. It is an HLA-A*0201 restricted peptide vaccine that has been shown in clinical trials to produce T-cell specific immune responses, and when combined with IL-2, to improve response rate and PFS in metastatic melanoma.

MDX 010-20 is an international multicenter study conducted at 125 sites in 13 countries.

In addition to having been previously treated and having unresectable stage III/IV melanoma, patients had to be HLA-A*0201 positive. However, there were no exclusion criteria regarding pretreated CNS metastases or LDH level, Dr. O'Day says.

"The baseline characteristics for the study population showed that it was a very poor risk group with 70 percent of patients having M1c disease (visceral/non-lung metastases), almost 40 percent having elevated LDH, and 10 to 15 percent having been treated for CNS metastases," he says.