New Monoclonal Antibody Treatment Offers Hope for Treatment of Metastatic Melanoma

CHICAGO—A human monoclonal antibody that blocks a receptor that down regulates T-cell responses improves long-term survival in patients with previously treated advanced melanoma, according to the results of a phase 3 trial.

“This is the first time we have shown a survival benefit in metastatic melanoma,” said Steven O’Day, MD, lead investigator of the study, and chief of research and director of the melanoma program at The Angeles Clinic and Research Institute in Los Angeles. “What is equally impressive is the near doubling in the 1-year and 2-year landmark overall survival analyses.”

The study was a head-to-head comparison of treatments in 676 patients with previously treated, unresectable stage III or IV melanoma. There were three treatment arms: monotherapy with ipilimumab (n = 137), gp100 peptide vaccine alone (n = 136), and the combination of these two agents (n = 403).

Ipilimumab is a fully human monoclonal antibody that blocks the CTLA-4 receptor (CTLA-4 is an antigen found on T cells that downregulates the T-cell response) and potentiates T-cell activation. gp100 is a vaccine that produces T-cell–specific immune responses, and served as the active control arm for this study.

“By blocking CTLA-4, ipilimumab keeps the T-cell potentiated and hopefully leads to antitumor immunity,” O’Day explained.

Patients in both ipilimumab arms achieved improvements in overall survival. In the gp100 vaccine plus placebo group, median overall survival was 6.4 months, which is comparable with results with placebo in previous studies. In each of the two arms receiving ipilimumab, median overall survival was 10.0 months.

One-year survival was 44% in patients who received combination treatment with ipilimumab plus vaccine, and 46% in those treated with ipilimumab alone, compared with 25% in the gp100 vaccine group. Two-year survival was 22% and 24%, respectively, compared with 14% in patients in the vaccine group.

Better disease control was also seen in both groups treated with ipilimumab. After 6 months, melanoma progression was halted in approximately 30% of patients, compared with only 11% of those who received the gp100 vaccine alone.

Serious adverse events were more common in both ipilimumab arms, at 17.4% and 22.9%, respectively, compared with 11.4% in the gp100 plus placebo arm.

Of significance are the side effects with ipilimumab related to the immune system. These occurred in two thirds of the ipilimumab arm patients and in only one third of the gp100 vaccine group. In ipilimumab-treated patients, T cells began attacking normal tissue at sites, the most common being dermatologic, gastrointestinal, endocrine, and hepatic tissue.

“Ipilimumab represents a new class of T4 potentiators, and an important advance for the field of immunooncology,” O’Day said. “Further development of ipilimumab is ongoing. We are very interested in looking at alternative combinations with this drug, as well as in refining its dosage and schedule.”