Positive results from Phase 3 trial of ipilimumab in patients with metastatic melanoma

Bristol-Myers Squibb Company (NYSE: BMY) today announced positive results from a Phase 3 randomized, double blind study of ipilimumab which demonstrated that overall survival (OS) was significantly extended in patients with previously-treated metastatic melanoma who received ipilimumab. The results were statistically significant for patients receiving ipilimumab alone (hazard ratio 0.66,>

“Results from this ipilimumab study are exciting and show the potential of harnessing the immune system to treat cancers like metastatic melanoma”

As in other studies of ipilimumab, the most common side effects reported in the study were immune-related and based on the mechanism of action. These immune-related adverse events were sometimes severe and life-threatening, and most often affected the gastrointestinal, skin, liver, or endocrine systems.

The data were published today in the New England Journal of Medicine and presented at the 46^th Annual Meeting of the American Society of Clinical Oncology. (Abstract # 4)

"Metastatic melanoma is one of the deadliest forms of cancer with no approved options for pre-treated patients," said Steven J. O'Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California, and presenter of the study results. "For the first time, a significant improvement in overall survival has been demonstrated in previously-treated advanced melanoma patients in a large, randomized Phase 3 study."

"Results from this ipilimumab study are exciting and show the potential of harnessing the immune system to treat cancers like metastatic melanoma," said F. Stephen Hodi, M.D., Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute and lead author on the New England Journal of Medicine paper.

Ipilimumab is a novel T-cell potentiator that specifically blocks the inhibitory signal of CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. Suppression of CTLA-4 can augment the immune system's T-cell response in fighting disease.

Ipilimumab is an investigational compound and is not currently approved for use by health authorities. Bristol-Myers Squibb is in discussions with health authorities worldwide and expects to submit applications for regulatory approval of ipilimumab in advanced melanoma this year.

Study Results

In this study, median OS was 10, 10.1 and 6.4 months for the ipilimumab + gp100, ipilimumab alone and gp100 alone groups, respectively. The hazard ratios of the ipilimumab + gp100 group and the ipilimumab alone group relative to gp100 monotherapy are 0.68 and 0.66 with corresponding p-values of 0.0004 and 0.0026, respectively. At one year, 44-46% of patients treated with ipilimumab were alive compared to 25% of patients treated with gp100 alone. At two years, 22-24% of patients treated with ipilimumab were alive compared to 14% of patients treated with gp100 alone.

Grade 3/4 drug-related adverse events (AEs) were observed in 17%, 23% and 11% of the ipilimumab + gp100, ipilimumab and gp100 arms, respectively. Grade 3/4 immune-related AEs (irAEs) were seen in 10-15% of the ipilimumab treatment arms and 3% in the gp100 alone arm. Fourteen drug-related deaths (2.1%, 3.1% and 1.5% of the ipilimumab + gp100, ipilimumab and gp100 arms, respectively) occurred in the study, with seven (1.3%, 1.5% and 0%, of the ipilimumab + gp100, ipilimumab and gp100 arms, respectively) attributed to an irAE. Immune-related adverse events were treated with the use of supportive care and systemic steroids using established protocol-specific treatment guidelines.

SOURCE Bristol-Myers Squibb Company