Published: June 05, 2010

The Angeles Clinic and Research Institute Announces Investigational Compound Ipilimumab Demonstrates Improved Overall Survival in Phase 3 Trial of Previously-Treated Patients with Metastatic Melanoma

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LOS ANGELES - (BUSINESS WIRE) - Los Angeles-based The Angeles Clinic and Research Institute 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 Angeles Clinic and Research Institute was a key site and played a leadership role in the clinical trial, which was sponsored by Bristol-Myers Squibb.

The data were presented by The Angeles Clinic's Steven J. O'Day, M.D., at the 46^th Annual Meeting of the American Society of Clinical Oncology (Abstract #4). In addition, the data were published today in the New England Journal of Medicine, co-lead author by Dr. O'Day. Dr. O'Day is Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, based in Los Angeles, California. The study will be presented at ASCO's prestigious plenary session on Sunday June 6.

"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."

The results were statistically significant for patients receiving ipilimumab alone (hazard ratio 0.66, p=0.0026) or ipilimumab in combination with a gp100 peptide vaccine (hazard ratio 0.68, p=0.0004) when compared to those patients who received the control therapy of gp100 alone. Forty-four to 46 percent of patients treated with ipilimumab were alive at one year compared to 25 percent of patients treated with the control arm. At two years, 22 to 24 percent of patients treated with ipilimumab were alive compared to 14 percent of patients treated with the control arm.

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.

"Results from this ipilimumab study are exciting and show the potential of harnessing the immune system to treat cancers like metastatic melanoma," said Steven J. O'Day, M.D.

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.

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.

About the Study

Study 020 is a randomized, double-blind global Phase 3 study of patients with unresectable Stage III or IV metastatic melanoma who have received prior therapies and were HLA-A2+. HLA-A2+ is a group of proteins that play a role in the body's immune system and the gp100 vaccine used as the comparator in study 020 is specific for patients who are HLA-A2+ .

Eligible patients were randomized to receive ipilimumab + gp100 (3 mg/kg and 1mg/kg every three weeks for four doses; n=403), ipilimumab (3 mg/kg every three weeks for four doses) + placebo (n=137), or gp100 + placebo (n=136). There was no maintenance dosing phase. The primary endpoint was comparison of OS between patients who received ipilimumab + gp100 vs. gp100 alone. The secondary endpoints were an OS comparison of ipilimumab alone vs. gp100, progression free survival (PFS), best objective response rate (BORR) at Week 24, disease control rate (DCR) and safety. Re-induction was allowed within 28 days of documented progression, provided the patient had not experienced any dose limiting toxicities and response to the initial cycle of therapy was stable disease lasting â‰¥3 months from the first tumor assessment at Week 12, or complete response, or partial response. Patients in the study were re-induced with 1 to 3 additional courses of the originally assigned regimen in 7.2%, 6.5% and 1% of ipilimumab + gp100, ipilimumab and gp100 arms, respectively.

About Advanced Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. As with many cancers, it is more difficult to treat once the disease has spread beyond the skin to other parts of the body by way of the bloodstream or the lymphatic system (metastatic disease). Melanoma accounts for about three percent of skin cancer cases, but it causes more than 80% of skin cancer deaths.

According to the World Health Organization, approximately 132,000 new cases of melanoma are diagnosed each year globally. The incidence of melanoma has increased ten-fold over the past 50 years, and has steadily increased since the 1970s. The American Cancer Society estimates that in 2009, there were 68,720 new cases of melanoma in the U.S.

About The Angeles Clinic and Research Institute

For more information about The Angeles Clinic and Research Institute, please visit http://www.theangelesclinic.org