The FINANCIAL — Bristol-Myers Squibb Company (NYSE: BMY) and Medarex, Inc. (NASDAQ: MEDX) on May 31 announced updated survival results from follow-up extensions of three Phase 2 ipilimumab studies of patients with advanced metastatic melanoma (Stage III or IV).
The two-year survival rate ranged from 29.8 to 41.8 percent in patients who received ipilimumab (10 mg/kg). Results of the survival data were presented at the 45th Annual Meeting of the American Society of Clinical Oncology in Orlando, FL., May 29 – June 2, 2009.
The results are based on follow-up of up to 37.5 months (median follow-up ranging from 10.1 to 16.3 months) of the patient population from studies 008, 022 and 007 treated with 10 mg/kg of ipilimumab (induction and maintenance) and, specifically, showed:
Two-year survival rate of 32.8 percent (95% CI: 25.37%- 40.49%) in patients who had progressed while on or after receiving standard treatment (Study 008, Abstract #9033);
Two-year survival rate of 29.8 percent (95% CI: 19.13%- 41.14%) in patients who were previously treated, relapsed or failed to respond to experimental treatment or were unable to tolerate currently approved therapies (Study 022, Abstract #9033);
Two-year survival rate of 40.6 percent (95% CI: 27.12%- 54.37%) and 41.8 percent (95% CI: 28.30%- 55.46%) in patients receiving ipilimumab plus budesonide or ipilimumab plus placebo, respectively, which included treatment-naïve patients and patients previously treated with therapy other than ipilimumab (Study 007, Abstract #9033).
Historical melanoma survival rates from previous clinical trials have been estimated by a recent meta-analysis of 42 Phase 2 trials of over 2,100 patients with Stage III or IV metastatic melanoma indicating that, at one year, approximately 25 percent of patients were alive. Results from three separately published randomized Phase 3 studies using dacarbazine as the control arm reported that, at two years, approximately 8 to 12 percent of metastatic melanoma patients were alive.
The updated survival analyses did not include additional safety data. As previously reported, safety results include follow-up of up to 16.3 months with a median follow-up ranging from 4.7 to 5.65 months. The most common immune-related adverse events were rash, diarrhea and hepatitis. Grade 3 and 4 immune-related adverse event rates were approximately 20 to 29 percent and zero to 12 percent, respectively, in patients who received 10 mg/kg of ipilimumab. Adverse events were managed with the use of supportive care and systemic steroids using established treatment guidelines in the majority of patients. Additionally, the use of systemic steroids to manage adverse events does not appear to diminish or impact the clinical effect of ipilimumab (Abstract #9037).
“The ongoing survival data observed with ipilimumab are encouraging, particularly because the advanced melanoma patient population currently has limited treatment options,” said Steven J. O’Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California. “The potential of ipilimumab is also underscored by the fact that we can report two-year survival results from these studies involving a significant number of metastatic melanoma patients.”
Candidate Biomarkers of Ipilimumab
Researchers also presented an exploratory analysis from four Phase 2 ipilimumab studies (008, 022, 007 and 004) that looked at the association between clinical activity and multiple potential biomarkers, including the change in absolute lymphocyte count (ALC) in melanoma patients after they received ipilimumab (Abstracts #9008 and #3020). ALC is a measure of the number of immune cells in circulation.
In a combined analysis of studies 007, 008 and 022, clinical activity was associated with an increase in the rate of change in ALC. Patients with clinical activity had a higher average increase in ALC over time than did patients without clinical activity (P=0.0013) and no patient with a decrease in ALC over time had clinical activity. This association was separately confirmed in Study 004. Increases in ALC following administration of ipilimumab were also significantly associated with dose (studies 007, 008, 022: P<0.0001; study 004: P=0.0015), favoring the 10 mg/kg regimen. Based on these early biomarker findings, further research to explore the implication of ALC and other potential biomarkers of clinical activity of ipilimumab continues.
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