Bristol-Myers Squibb Company and Medarex, Inc. today announced preliminary survival data for ipilimumab (10 mg/kg monotherapy), an investigational oncology immunotherapy, in previously-treated patients with advanced metastatic melanoma
PRINCETON, NJ, USA | June 01, 2008 | Bristol-Myers Squibb Company (NYSE: BMY) and Medarex, Inc. (NASDAQ: MEDX) today announced preliminary survival data for ipilimumab (10 mg/kg monotherapy), an investigational oncology immunotherapy, in previously-treated patients with advanced metastatic melanoma.
Results of three Phase 2 studies (008, 022 and 007) and one Phase 1/2 study (MDX010-15), presented at the 44th Annual Meeting of the American Society of Clinical Oncology, showed:
* One-year projected survival rate of 46.7 percent and median overall survival of 10.2 months in patients who had progressed while on or after receiving standard treatment (Study 008, Abstract #9021);
* One-year projected survival rate of 53.4 percent and median overall survival of 14.6 months 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 #9025);
* One-year projected survival rate of 59.1 percent in treatment-naïve patients and patients previously treated with therapy other than ipilimumab—at the time of analysis, the median overall survival had not been reached (Study 007, Abstract # 9010); and
* Two-year projected survival rate of 30 percent and median overall survival of 13.4 months in heavily pre-treated melanoma patients (Study MDX010-15, Abstract #3018).
The median follow-up for survival in studies 008, 022 and 007 was 9.5, 8.9 and 10.9 months, respectively. The median follow-up for survival in study MDX010-15 was 15.5 months.
“Prolonging survival is the ultimate goal of any cancer treatment,” said Steven J. O’Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California. “These ipilimumab studies are particularly important when you consider that the recent medical literature reports median overall survival of six to nine months and a one-year survival rate of 25 to 35 percent for patients with Stage III or Stage IV metastatic melanoma. The ipilimumab data offer further insight into the potential role of harnessing the immune system to fight cancer.”
The four studies enrolled a total of 510 patients with Stage III or Stage IV metastatic melanoma treated with 10 mg/kg ipilimumab therapy. Approximately half of the patients in each of the trials had stage M1c disease, which indicates that melanoma metastases have spread to internal organs. M1c disease can also be associated with an elevated level of serum LDH and is typically indicative of the worst prognosis. Overall survival, one-year survival rates, disease control rate, stable disease and other measurements of anti-tumor activity and patterns of responses were secondary endpoints in studies 008, 022 and 007. Long-term survival data from study MDX010-015 was collected in a separate follow-up study (MDX010-28).
Additional data presented from studies 008, 022 and 007, which further demonstrated the potential clinical activity of ipilimumab at the 10 mg/kg dosing regimen, included:
* A statistically significant relationship between increased response rate and increased dose (p=0.0015) in study 022, favoring the 10 mg/kg regimen, as determined by independent radiology review (IRC); and
* Disease control rates (proportion of patients with complete responses, partial responses or stable disease) of 27.1 percent (42 of 155), 29.2 percent (21 of 72) and 35.1 percent (20 of 57) across studies 008, 022 and 007, respectively.
Investigators also discussed unique patterns of response observed in studies 008, 022 and 007, which suggested that conventional criteria for classifying short-term response and tumor progression may not accurately capture the clinical activity observed with ipilimumab. For example, an exploratory analysis utilizing endpoints that assessed total tumor burden showed that some patients who received 10 mg/kg of ipilimumab can initially demonstrate progression of the target lesion or new lesions but subsequently go on to achieve responses. In these patients, both the initial lesion and new lesions shrank in size or resolved with additional follow-up. The resulting response rates observed by the investigators using the exploratory analyses may correlate better with the survival data presented (Abstracts #3008 and #3020).
“Ipilimumab involves immune activation that begins early and builds an immune response over time,” said F. Steven Hodi, M.D., Clinical Director of the Melanoma Program at Dana-Farber Cancer Institute. “The ipilimumab data observed show patterns of response that are different from conventional chemotherapy and underscore the need for criteria that more accurately describe clinical activity and long-term benefit.”
Safety results from the four studies were generally consistent with data from previously reported clinical trials of ipilimumab. The most common immune-related adverse events (greater than five percent) were rash, diarrhea and hepatitis, as well as endocrinopathies (four percent). The high-grade (3/4) immune-related adverse event rate was approximately 20 to 40 percent in patients who received 10 mg/kg of ipilimumab. The adverse events were generally manageable and reversible within days or weeks with the use of systemic steroids and established treatment guidelines in the majority of patients.
About the Studies
The four studies enrolled patients across North America, Europe, South America and Africa and included:
* A Phase 2 open-label, single arm trial (008) evaluating overall response rate in 155 patients who progressed while on or after receiving standard treatment;
* A Phase 2 randomized, double-blind trial (022) evaluating the efficacy of three dose levels of ipilimumab in 217 patients who were previously treated, relapsed or failed to respond to experimental treatment or were unable to tolerate currently approved therapies; and
* A Phase 2 randomized, double-blind trial (007) in 115 patients comparing the safety of ipilimumab, with prophylactic oral budesonide or placebo (primarily evaluating the rate of grade 2+ diarrhea).
* A Phase 1/2 trial (MDX010-15) evaluating the efficacy of the 10 mg/kg dosing regimen in 23 highly-refractory melanoma patients treated with ipilimumab.
The primary endpoint of studies 008 and 022 was best overall response rate and the primary endpoint of study 007 was to compare the safety of ipilimumab with or without prophylactic oral budesonide. Top-line results from these studies were previously announced. The primary endpoint of study MDX010-15 was to determine the safety and pharmacokinetic profile of single and multiple doses of ipilimumab.
About Ipilimumab
Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system’s T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.
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 most skin cancer deaths. The American Cancer Society estimates that in 2008 there will be 62,480 new cases of melanoma in the U.S., and about 8,420 people will die of this disease.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb® technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. More than 40 of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with seven of the most advanced product candidates currently in Phase 3 clinical trials or the subject of regulatory applications for marketing authorization. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world’s unmet healthcare needs. For more information about Medarex, visit its Web site at www.medarex.com.
SOURCE: Bristol-Myers Squibb Company
Post Views: 75
Bristol-Myers Squibb Company and Medarex, Inc. today announced preliminary survival data for ipilimumab (10 mg/kg monotherapy), an investigational oncology immunotherapy, in previously-treated patients with advanced metastatic melanoma
PRINCETON, NJ, USA | June 01, 2008 | Bristol-Myers Squibb Company (NYSE: BMY) and Medarex, Inc. (NASDAQ: MEDX) today announced preliminary survival data for ipilimumab (10 mg/kg monotherapy), an investigational oncology immunotherapy, in previously-treated patients with advanced metastatic melanoma.
Results of three Phase 2 studies (008, 022 and 007) and one Phase 1/2 study (MDX010-15), presented at the 44th Annual Meeting of the American Society of Clinical Oncology, showed:
* One-year projected survival rate of 46.7 percent and median overall survival of 10.2 months in patients who had progressed while on or after receiving standard treatment (Study 008, Abstract #9021);
* One-year projected survival rate of 53.4 percent and median overall survival of 14.6 months 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 #9025);
* One-year projected survival rate of 59.1 percent in treatment-naïve patients and patients previously treated with therapy other than ipilimumab—at the time of analysis, the median overall survival had not been reached (Study 007, Abstract # 9010); and
* Two-year projected survival rate of 30 percent and median overall survival of 13.4 months in heavily pre-treated melanoma patients (Study MDX010-15, Abstract #3018).
The median follow-up for survival in studies 008, 022 and 007 was 9.5, 8.9 and 10.9 months, respectively. The median follow-up for survival in study MDX010-15 was 15.5 months.
“Prolonging survival is the ultimate goal of any cancer treatment,” said Steven J. O’Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California. “These ipilimumab studies are particularly important when you consider that the recent medical literature reports median overall survival of six to nine months and a one-year survival rate of 25 to 35 percent for patients with Stage III or Stage IV metastatic melanoma. The ipilimumab data offer further insight into the potential role of harnessing the immune system to fight cancer.”
The four studies enrolled a total of 510 patients with Stage III or Stage IV metastatic melanoma treated with 10 mg/kg ipilimumab therapy. Approximately half of the patients in each of the trials had stage M1c disease, which indicates that melanoma metastases have spread to internal organs. M1c disease can also be associated with an elevated level of serum LDH and is typically indicative of the worst prognosis. Overall survival, one-year survival rates, disease control rate, stable disease and other measurements of anti-tumor activity and patterns of responses were secondary endpoints in studies 008, 022 and 007. Long-term survival data from study MDX010-015 was collected in a separate follow-up study (MDX010-28).
Additional data presented from studies 008, 022 and 007, which further demonstrated the potential clinical activity of ipilimumab at the 10 mg/kg dosing regimen, included:
* A statistically significant relationship between increased response rate and increased dose (p=0.0015) in study 022, favoring the 10 mg/kg regimen, as determined by independent radiology review (IRC); and
* Disease control rates (proportion of patients with complete responses, partial responses or stable disease) of 27.1 percent (42 of 155), 29.2 percent (21 of 72) and 35.1 percent (20 of 57) across studies 008, 022 and 007, respectively.
Investigators also discussed unique patterns of response observed in studies 008, 022 and 007, which suggested that conventional criteria for classifying short-term response and tumor progression may not accurately capture the clinical activity observed with ipilimumab. For example, an exploratory analysis utilizing endpoints that assessed total tumor burden showed that some patients who received 10 mg/kg of ipilimumab can initially demonstrate progression of the target lesion or new lesions but subsequently go on to achieve responses. In these patients, both the initial lesion and new lesions shrank in size or resolved with additional follow-up. The resulting response rates observed by the investigators using the exploratory analyses may correlate better with the survival data presented (Abstracts #3008 and #3020).
“Ipilimumab involves immune activation that begins early and builds an immune response over time,” said F. Steven Hodi, M.D., Clinical Director of the Melanoma Program at Dana-Farber Cancer Institute. “The ipilimumab data observed show patterns of response that are different from conventional chemotherapy and underscore the need for criteria that more accurately describe clinical activity and long-term benefit.”
Safety results from the four studies were generally consistent with data from previously reported clinical trials of ipilimumab. The most common immune-related adverse events (greater than five percent) were rash, diarrhea and hepatitis, as well as endocrinopathies (four percent). The high-grade (3/4) immune-related adverse event rate was approximately 20 to 40 percent in patients who received 10 mg/kg of ipilimumab. The adverse events were generally manageable and reversible within days or weeks with the use of systemic steroids and established treatment guidelines in the majority of patients.
About the Studies
The four studies enrolled patients across North America, Europe, South America and Africa and included:
* A Phase 2 open-label, single arm trial (008) evaluating overall response rate in 155 patients who progressed while on or after receiving standard treatment;
* A Phase 2 randomized, double-blind trial (022) evaluating the efficacy of three dose levels of ipilimumab in 217 patients who were previously treated, relapsed or failed to respond to experimental treatment or were unable to tolerate currently approved therapies; and
* A Phase 2 randomized, double-blind trial (007) in 115 patients comparing the safety of ipilimumab, with prophylactic oral budesonide or placebo (primarily evaluating the rate of grade 2+ diarrhea).
* A Phase 1/2 trial (MDX010-15) evaluating the efficacy of the 10 mg/kg dosing regimen in 23 highly-refractory melanoma patients treated with ipilimumab.
The primary endpoint of studies 008 and 022 was best overall response rate and the primary endpoint of study 007 was to compare the safety of ipilimumab with or without prophylactic oral budesonide. Top-line results from these studies were previously announced. The primary endpoint of study MDX010-15 was to determine the safety and pharmacokinetic profile of single and multiple doses of ipilimumab.
About Ipilimumab
Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system’s T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.
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 most skin cancer deaths. The American Cancer Society estimates that in 2008 there will be 62,480 new cases of melanoma in the U.S., and about 8,420 people will die of this disease.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb® technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. More than 40 of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with seven of the most advanced product candidates currently in Phase 3 clinical trials or the subject of regulatory applications for marketing authorization. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world’s unmet healthcare needs. For more information about Medarex, visit its Web site at www.medarex.com.
SOURCE: Bristol-Myers Squibb Company
Post Views: 75
