Three Phase II Ipilimumab Studies Showed Almost Half Of Previously Treated Metastatic Melanoma Patients Alive Beyond One Year

Main Category: Melanoma / Skin Cancer
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 18 Sep 2008 - 1:00 PDT

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Bristol-Myers Squibb announced updated survival data from three Phase II studies of ipilimumab in patients with advanced metastatic melanoma (Stage III or IV), which showed that approximately half of previously-treated patients who received ipilimumab (10 mg/kg) remained alive beyond one year. 1,2,3 Ipilimumab is designed to block the activity of CTLA-4 (a molecule on T-cells that plays a critical role in regulating natural immune responses), and thereby activates the immune system to fight metastatic melanoma.4,5

The results are based on a follow-up of the patient population from studies 008, 022 and 007. 47 - 51 percent of patients with advanced metastatic melanoma treated with 10 mg/kg of ipilimumab (induction and maintenance) showed a consistent survival rate of one-year.1,2,3 Specifically, the results show:

- 47 percent of patients who had progressed while on or after receiving standard treatment achieved one year survival (Study 008)1
- 48 percent of patients who were previously treated, relapsed or failed to respond to experimental treatment or were unable to tolerate currently approved therapies achieved one-year survival (Study 022)2
- 51 percent of patients previously treated with therapy other than ipilimumab achieved one year survival (Study 007)3

Recent medical literature, based on a meta-analysis of 42 Phase II trials with 2,100 patients, reported a one-year survival rate of approximately 25.5 percent for patients with Stage III or IV metastatic melanoma, the most advanced type of the disease.6

In the UK, more than 9,500 cases of metastatic melanoma are diagnosed and 1,800 people die of the disease every year.7It is the most-progressive form of skin cancer and occurs when cancer spreads beyond the surface of the skin to other organs, such as the lymph nodes, lungs, brain or other areas of the body.8 Metastatic melanoma accounts for 10 percent of all skin cancers and is the primary cause of death from skin cancer.9

"Currently, there are few treatment options available for patients with advanced melanoma," said Michele Maio, M.D., Ph.D. Director, Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy. "As these data on ipilimumab continue to mature, we are encouraged by the durability of response and consistency of survival results observed across all three Phase II studies."

Ipilimumab is being developed through a joint partnership between Bristol-Myers Squibb and Medarex (Nasdaq: MEDX), a biopharmaceutical company, in the United States.

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 presence of CTLA-4 suppresses the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, and thereby activates the immune system to fight metastatic melanoma. 4,5

About studies 008, 022 and 007

The three studies enrolled a total of 487patients across North America, Europe, South America, Africa and Australia with Stage III or Stage IV metastatic melanoma treated with 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg of 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.1,2,11 M1c disease can also be associated with an elevated level of lactate dehydrogenase (LDH) and is typically indicative of the worst prognosis.10 Specifically, the three Phase II monotherapy trials include:

- A Phase II open-label, single arm trial (008) evaluating overall response rate in 155 patients who progressed while on or after receiving standard treatment1

- A Phase II randomised, 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 who were unable to tolerate currently approved therapies2

- A Phase II randomised, double-blind trial (007) evaluating the rate of grade 2+ diarrhoea in 115 patients receiving ipilimumab with or without prophylactic oral budesonide3

The primary endpoint of studies 008 and 022 was best overall response rate and the primary endpoint of study 007 was to compare the rate of grade 2+ diarrhoea in patients receiving ipilimumab with or without prophylactic oral budesonide. 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 007.1,2,3

Safety results from the three studies showed that the most common immune-related adverse events (greater than five percent) were rash, diarrhoea and hepatitis, as well as endocrinopathies (four percent); the grade 3 and 4 immune-related adverse event rates were approximately 20 - 29 percent and zero to 12 percent respectively in patients who received 10 mg/kg of ipilimumab.1,2,11 Adverse events were generally manageable and reversible with the use of established treatment guidelines in the majority of patients. 2,3,11

About BMS

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. http://www.bms.com

References

1. Maio.M et al. Efficacy and Safety of Ipilimumab in Patients with Advanced Melanoma Who had Progressed on One or More Prior Therapies: Results from a Single-Arm, Multicenter Study. European Society for Medical Oncology 2008. Poster no. 776PD. 15 September 2008. (Study 008)

2. Lebbe. C et al. Effect of Dose on Efficacy and Safety in Ipilimumab-treated Patients with Advanced Melanoma: Results from a Phase II, Randomized, Dose-ranging Study. European Society for Medical Oncology 2008. Oral Presentation No. 769O. 15 September 2008. (Study 022)

3. Ridolfi. R et al. Efficacy and Safety of Treatment Naïve and Previously Treated Patients with Advanced Melanoma Receiving Ipilimumab. European Society for Medical Oncology 2008. Poster no. 778PD. 15 September 2008. (Study 007)

4. Cranmer LD & Hersh E. The role of the CTLA4 blockade in the treatment of malignant melanoma. Cancer Invest 2007;25(7):613-31

5. Gabriel EM & Lattime EC. Anti-CTL-associated antigen 4: are regulatory T cells a target? Clin Cancer Res 2007;13(3):785-8

6. Korn, E. "Meta-analysis of Phase 2 Cooperative Group Trials in Metastatic Stage IV Melanoma to Determine Progression-Free and Overall Survival Benchmarks for Future Phase 2 Trials." Journal of Clinical Oncology. 26 (4).526-534. 2008

7. Cancer Research UK. UK malignant melanoma incidence statistics. Available online at: http://info.cancerresearchuk.org/cancerstats/types/skin/?a=5441 [Accessed 9 September 2008]

8. American Cancer Society Web site. "How Is Melanoma Diagnosed?" Available here. [Accessed 9 September 2008]

9. National Institute for Health and Clinical Excellence. Improving outcomes for people with skin tumours including melanoma: the manual. Available online here. Accessed 9 September 2008

10. e-Medicine. Malignant Melanoma. January 2008. Available here. [Accessed 9 September 2008]

11. Ron. I et al. Efficacy and Safety of Patients with Advanced Melanoma Treated with Ipilimumab with or without the Addition of Prophylactic Budesonide. European Society for Medical Oncology 2008. Poster Presentation No. 783P. 13 September 2008. (Study 007)

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