PRINCETON, New Jersey, September 29, 2012 /PRNewswire/ --
- Long-Term Follow Up From Phase 3 Study (024) Demonstrated That 19.0 Percent of Treatment-Naïve Patients Who Received YERVOY at Investigational Dose of 10 mg/kg Plus Dacarbazine (DTIC) Were Alive at Four Years vs. 9.6 Percent of Patients Treated with DTIC Alone
- Few New Immune-Related Adverse Events Occurred Beyond Two Years of Treatment in Study 024
- Five-Year Follow Up from Three Exploratory Phase 2 Trials Add to Growing Body of Survival Data for YERVOY in Metastatic Melanoma
- In Both Analyses, Updated Survival Rates Remained Relatively Stable Over Time
Bristol-Myers Squibb Company today announced four- and five-year survival rates based on long-term follow up from Phase 3 and Phase 2 YERVOY® (ipilimumab) clinical trials in patients with treatment-naïve and previously-treated metastatic melanoma. The data were presented at the ESMO 2012 Congress (European Society for Medical Oncology). (Abstract #1127 and 1116.)
In the Phase 3 trial (024), patients who had not previously received treatment for metastatic melanoma (n=502) were randomized to receive either the investigational dose of YERVOY 10 mg/kg in combination with dacarbazine (DTIC, 850 mg/m) or DTIC alone. Long-term follow-up from this study demonstrated that treatment with YERVOY plus DTIC resulted in a four-year survival rate of 19.0% compared to 9.6% for DTIC alone. Additionally, the overall survival data appeared relatively stable between years three and four for patients treated with YERVOY plus DTIC (21.2% at three years and 19.0% at four years). The three and four-year survival rates for patients treated with placebo plus DTIC were 12.1% and 9.6%, respectively.
In three Phase 2 trials (007 [n=115], 008 [n=155] and 022 [n=217]) in which five-year follow-up data are available through a rollover study (025), patients received YERVOY at 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg. No comparator treatment arms were included in these studies. In treatment-naïve patients, the five-year estimated survival rates ranged from 38% to 49%, which was unchanged from the four-year rates. In previously-treated patients, the five-year estimated survival rates (12% to 28%) were relatively stable compared to the rates at four years (14% to 28%).
For patients who were alive after four years and who continue on therapy in study 024, few new immune-related adverse events occurred beyond two years of treatment. Overall safety data from these investigational studies have been previously presented. ,,, The types of adverse events (AEs) attributed to YERVOY in these studies were generally mechanism (immune)- based. YERVOY can result in severe and fatal immune-related adverse reactions due to T-cell activation and proliferation. Adverse events associated with YERVOY were managed with protocol-specific guidelines, including the administration of systemic corticosteroids, dose interruption/discontinuation and/or other immunosuppressants.
"Metastatic melanoma is one of the most aggressive forms of cancer with a historical five-year survival rate of less than ten percent in patients with distant metastasis. Results from these investigational studies showed a prolonged survival benefit with YERVOY at four and five years for some patients," said Celeste Lebbe, M.D., Professor of Dermatology, Hôpital Saint-Louis. "These results add to the growing body of long-term survival data seen in some patients treated with YERVOY and further our understanding of the potential of this immunotherapy in the treatment of metastatic melanoma."
About Study 024
Study 024 is a multi-national, randomized, double-blind Phase 3 study that evaluated the safety and efficacy of YERVOY (10 mg/kg) plus DTIC (850 mg/m) vs. DTIC alone in treatment naive patients with Stage III unresectable or Stage IV metastatic melanoma. Patients who received prior adjuvant therapy were allowed in the trial. Patients were randomly assigned in a 1:1 ratio to receive either YERVOY plus DTIC (n=250) or DTIC plus placebo (n=252) at Weeks 1, 4, 7, 10 followed by DTIC alone every 3 weeks through Week 22 (induction phase). If drug intolerance or progressive disease (PD) was noted during Weeks 12-24, treatment was discontinued. At Week 24, patients who had stable disease (SD) or an objective response (OR) during induction with no dose-limiting toxicity could enter a maintenance phase in which they received placebo or YERVOY every 12 weeks until PD, drug intolerance or end of study. The primary endpoint of study 024 was overall survival. Results from study 024, which included three-year follow-up data, were originally published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology Annual Meeting in 2011.
The combination of DTIC with YERVOY is not an FDA approved-regimen. In addition, study 024 was not designed to compare the safety and efficacy of the FDA-approved monotherapy dose of 3 mg/kg for unresectable or metastatic melanoma vs. the investigational dose of 10 mg/kg. Bristol-Myers Squibb is conducting a head-to-head Phase 3 study comparing the safety and efficacy of the currently-approved dose of 3 mg/kg vs. 10 mg/kg as monotherapy in patients with previously-treated or treatment naïve unresectable or metastatic melanoma. This study rapidly accrued patients and completed enrollment in just over four months.
About Study 025
Study 025 is a rollover Phase 2 study that includes patients from three trials who only received YERVOY: CA184-008, a single-arm study of YERVOY 10 mg/kg in previously treated patients (n=155); CA184-022, a dose-ranging study in which previously treated patients were randomized to receive YERVOY at 0.3 mg/kg (n=73), 3 mg/kg (n=72), or 10 mg/kg (n=72) with crossover from lower doses to 10 mg/kg allowed in patients whose disease progressed; and CA184-007, a randomized study of YERVOY 10 mg/kg with or without prophylactic budesonide in treatment-naïve (n=53) and previously treated patients (n=62). Treatment was administered every 3 weeks for up to four doses, at which point eligible patients could receive reinduction or maintenance YERVOY every 12 weeks starting at week 24. The analysis reported overall survival with updated last known alive date or death based on data collected through March 2012.
About Metastatic Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, 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. Some cancer cells can actively evade surveillance by the immune system, allowing tumors to survive. Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate is just 6 months with a 1-year mortality rate of 75%, making it one of the most aggressive forms of cancer. These rates are based on a meta-analysis of 42 Phase 2 trials of more than 2,100 previously-treated and treatment-naïve patients with Stage IV metastatic melanoma conducted by multiple cooperative groups from 1975-2005. The incidence of melanoma has been increasing for at least 30 years. The median age at diagnosis for melanoma is 57 and the median age at death is 67.
On 25March 2011, the US Food and Drug Administration (FDA) approved ipilimumab 3 mg/kg for the treatment of patients with unresectable (inoperable) or metastatic melanoma in the US. On 13 July 2011, the EU approved ipilimumab 3 mg/kg for the treatment of adult patients with previously-treated unresectable or metastatic melanoma.
YERVOY, which is a recombinant, human monoclonal antibody, is the first FDA-approved cancer immunotherapy that blocks the cytotoxic T- lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation.Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab's effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.
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About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the product described in this release will become commercially successful. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
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2. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 2010;11:155-164.
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4. Thomas L, Wolchok JD, Garbe C, et al. Safety of ipilimumab in patients (pts) with untreated, advanced melanoma alive beyond 2 years: Results from a phase III study. J Clin Oncol. 2012;30(15s): abstract 8512.
5. National Comprehensive Cancer Network (NCCN) Web site. "NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Melanoma." Available at: http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf Accessed on September 19, 2012.
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