Study of Investigational Immuno-Oncology Agent Meets Primary Endpoint of Efficacy; Planning for Phase 3 Study Underway
Results to be Presented at 46th Annual Meeting of the American Society of Clinical Oncology
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol-Myers Squibb Company (NYSE: BMY) today announced positive results from a randomized Phase 2 study evaluating ipilimumab in combination with standard chemotherapy in previously untreated patients with advanced non-small cell lung cancer (NSCLC). The study, known as 041, met the predefined criteria for significant improvement (p-value of <0.1) in immune-related progression –free survival (irPFS), the primary endpoint, over chemotherapy alone. An additional analysis of progression-free survival (PFS), assessed using traditional mWHO criteria1, also reached statistical significance in one of the two dosing schedules that combined ipilimumab with standard chemotherapy. (Abstract #7531)
“Results from this Phase 2 study are very encouraging and support further investigation of ipilimumab in NSCLC in large scale Phase 3 trials,” said Dr. Thomas J. Lynch, Jr., director of Yale Cancer Center and physician-in-chief of the Smilow Cancer Hospital at Yale-New Haven. “As with melanoma, ipilimumab brings an innovative approach to lung cancer, which is very difficult to treat. These results add to our understanding of the potential of immuno-oncology in the treatment of cancer.”
Ipilimumab is a 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.
The 041 study evaluated two distinct regimens of ipilimumab in combination with a chemotherapy regimen that is commonly used to treat advanced NSCLC in the first-line setting compared to the same chemotherapy regimen given alone. The ipilimumab arms improved irPFS by approximately one month compared to the chemotherapy-only arm. Immune-related adverse events reported in the study included gastrointestinal, skin, liver, or endocrine systems.
Planning for a Phase 3 study of ipilimumab in the treatment of NSCLC is under way. Ipilimumab is an investigational compound and not currently approved for use by health authorities.
Immune-related PFS was 5.52 months (hazard ratio, 0.775; p=0.094), 5.68 months (hazard ratio, 0.686; p=0.026) and 4.63 months for the concurrent, phased and chemotherapy-alone groups, respectively. Progression-free survival as assessed by mWHO, a secondary endpoint, was 4.11 months (hazard ratio, 0.882; p=0.250), 5.13 months (hazard ratio, 0.691; p=0.024)) and 4.21 months for the concurrent, phased and chemotherapy-alone groups, respectively. Interim results for overall survival, also a secondary endpoint, were 11.01 months (hazard ratio, 0.962; p=0.429), 11.56 months (hazard ratio, 0.748; p=0.104) and 9.99 months for the concurrent, phased and chemotherapy-alone groups, respectively. Results for survival were based on an interim analysis and follow up continues.
Grade 3/4 adverse events (AEs) were 58%, 52% and 42% for the concurrent, phased and chemotherapy alone groups, respectively, and were reflective of previously reported events for these individual agents. The incidences of Grade 3/4 immune-related AEs were 20% and 15% for the concurrent and phased groups, respectively. 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 041 is a multi-center, randomized, double blind, three arm trial evaluating the efficacy and safety of ipilimumab in combination with paclitaxel/carboplatin compared to paclitaxel/carboplatin alone in previously-untreated patients with Stage IIIb or IV non-small cell lung cancer (n=203). The trial enrolled patients with squamous and non-squamous cell histology. Patients were randomized to receive ipilimumab (10 mg/kg every three weeks) concurrent with the first four cycles of chemotherapy (concurrent regimen), ipilimumab (10 mg/kg every three weeks) in combination with cycles three through six of chemotherapy (phased or sequential regimen) or chemotherapy alone. Ipilimumab was administered in a maintenance schedule (10 mg/kg every 3 months) after discontinuation of chemotherapy and until progression or undue toxicity in the former two treatment arms.
About Lung Cancer
In the U.S., more than 219,000 people were diagnosed with lung cancer in 2009, which accounts for about 15 percent of all cancer diagnoses. Non-small cell lung cancer makes up 85 percent of these cases, with many being diagnosed with locally advanced or metastatic disease. Lung cancer is the leading cause of cancer-related death in men and women, with more than 159,000 deaths occurring in 2009 – accounting for about 28 percent of all cancer deaths.
About Bristol-Myers Squibb
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 clinical trials described in this release will support a regulatory filing for ipilimumab for an indication in non-small cell lung cancer, that ipilimumab will receive regulatory approval or, if approved, that it will become a commercially successful product. 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, 2009, 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.
1 Modified World Health Organization criteria (mWHO) assess response in baseline lesions and stable disease with slow steady decline in total tumor burden.
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