
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from a Phase 3 randomized, double blind study demonstrating that Yervoy (ipilimumab) 10 mg/kg (n=475) significantly improved recurrence-free survival (RFS, the length of time before recurrence or death) vs. placebo (n=476) for patients with stage 3 melanoma who are at high risk of recurrence following complete surgical resection, an adjuvant setting. A twenty-five percent reduction in the risk of recurrence or death was observed (HR = 0.75; 95% CI = 0.64–0.90; p = 0.0013). At three years, an estimated 46.5% of patients treated with Yervoy were free of disease recurrence compared to an estimated 34.8% of patients on placebo. The median RFS was 26.1 months for Yervoy vs. 17.1 months for placebo, with a median follow-up of 2.7 years. The data will be presented at the 50th Annual Meeting of the American Society of Clinical Oncology at 3:00 p.m. CDT today and highlighted at a Congress press briefing (LBA9008).
Treatment-related adverse events were common, with most being immune-related, and were managed using standard Yervoy adverse event (AE) management protocols. These Grade ≥3 AEs in the Yervoy and placebo arms, respectively, were gastrointestinal (15.9% vs. 0.8%), liver (10.6% vs. 0.2%), endocrine (8.5% vs. 0%) and dermatologic (4.5% vs. 0%). Most were managed and resolved using established algorithms. Per investigator assessment, the incidence of drug-related death in the Yervoy arm was 1.1% (n=5) and no drug-related deaths were observed in the placebo arm. Of the patients who began treatment with Yervoy (n=471), 48.8% (n=230) discontinued treatment due to drug-related AEs vs. 1.7% (n=8) in the placebo arm.
“Despite the strong likelihood of disease recurrence among stage 3 melanoma patients, there are very limited treatment options available to help reduce the risk of metastatic disease after surgery. There is only one class of therapies available to patients and this standard of care has remained largely unchanged over the last 20 years,” said Alexander Eggermont, director general, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France, presenter of the results and lead author of the abstract. “These findings are significant not only because ipilimumab is the first immune-checkpoint inhibitor to demonstrate an improvement in recurrence-free survival in this earlier treatment setting, but also because this benefit was observed across all patient sub-groups, including those who were at highest risk of recurrence. These findings add to the growing body of data for ipilimumab, which is currently approved at 3 mg/kg for metastatic melanoma.”
“This is the third positive Phase 3 trial of Yervoy in melanoma, reflecting our commitment to seeking options to address unmet medical needs across stages of disease and lines of therapy for melanoma,” said Michael Giordano, senior vice president, Head of Development, Oncology & Immunosciences, Bristol-Myers Squibb. “These findings demonstrate, for the first time, that Yervoy has the potential to reduce the risk of cancer recurrence at an earlier stage of melanoma and support our belief that immuno-oncology may have broad applicability across lines of therapy and stages of the disease.”
Additional trials of Yervoy for melanoma in the adjuvant setting are ongoing, including a Phase 3 study sponsored by the U.S. National Cancer Institute and conducted by ECOG-ACRIN investigating Yervoy at doses of 3 mg/kg and 10 mg/kg, or high-dose interferon alfa-2b in patients with high-risk stage 3 and resectable stage 4 melanoma.
About Study -029
CA184-029 (EORTC 18071) is a randomized, double-blind Phase 3 trial sponsored by Bristol-Myers Squibb and conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC), assessing the efficacy of Yervoy at the investigational dose of 10 mg/kg in preventing or delaying recurrence after complete resection of high-risk Stage 3 melanoma. The trial enrolled patients in the United States, Canada, Europe, Russia and Australia who underwent complete resection of stage 3 cutaneous melanoma, excluding lymph node metastasis ≤1 millimeter or in-transit metastasis. Patients had stage 3A (21%), 3B (45%) or 3C (35%) melanoma; 41% percent had ulcerated primary melanoma and 56% had macroscopic lymph node involvement. Patients were stratified by stage and region and were randomized 1:1 to receive Yervoy 10 mg/kg (n=475) or placebo (n=476) every 3 weeks for 4 doses, then every 3 months for up to 3 years until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival, analyzed on the intent-to-treat population.
Adjuvant Therapy in Melanoma
Melanoma is separated into five staging categories (stages 0-4) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes.
Stage 3 melanoma has reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized), and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy, although adjuvant treatment options are very limited. Despite surgical intervention and possible adjuvant treatment, most patients experience disease recurrence and progress to metastatic disease. By five years, the majority of stage 3B and 3C patients (68% and 89%, respectively) and a third of stage 3A patients (37%) have experienced disease recurrence.
About Yervoy
Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy 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 Yervoy’s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries.
There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. This includes Phase 3 trials in prostate and lung cancers.
YERVOY® (ipilimumab) INDICATION & IMPORTANT SAFETY INFORMATION
YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma.
Important Safety Information
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs) and thyroid function tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic high-dose corticosteroids for sever immune-mediated reactions.
Recommended Dose Modifications
Withhold dose for any moderate immune-mediated adverse reactions or for symptomatic endocrinopathy until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5 mg prednisone or equivalent per day.
Permanently discontinue YERVOY for any of the following:
Immune-mediated Enterocolitis:
Immune-mediated Hepatitis:
Immune-mediated Dermatitis:
Immune-mediated Neuropathies:
Immune-mediated Endocrinopathies:
Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:
Pregnancy & Nursing:
Common Adverse Reactions:
Please see Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions, available at www.bms.com.
YERVOY® is a registered trademark of Bristol-Myers Squibb Company.
Immuno-Oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease. To address this unmet medical need, Bristol-Myers Squibb is leading advances in a rapidly evolving field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer. This includes conducting research on the potential of combining immuno-oncology agents that target different and complementary pathways in the treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.
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. For more information about Bristol-Myers Squibb, visit www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. 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 of Yervoy for the investigational uses described in this release will support regulatory filings, or that the investigational uses of Yervoy described in this release will lead to additional approved indications, or, if approved, that they 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, 2013 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.