PRINCETON, N.J. -- (BUSINESS WIRE) -- Bristol-Myers Squibb Company (NYSE: BMY) today announced updated survival data from the advanced melanoma cohort (n=107) of the expanded Phase 1b dose-ranging study of nivolumab, an investigational PD-1 immune checkpoint inhibitor, administered as a single agent (Study -003). Results showed sustained activity in this heavily pre-treated patient population as defined by two- and three-year survival rates of 48% and 41%, respectively, across dose cohorts. These data, which are based on Kaplan-Meier estimates, will be featured in an oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago on June 2 at 3 p.m. CDT (Abstract #9002).
“These Phase 1b results for nivolumab are encouraging in a group of patients with one of the most aggressive forms of cancer,” said F. Stephen Hodi, M.D., director of the Melanoma Treatment Center and director of the Center for Immuno-Oncology at Dana-Farber, and Associate Professor of Medicine at Harvard Medical School. “They represent the longest follow up data for survival in pre-treated advanced melanoma patients who have received an investigational PD-1 immune checkpoint inhibitor as a single agent.”
“We are committed to improving survival expectations for patients with advanced melanoma and to leading immuno-oncology research and development that adds to the treatment options for patients across lines of therapy and stages of disease,” said Michael Giordano, senior vice president, Head of Development, Oncology & Immunology. “The updated results reported in this Phase 1b study help to characterize the long-term survival of nivolumab in this patient population. We look forward to presenting additional follow up results at ASCO evaluating the combination regimen of nivolumab and Yervoy® (ipilimumab) in this tumor type along with the first reported results from a Phase 3 trial of Yervoy as an investigational adjuvant therapy.”
Results from Advanced Melanoma Cohort of Phase 1b Single Agent Study (-003)
Study -003 is a Phase 1b dose escalation study (n=306) evaluating the safety, antitumor activity and pharmacokinetics of nivolumab as a single agent in previously-treated patients with advanced melanoma (n=107), non-small cell lung cancer (NSCLC) (n=129), renal cell carcinoma (n=34), castration-resistant prostate cancer (n=17) or colorectal cancer (n=19). Based on an amendment to the protocol, patients were followed for survival. Eligible patients were administered nivolumab as an intravenous infusion every two weeks of each eight-week treatment cycle. Cohorts of three to six patients per dose level (0.1, 0.3, 1.0, 3.0 or 10 mg/kg) were enrolled sequentially. Patients continued treatment ≤2 years (12 cycles), unless they experienced complete response, unacceptable toxicity, progressive disease or withdrew consent.
Results from this study were initially presented in 2012 at ASCO and published in the New England Journal of Medicine. The initial and updated analysis is reflective of 107 previously-treated advanced melanoma patients who had not received prior treatment with Yervoy. Updated results reported here show sustained activity in heavily pre-treated patients as defined by two- and three-year survival rates of 48% and 41%, respectively, across dose cohorts. Of the 32% of patients with objective responses (based on RECIST criteria), the median duration of response was 22.9 months.
Safety data from this study published in the Journal of Clinical Oncology earlier this year, with all patients having greater than or equal to one year of follow up, demonstrated a spectrum, frequency and severity of treatment-related adverse events (AEs) that were consistent with those initially reported in the study in 2012. As reported, common drug-related AEs included fatigue (32%), rash (23%), diarrhea (18%) and pruritus (13%). Drug-related select AEs with potential immunologic etiologies, defined as adverse events that may require more frequent monitoring and/or unique intervention, included skin (36%), gastrointestinal (18%), endocrine (13%), hepatic (6.5%), pulmonary (3.7%) and renal (1.9%).
About Advanced 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. The incidence of melanoma has been increasing for at least 30 years. In 2012, an estimated 232,130 melanoma cases were diagnosed globally. Melanoma is mostly curable when treated in its early stages. However, in its late stages, the average survival rate has historically been just six months with a one-year mortality rate of 75%, making it one of the most aggressive forms of cancer.
About Bristol-Myers Squibb Immuno-Oncology Trials in Melanoma
Bristol-Myers Squibb is committed to the research and development of immuno-oncology as an innovative approach to treating melanoma and has a broad development program evaluating its approved and investigational immunotherapies – either as single agents or as part of a regimen - across lines of therapy, stages of disease and biomarker expression. Among these are five Phase 3 trials. There are two ongoing Phase 3 trials evaluating nivolumab as a single agent at the 3 mg/kg dose in treatment-naïve patients (CheckMate -066) as well as in patients who have been previously treated (CheckMate -037). A Phase 3 trial evaluating Yervoy 3 mg/kg vs. Yervoy 10 mg/mg in patients with previously treated or treatment-naïve metastatic melanoma is ongoing (Study -169) and the first results of a Phase 3 trial evaluating the use of Yervoy 10 mg/kg as adjuvant therapy among patients with Stage 3 melanoma who are at high risk of recurrence following complete surgical resection (Study -029) will be featured in an oral presentation at ASCO on June 2 at 3 p.m. CDT (Abstract #LBA9008). Additionally, a Phase 3 trial evaluating the combination regimen of nivolumab and Yervoy in treatment-naïve patients is ongoing (CheckMate -067).
About Nivolumab and Yervoy
Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Nivolumab and Yervoy are both monoclonal antibodies and immune checkpoint inhibitors, but target different receptors for distinct T-cell checkpoint pathways.
Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. We are investigating whether by blocking this pathway, nivolumab would enable the immune system to resume its ability to recognize, attack and destroy cancer cells.
Bristol-Myers Squibb has a broad, global development program to study nivolumab in multiple tumor types consisting of more than 35 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in non-small cell lung cancer (NSCLC) melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma. In 2013, the FDA granted Fast Track designation for nivolumab in NSCLC, melanoma and RCC.
Yervoy, which is a recombinant, human monoclonal antibody, 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 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.
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 severe 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:
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 the Bristol-Myers Squibb and Ono Pharmaceutical Partnership
Through a collaboration agreement with Ono Pharmaceutical in 2011, Bristol-Myers Squibb expanded its territorial rights to develop and commercialize nivolumab (BMS-936558/ONO-4538) globally except in Japan, Korea and Taiwan where Ono has retained all rights to the compound.
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, please 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 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 nivolumab will receive regulatory approval, that the combination use of nivolumab and Yervoy will receive regulatory approval, or that, if approved, 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.