- Across doses (n=107), 48% and 41% of this heavily pre-treated patient population that received nivolumab as a single agent was alive at two and three years, respectively
- Spectrum, frequency and severity of treatment-related adverse events from this study were consistent with those initially reported for these patients in prior publications
PRINCETON, NJ, USA I May 14, 2014 I 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.
SOURCE: Bristol-Myers Squibb
