Date: 2014-05-14
Type of
information: Results
phase: 1b
Announcement: results of the first part of the study
Company: BMS (USA - NY)
Product: nivolumab
Action
mechanism:
- monoclonal antibody/immune checkpoint inhibitor. 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. PD-1, a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. Opdivo® is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. Opdivo® is the world’s first approved drug targeting PD-1.
- This monoclonal antibody has been generated under a research collaboration entered into in May 2005 between Ono and Medarex. When Medarex was acquired by BMS in 2009, it also granted BMS its rights to develop and commercialize the anti-human PD-1 monoclonal antibody in North America. Through the collaboration agreement entered into in September 2011 between Ono and BMS, Ono granted BMS exclusive rights to develop and commercialize Opdivo® in the rest of the world, except in Japan, Korea and Taiwan where Ono has retained all rights to develop and commercialize the compound.
Disease: advanced melanoma
Therapeutic
area: Cancer - Oncology
Country:
Trial
details:
- 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.
Latest
news:
- • On May 14, 2014, BMS 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). 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%).
Is
general: Yes
