Date: 2015-09-25
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 2015 European Cancer Congress (ECC2015)
Company: BMS (USA - NY) Ono Pharmaceutical (Japan)
Product: Opdivo® (nivolumab)
Action
mechanism: monoclonal antibody. Nivolumab is a 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 or metastatic (medically or surgically unresectable) clear-cell renal cell carcinoma
Therapeutic area: Cancer - Oncology
Country: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Norway, Poland, Romania, Russian Federation, Spain, Sweden, UK, USA
Trial
details: CheckMate -025 is a Phase 3 randomized, open-label study of Opdivo versus everolimus in previously treated patients with advanced clear-cell RCC after prior anti-angiogenic treatment. Patients were randomized to receive Opdivo (n=410) 3 mg/kg intravenously every two weeks or everolimus (n=411) 10 mg orally once daily. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), OS by PD-L1 expression, and incidence of adverse events (AEs). (NCT01668784)
Latest
news: * On September 25, 2015, BMS announced results from CheckMate -025, a Phase 3 study comparing Opdivo® to everolimus in advanced renal cell carcinoma (RCC) after prior anti-angiogenic treatment, showing a significant overall survival (OS) benefit for Opdivo®. In the trial, Opdivo® demonstrated a median OS benefit of 25 months compared to 19.6 months for everolimus. Clinical benefit for Opdivo® was observed regardless of level of PD-L1 expression. The safety profile shown in CheckMate -025 is consistent with previously reported Opdivo® trials. These data will be presented Saturday, September 26, during the 2015 European Cancer Congress (ECC2015) at a Presidential Session from 4:10 - 4:20 PM CEST (Late Breaking Abstract #3). The results were also featured during the ECC2015 press program on September 25 and published in The New England Journal of Medicine (NEJM), representing the ninth publication in the NEJM for Opdivo®. CheckMate -025 was stopped in July because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its primary endpoint, demonstrating superior OS in patients receiving Opdivo compared to the control arm. Opdivo was granted Breakthrough Therapy Designation for advanced RCC by the FDA based on results from this trial and the clinical need for additional treatment approaches for RCC. Results from CheckMate -025 mark the first and only Phase 3 study to demonstrate a significant survival advantage in previously treated patients with advanced RCC versus standard of care. Patients treated with Opdivo® in this study achieved a median OS of 25 months for Opdivo® and 19.6 months for everolimus (hazard ratio: 0.73; [98.5% CI, 0.57-0.93; p=0.0018]), with comparable OS benefit seen across PD-L1 expression levels. In addition to improving overall survival, Opdivo® demonstrated a superior ORR of 25% versus 5% for everolimus (p<0.0001), with one out of four patients experiencing a response. Seventeen percent of Opdivo® and 7% of everolimus patients remain on treatment with a minimum follow-up of 14 months. The safety profile of Opdivo® in CheckMate -025 was consistent with prior studies and favorable versus everolimus. Fewer grade 3-4 treatment-related AEs occurred with Opdivo® (19%) compared to everolimus (37%). Any grade treatment-related AEs occurred in 79% of patients treated with Opdivo and 88% of patients treated with everolimus. The most frequent treatment-related AEs were fatigue (33%), pruritus (14%), and nausea (14%) in the Opdivo® arm and fatigue (34%) and stomatitis (30%) in the everolimus arm. * On July 20, 2015, BMS announced that an open-label, randomized Phase III study evaluating Opdivo® (nivolumab) versus everolimus in previously-treated patients with advanced or metastatic renal cell carcinoma (RCC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo® compared to the control arm. The company looks forward to sharing these data with health authorities soon. CheckMate -025 investigators are being informed of the decision to stop the comparative portion of the trial. BMS is working to ensure that eligible patients will be informed of the opportunity to continue or start treatment with Opdivo® in an open-label extension as part of the company’s commitment to providing patient access to Opdivo, and characterizing long-term survival. The company will complete a full evaluation of the final CheckMate -025 data and work with investigators on the future presentation and publication of the results.
