Clinical Trials

Date: 2017-04-03

Type of information: Presentation of results at a congress

phase: 1b

Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting

Company: BMS (USA - NY)

Product: Opdivo® (nivolumab)

Action mechanism: monoclonal antibody. 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: previously treated advanced non-small cell lung cancer

Therapeutic area: Cancer - Oncology

Country: USA

Trial details: CA209-003 (NCT00730639) is a Phase 1b, open-label, multicenter, multidose, dose-escalation study of Opdivo® in patients with select advanced or recurrent malignancies, including previously treated non-small cell lung cancer (NSCLC). In this study, patients received one to five prior systemic therapies for advanced NSCLC (n=129) and were treated with Opdivo® (1, 3 or 10 mg/kg) intravenously once every two weeks for less than 96 weeks. The primary objectives were measures of safety and tolerability. Secondary objectives include antitumor activity. Overall survival (OS) and analysis by PD-L1 expression levels were exploratory objectives. (NCT00730639)

Latest news:

• • On April 3, 2017, BMS announced the first report of five-year overall survival (OS) data from the Phase 1 dose-ranging study CA209-003 evaluating Opdivo® in patients with previously treated advanced non-small cell lung cancer (NSCLC; n=129). Overall survival was an exploratory endpoint in this study. The estimated OS rate at five years was 16% in heavily pre-treated NSCLC patients; survival was observed across PD-L1 expression levels and tumor histologies. At five years, the estimated OS rate for patients treated with Opdivo at all doses was 16%, and the median OS was 9.9 months (95% CI: 7.8, 12.4), with a minimum follow-up of 58 months. The five-year OS rates were consistent across histologies (squamous = 16% [n=54]; non-squamous = 15% [n=74]). In patients with evaluable PD-L1 expression (n=68/129), five-year OS rates increased as the PD-L1 expression level increased. Five-year OS rates were 20%, 23% and 43% in patients with PD-L1 expression <1%, ?1% and ?50%, respectively. PD-L1 status was not evaluable in 47% of patients (n=61/129); the estimated five-year OS rate in patients with unknown PD-L1 status was 10%. Based on investigators’ assessment, 75% (n=12/16) of patients remained without evidence of progressive disease at their last follow-up. In the study, five-year survivors had variable length of time and disease course from diagnosis to Opdivo treatment initiation. The median time from initial diagnosis to start of Opdivo was 1.2 years (range, 0.4 to 6.1 years).
• These data were featured during the official press program at the American Association for Cancer Research (AACR) Annual Meeting 2017 in Washington, D.C.
• Scott N. Gettinger, M.D., a senior author of CA209-003 and associate professor of medicine, Yale Cancer Center, New Haven, Conn., commented, “Historically, five-year survival rates for patients with advanced NSCLC have been less than 5%. With new data emerging from the NSCLC cohort of CA209-003, we observe that the estimated five-year overall survival rate in Opdivo-treated patients in the study was 16%. In addition, based on investigator assessments, the majority of these patients showed no evidence that their lung cancer had progressed at the time of their last follow-up. These findings offer important new insights into the long-term clinical profile of Opdivo in this patient population.”

 

Is general: Yes