The study consists of two treatment regimens, both of which are administered as intravenous infusions. In the concurrent regimen (n=53), eligible patients received nivolumab and Yervoy every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses. Combined treatment was subsequently continued every 12 weeks for up to 8 doses. Cohorts of a maximum of seventeen patients per dose level (0.3 mg/kg nivolumab + 3 mg/kg Yervoy; 1 mg/kg nivolumab + 3 mg/kg Yervoy; 3 mg/kg nivolumab + 1 mg/kg Yervoy; 3 mg/kg nivolumab + 3 mg/kg Yervoy) were enrolled. In the sequenced regimen (n=33), patients previously treated with Yervoy received nivolumab alone every 2 weeks. Cohorts of six patients per dose level (1, 3 mg/kg) were enrolled. After completion of therapy, patients without confirmed disease progression were followed for 2.5 years. Patients with initial disease control and subsequent disease progression could be retreated with the original regimen. Initial disease control was defined as complete response, partial response, or stable disease for greater than or equal to24 weeks. All cohorts were enrolled in sequence from each other.
Two Distinct Immune Checkpoint Inhibitors
Nivolumab and Yervoy are both immune checkpoint inhibitors, but they are monoclonal antibodies that target different receptors for distinct T-cell checkpoint pathways.
Nivolumab is an investigational, fully-human IgG4 anti-PD-1 receptor blocking monoclonal antibody that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T cells. Nivolumab inhibits the binding of PD-1 with its tumor-expressed ligands, programmed death-ligand 1 (PD-L1/B7-H1) and PD-L2 (B7-DC). Blocking of the interaction of the PD-1 receptor with its ligands may allow T-cells to elicit an anti-tumor immune response.
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 25 March 2011, the US Food and Drug Administration (FDA) approved ipilimumab 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. In July 2011, the EU approved ipilimumab 3 mg/kg for the treatment of adult patients with previously-treated unresectable or metastatic melanoma. Yervoy is now approved in 41 countries.
For full Prescribing Information, please refer to the SMPC.[1]
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.
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 basedon 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 the late-stage clinical trials described in this release will support regulatory filings, 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, 2012, 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.
Reference
1) Yervoy Summary of Product Characteristics. July 2011. Available at:
http://www.ema.europa.eu/ema/index.jsp?c...
Last accessed June 2013.
Contacts:
Media: Elzbieta Zawislak, +48-608-55-55-89 elzbieta.zawislak@bms.com
Investors: Ranya Dajani, +1-609-252-5330, ranya.dajani@bms.com ; Ryan Asay,
+1-609-252-5020, ryan.asay@bms.com
