Type of information: Clinical research agreement
Compound: Adcetris® (brentuximab vedotin) and Opdivo® (nivolumab)
Company: BMS (USA - NY) Seattle Genetics (USA - WA)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: antibody drug conjugate (ADC)/monoclonal antibody/immune checkpoint inhibitor. Adcetris® (Brentuximab Vedotin) is an antibody drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. Seattle Genetics and Takeda are jointly developing Adcetris®. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize Adcetris in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for Adcetris® on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs. Adcetris has received marketing authorization by regulatory authorities in more than 45 countries. In addition, Adcetris® is being evaluated as an investigational agent in more than 30 ongoing clinical trials, including four phase 3 studies, across a variety of CD30-expressing malignances including HL. Opdivo® (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. The FDA approved Opdivo® (nivolumab) injection, for intravenous use for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Disease: relapsed or refractory Hodgkin lymphoma, relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL)
Details: • On January 12, 2015, Seattle Genetics and BMS announced that the companies have entered into a clinical trial collaboration agreement to evaluate the investigational combination of Seattle Genetics’ antibody-drug conjugate (ADC) Adcetris® (brentuximab vedotin) and BMS’ immunotherapy Opdivo® (nivolumab) in two planned Phase 1/2 clinical trials. The first trial will evaluate the combination of Adcetris® and Opdivo® as a potential treatment option for patients with relapsed or refractory Hodgkin lymphoma (HL), and the second trial will focus on patients with relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL). The studies are expected to begin in 2015, with Seattle Genetics conducting the HL trial and BMS conducting the NHL trial. Additional details of the collaboration were not disclosed.
Latest news: • On June 2, 2017, BMS and Seattle Genetics have entered into a collaboration agreement to evaluate the combination of Opdivo® and Adcetris® in a pivotal phase 3 clinical trial. The trial will evaluate the combination of Adcetris® and Opdivo® versus Adcetris® alone as a potential treatment option for patients with relapsed/refractory or transplant-ineligible advanced classical Hodgkin lymphoma. The planned phase 3 study will be a randomized, open-label global clinical trial in classical Hodgkin lymphoma patients with relapsed/refractory disease who are ineligible for autologous stem cell transplant (ASCT) or after failure of ASCT. The pivotal study is expected to begin in mid-2017.