Clinical Trials

Date: 2015-12-23

Type of information: Initiation of the trial

phase: 1-2a

Announcement: initiation of the trial

Company: Seattle Genetics (USA - WA) BMS (USA - NY)

Product: Adcetris® (brentuximab vedotin) and Opdivo® (nivolumab)

Action mechanism:

• monoclonal antibody/antibody drug conjugate (ADC)/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.
• In December 2014, 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 CD30-expressing non-Hogkin lymphoma

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On December 23, 2015, Seattle Genetics and BMS announced that the companies have initiated a phase 1/2 clinical trial of Adcetris® (brentuximab vedotin) in combination with Opdivo® (nivolumab) for patients with CD30-expressing relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).
• The phase 1/2 open-label, multi-center, clinical trial is designed to evaluate the safety, tolerability and antitumor activity of Adcetris® in combination with Opdivo in patients with relapsed or refractory CD30-expressing NHL. The study will consist of a phase 1 dose evaluation portion followed by a single-arm phase 2 portion that will expand enrollment to treat disease-specific cohorts with relapsed or refractory DLBCL, PTCL or CTCL at the recommended dose level and treatment schedule. The primary endpoints are safety, tolerability and objective response rate of the combination of Adcetris® with Opdivo. The secondary endpoints include duration of response, complete response rate with the combination regimen, duration of complete response, progression-free survival and overall survival. The trial is being conducted at multiple centers in the United States, Canada and Europe and is designed to enroll approximately 120 patients.
• This is the second of two trials being conducted under a previously announced clinical trial collaboration agreement between BMS and Seattle Genetics. The other trial has been initiated in October 2015 in patients with relapsed or refractory Hodgkin lymphoma after failure of frontline treatment.
• The study is a part of a broad development program that includes more than 70 ongoing clinical trials evaluating Adcetris® in multiple lines of therapy for Hodgkin and non-Hodgkin lymphoma and as part of novel combinations that could result in improved clinical benefit with manageable safety profiles.

Is general: Yes