Seattle Genetics Initiates Phase 2 Clinical Trial of ADCETRIS® (Brentuximab Vedotin) Combination Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Seattle Genetics, Inc. SGEN today announced the initiation of a randomized phase 2 clinical trial of Rituxan (rituximab) and bendamustine with or without ADCETRIS (brentuximab vedotin) in relapsed or refractory patients with CD30-expressing diffuse large B-cell lymphoma (DLBCL). The study is intended to evaluate the activity and safety of the combination regimen. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a protein found on the surface of certain types of cells. CD30 is expressed in several types of non-Hodgkin lymphoma, including at least 25 percent of patients with DLBCL. ADCETRIS is currently not approved for the treatment of DLBCL. "Diffuse large B-cell lymphoma, or DLBCL, is the most common type of aggressive non-Hodgkin lymphoma. DLBCL patients who relapse following initial treatment often receive salvage therapy sometimes followed by an autologous stem cell transplant, after which most patients will eventually relapse," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "This trial is designed to build on the single-agent activity we have observed with ADCETRIS in CD30-expressing DLBCL, including both relapsed and refractory status. Our goal is to improve long-term outcomes for relapsed and refractory DLBCL patients who express CD30 at detectable levels by combining ADCETRIS with Rituxan and bendamustine, two agents that are commonly used in this disease setting." In this phase 2 randomized, open-label, multi-center clinical trial, approximately 110 relapsed/refractory CD30-expressing DLBCL patients will receive Rituxan and bendamustine either with or without ADCETRIS every three weeks for six cycles. Patients in the ADCETRIS combination arm who respond to treatment with a manageable safety profile may continue to receive single-agent ADCETRIS treatment for up to 10 additional cycles. The primary endpoint is to compare the objective response rates between the two study arms. Secondary endpoints include progression-free survival, complete remission rate, duration of response and overall survival. The study is being conducted at approximately 50 sites across North America and Europe. At the 2015 International Conference on Malignant Lymphoma (ICML), data were presented from an ongoing phase 2 trial for relapsed/refractory CD30-positive non-Hodgkin lymphoma that included DLBCL patients who received single-agent ADCETRIS or in combination with Rituxan every three weeks. Of the 48 patients treated in the single-agent arm, the objective response rate was 44 percent, including 19 percent complete remissions and 25 percent partial remissions. Of the 13 patients treated in the combination arm, the objective response rate was 46 percent, including 15 percent complete remissions and 31 percent partial remissions. The most common treatment-emergent adverse events of any grade occurring in more than 15 percent of all patients enrolled were fatigue, nausea, neutropenia, diarrhea, peripheral sensory neuropathy, fever and vomiting. The most common treatment-emergent adverse event Grade 3 or higher was neutropenia. Seattle Genetics is also evaluating ADCETRIS in newly diagnosed DLBCL patients through an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with RCHP (rituximab, cyclophosphamide, doxorubicin and prednisone). For more information about the DLBCL clinical trials, including enrolling centers, visit www.clinicaltrials.gov.