Seattle Genetics Offers Updated Progression-Free Survival, Overall Survival Data from ADCETRIS Frontline PTCL Phase 1 Trial

Seattle Genetics, Inc.

today highlighted ADCETRIS (brentuximab vedotin) data to be presented at the 2014 European Society for Medical Oncology (ESMO) Congress being held September 26-30, 2014 in Madrid, Spain. The data include a two-year durability analysis from a phase 1 clinical trial of ADCETRIS in combination with chemotherapy for the treatment of newly diagnosed peripheral T-cell lymphoma (PTCL) patients, also known as mature T-cell lymphoma (MTCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). In the phase 1 trial, newly diagnosed patients received ADCETRIS sequentially with the standard treatment in this setting consisting of cyclophosphamide, doxorubicin, vincristine and prednisone (A+CHOP) or in combination with CHP (A+CHP; removing vincristine from CHOP). In the combination arm, patients received ADCETRIS and CHP every three weeks for six cycles. Patients who achieved at least a partial remission after completing six cycles of combination therapy were eligible to receive continued single-agent ADCETRIS for up to ten additional three-week cycles. The primary endpoints of the trial included defining maximum tolerated dose of ADCETRIS in combination with CHP and evaluating safety. Other endpoints included investigator assessment of response, progression-free survival (PFS) and overall survival (OS). “Peripheral T-cell lymphoma includes a particularly aggressive group of non-Hodgkin lymphomas with relatively few patients achieving long-term remissions, and initial treatment has not changed in decades, typically including a suboptimal regimen of anthracycline-based chemotherapy,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Maturing data from this phase 1 trial in patients who have advanced or high-risk disease characteristics demonstrate durable progression-free survival and overall survival rates, supporting our belief that this novel ADCETRIS-containing regimen has the potential to redefine the treatment of frontline PTCL. This hypothesis is being tested in our ongoing phase 3 clinical trial, called ECHELON-2.” As previously reported at the 2013 American Society of Hematology (ASH) annual meeting and published in the Journal of Clinical Oncology, after completing combination therapy in the phase 1 trial, 26 of 26 patients (100 percent) treated with ADCETRIS plus CHP had an objective response, including 23 patients (88 percent) with a complete remission. All 23 patients who achieved a complete remission demonstrated normalized glucose uptake by PET (positron emission tomography) evaluation. The data presentation at the ESMO Congress is an updated two-year durability analysis from the phase 1 trial. Brentuximab Vedotin in Combination with CHP in Patients with Newly-Diagnosed CD30+ Peripheral T-cell Lymphoma (PTCL): Two-year Follow-up (Abstract #944O, oral presentation on Monday, September 29, 2014 at 14:00 CEST) Data were reported from 26 patients who received the combination regimen of ADCETRIS plus CHP. The median age of patients was 56 years. Nineteen patients had sALCL, including 16 patients (62 percent) with anaplastic lymphoma kinase (ALK) negative disease, typically associated with a poor prognosis and median PFS of approximately 18 months with a five-year OS of less than 50 percent. Seven patients had a diagnosis of other types of PTCL. The majority of patients had advanced stage disease and/or were considered high risk. The data will be highlighted in an oral presentation by Dr. Michelle Fanale from The University of Texas MD Anderson Cancer Center. Updated key findings for ADCETRIS in combination with CHP, based on a median observation time of 27.1 months from first dose of therapy, included: * The estimated two-year PFS rate was 54 percent, with no patients receiving a consolidative stem cell transplant. There have been no progression events since the previous presentation at the ASH annual meeting in December 2013. * The estimated two-year OS rate was 80 percent. * The most common treatment-emergent adverse events of any grade occurring in more than 40 percent of patients were peripheral sensory neuropathy, nausea, fatigue, hair loss, diarrhea and shortness of breath. ADCETRIS is currently not approved as a frontline treatment for PTCL. Based on these results, a global phase 3 study called ECHELON-2 was initiated and is currently enrolling patients. The ECHELON-2 trial is a randomized, double-blind, placebo-controlled, multi-center trial designed to investigate A+CHP versus CHOP as frontline therapy in patients with CD30-positive PTCL. Approximately 300 patients (approximately 150 patients per treatment arm) will be randomized to receive A+CHP or CHOP every three weeks for six to eight cycles.