Seattle Genetics Announces Data Presentations at ASCO Related to ADCETRIS in AETHERA Post-Transplant Consolidation Setting

Seattle Genetics, Inc.

today announced several ADCETRIS (brentuximab vedotin) data presentations in the AETHERA post-transplant consolidation setting for Hodgkin lymphoma (HL) and in frontline diffuse large B-cell lymphoma (DLBCL) at the American Society of Clinical Oncology (ASCO) 50th Annual Meeting being held May 29 to June 2, 2015, in Chicago, IL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL) and several other types of non-Hodgkin lymphoma. "The ADCETRIS data presentations at the ASCO Annual Meeting in both Hodgkin and non-Hodgkin disease settings continue to support our vision to establish ADCETRIS as the foundation of therapy for CD30-expressing diseases," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "The data analyses presented from the AETHERA trial show the potential benefits to high risk HL patients of using ADCETRIS immediately following an autologous stem cell transplant to prevent progression. In non-Hodgkin lymphoma, the interim data presented in our phase 2 frontline DLBCL clinical trial evaluating ADCETRIS in combination with standard of care show encouraging activity, particularly in patients with CD30-positive disease, and we look forward to evaluating ADCETRIS further in both frontline and relapsed/refractory DLBCL." Multivariate analysis of PFS from the AETHERA trial: A phase 3 study of brentuximab vedotin consolidation after autologous stem cell transplant for HL (Abstract #8519, poster presentation Sunday, May 31, 2015) Data were reported from a multivariate analysis of the effects of demographics, baseline disease characteristics and other risk factors on progression-free survival (PFS) from the phase 3 AETHERA clinical trial. After adjusting for several clinical factors in a multivariate regression analysis, consolidation treatment with ADCETRIS was significantly associated with improved PFS compared with placebo (hazard ratio of 0.44) and was more important, or as important, as all evaluated clinical factors. Results show consistent PFS benefit of ADCETRIS consolidation therapy, regardless of the clinical factors, further supporting ADCETRIS use as consolidation in HL patients following autologous stem cell transplant (ASCT). ADCETRIS is currently not approved for use in the AETHERA treatment setting. Based on the positive results from the AETHERA trial, a supplemental Biologics License Application (BLA) for ADCETRIS in the AETHERA setting for the post-ASCT consolidation treatment of HL patients at high risk of relapse or progression was accepted for filing by the U.S. Food and Drug Administration (FDA). The FDA granted Priority Review for the application and the Prescription Drug User Fee Act (PDUFA) target action date is August 18, 2015. Updated results of a phase 2 trial of brentuximab vedotin combined with RCHOP in frontline treatment of pts with high-intermediate/high-risk DLBCL (Abstract #8506, oral presentation Monday, June 1, 2015, at 11:21 a.m. CT) Interim results were reported from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with the standard of care regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) in frontline high-intermediate or high-risk DLBCL. Patients were randomized to receive standard dose RCHOP with either 1.2 milligrams per kilogram (mg/kg) (30 patients) or 1.8 mg/kg (23 patients) of ADCETRIS. The trial was designed to assess antitumor activity and the safety profile of ADCETRIS plus RCHOP in these patients. Data were reported from 53 patients with a median age of 67 years. Nearly all (96 percent) had stage III/IV disease and were considered high-risk (38 percent) or high-intermediate risk (62 percent). Key findings presented by Dr. Nancy Bartlett from the Washington University, Siteman Cancer Center in St. Louis, MO, included: Of 51 evaluable patients across both dose cohorts, 41 patients (80 percent) obtained an objective response, including 34 patients (67 percent) with a complete remission and seven patients (14 percent) with a partial remission. Five patients (10 percent) had progressive disease. Five patients did not have end of treatment assessments. The estimated PFS rate at six months was 79 percent and at 12 months was 65 percent. Antitumor activity was not significantly different between the two dosage arms. Of 25 evaluable patients who had CD30-positive disease, 21 patients (84 percent) obtained an objective response, including 19 patients (76 percent) with a complete remission and two patients (eight percent) with a partial remission. The estimated PFS rate for CD30-positive patients at both six and 12 months was 86 percent. Of 23 evaluable patients who had CD30-undetectable disease, 19 patients (83 percent) obtained an objective response, including 14 patients (61 percent) with a complete remission and five patients (22 percent) with a partial remission. The estimated PFS rate for CD30-undetectable patients at six months was 81 percent and at 12 months was 58 percent. These data demonstrate that among CD30-positive DLBCL patients, the complete remission rate was higher (76 versus 61 percent) and the estimated PFS at 12 months was higher (86 versus 58 percent) compared to patients with undetectable CD30 by immunohistochemistry testing. The most common treatment-emergent adverse events of any grade for patients treated in the 1.2 mg/kg and 1.8 mg/kg combination cohorts, respectively, were fatigue (55 and 68 percent), peripheral sensory neuropathy (55 and 69 percent), nausea (45 and 68 percent), diarrhea (48 and 60 percent) and vomiting (24 and 55 percent). The most common Grade 3 or 4 treatment-emergent adverse events for patients treated in the 1.2 mg/kg and 1.8 mg/kg combination cohorts were neutropenia, febrile neutropenia and anemia. The phase 2 trial is ongoing and was recently expanded to explore the activity and safety of ADCETRIS plus RCHP (omitting vincristine) as a frontline treatment in patients with CD30-positive, high-intermediate or high-risk DLBCL. Separately, ADCETRIS is being evaluated in relapsed or refractory DLBCL. For more information about these trials, visit www.clinicaltrials.gov. ADCETRIS is currently not approved for the treatment of DLBCL.