Millennium, Seattle Genetics commence ADCETRIS plus chemotherapy phase III trial in MTCL

Seattle Genetics, Inc. (Nasdaq: SGEN) and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), today announced the initiation of a global phase III clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the treatment of newly diagnosed CD30-positive mature T-cell lymphoma (MTCL) patients, including patients with systemic anaplastic large cell lymphoma (sALCL) and other types of peripheral T-cell lymphomas. The trial, also known as ECHELON-2, is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and also received scientific advice from the European Medicines Agency (EMA). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30. ADCETRIS is currently not approved for use in the front-line treatment of MTCL.

"The standard of care for newly diagnosed MTCL, a chemotherapy regimen called CHOP, has not changed in more than three decades, and there is a significant need to identify enhanced treatment options for these patients," said Clay B. Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics. "Recent phase I data from 26 patients presented at the ASH annual meeting showed that adding ADCETRIS to CHP resulted in compelling antitumor activity, with 100 percent of the patients experiencing a response, and a manageable safety profile. Our goal with this phase III trial is to redefine the standard of care for front-line treatment of MTCL."

"This is the third global phase III trial with ADCETRIS to be initiated in the past nine months," said Karen Ferrante, M.D., Chief Medical Officer, Millennium. "This trial represents another major achievement in our aspiration to bring important new therapies to patients with CD30-expressing malignancies by evaluating ADCETRIS in the front-line setting."

The ECHELON-2 study is a randomized, double-blind, placebo-controlled multi-center global phase III trial designed to investigate ADCETRIS in combination with cyclophosphamide, doxorubicin and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) as front-line therapy in patients with CD30-expressing MTCL. The primary endpoint is progression-free survival (PFS) per independent review facility assessment using the Revised Response Criteria for malignant lymphoma (Cheson, 2007). Secondary endpoints include overall survival (OS), complete remission (CR) rate and safety. The trial will be conducted in North America, Europe and Asia and is expected to enroll approximately 300 patients (approximately 150 patients per treatment arm). A molecular companion diagnostic test will be used in this trial to identify eligible patients based on CD30 expression. The companion diagnostic test is being developed under a previously announced collaboration agreement with Ventana Medical Systems, Inc. (Ventana), Millennium and Seattle Genetics.

At the recent 54^th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA, encouraging phase I data were presented from an abstract titled "Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Front-line Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas" (Abstract #60). The clinical trial was conducted to evaluate ADCETRIS in combination with chemotherapy for the treatment of newly diagnosed MTCL patients, including patients with sALCL. Data were reported from 26 previously untreated patients who received the combination regimen of ADCETRIS plus CHP.

After completing a combination regimen of ADCETRIS plus CHP, 26 of 26 patients (100 percent) treated with ADCETRIS plus CHP had an objective response, including 23 patients (88 percent) with a complete remission. The most common treatment-emergent adverse events of any grade regardless of relationship occurring in more than 30 percent of patients were nausea (62 percent), peripheral sensory neuropathy (62 percent), diarrhea (58 percent), fatigue (54 percent) and alopecia (46 percent). The most common Grade 3 or 4 treatment-emergent adverse events regardless of relationship included Grade 3 febrile neutropenia, peripheral sensory neuropathy, nausea and dyspnea and Grade 4 nausea and diarrhea.