Takeda, Seattle Genetics announce preliminary data from brentuximab vedotin phase I study on sALCL

Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), and Seattle Genetics, Inc. (Nasdaq: SGEN), today announced preliminary data from one arm of a three arm phase I, open-label, multicenter study designed to determine the safety and activity of sequential and combination treatment approaches of brentuximab vedotin with CHOP or CH-P chemotherapy in newly diagnosed patients with CD30-positive mature T- and NK- cell lymphomas. Data were presented from one arm, which evaluates brentuximab vedotin in sequence with CHOP in patients with newly diagnosed systemic anaplastic large cell lymphoma (sALCL), a subtype of mature T- and NK cell lymphomas. The data were reported during an oral presentation at the ESMO 2012 Congress (European Society for Medical Oncology) being held September 28 - October 2, 2012 in Vienna, Austria.    

Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of sALCL. Data from the other arms of the study evaluating administration of brentuximab vedotin with CH-P are expected to be presented during 2012.

"The preliminary data from the sequential treatment arm of this phase I study show that side effects were manageable and there are also some encouraging data on activity," said Michelle Fanale, M.D., University of Texas MD Anderson Cancer Center, Houston, TX. "We look forward to reporting additional data from the combination arms of the study at an upcoming medical congress."

Sequential Therapy with Brentuximab Vedotin in Newly Diagnosed Patients with Systemic Anaplastic Large Cell Lymphoma

The oral presentation featured data from Arm 1 of the study, which evaluated treatment with 1.8 milligrams per kilogram of single-agent brentuximab vedotin for two cycles prior to six cycles of CHOP. Patients who achieved a complete remission (CR) or partial remission (PR) following CHOP were eligible to continue single-agent brentuximab vedotin for up to eight cycles. The primary endpoints for Arm 1 are safety and tolerability. The secondary endpoint is investigator assessment of response using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). The median age of enrolled patients was 62 years (range, 23-81). Among the 13 patients with newly diagnosed sALCL, ten had anaplastic lymphoma kinase (ALK)-negative disease and three had ALK-positive disease.

The companies plan to initiate a phase III clinical trial in patients with mature T-cell lymphomas evaluating brentuximab vedotin in combination with CH-P compared to CHOP in late 2012 to early 2013.

Data, presented by Dr. Fanale, included:

• The most common (≥30 percent of total patients) adverse events (AEs), regardless of severity, were nausea (77 percent), peripheral sensory neuropathy (77 percent), vomiting (54 percent), constipation (46 percent) and fatigue (46 percent)
• The most common (≥10 percent of total patient) AEs of Grade 3 or higher were anemia, constipation, fatigue, peripheral sensory neuropathy and febrile neutropenia, each occurring in 15 percent of patients
• Of the 13 evaluable patients on Arm 1 of the study, 100 percent achieved an objective response following the first two cycles of treatment with single-agent brentuximab vedotin, including five CRs and eight PRs
• After eight cycles of sequential therapy, including two cycles of brentuximab vedotin followed by six cycles of CHOP, 11 patients had an objective response, including eight CRs and three PRs
• Objective responses were generally maintained in patients treated with single-agent brentuximab vedotin following CHOP, including seven of nine evaluable patients with CRs at Cycle 12 and five of five evaluable patients with CRs at Cycle 16

Details of the oral presentation are as follows:

• Monday, October 1; 11:15 - 11:30 AM Central European Time (CET)
• Abstract #1063O
• Oral presentation in Hall K
• First author: Michelle Fanale, M.D., The University of Texas M. D. Anderson Cancer Center

Data on brentuximab vedotin was also described in the following poster session:

• Peripheral blood stem cell (PBSC) mobilization and engraftment after brentuximab vedotin treatment in anaplastic large cell lymphoma
• Sunday, September 30; 1:00 - 2:00 PM CET
• Abstract #1083P
• Hall XL
• First author: Andrei Shustov, M.D., University of Washington School of Medicine