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:
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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)
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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
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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
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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
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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:
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Monday, October 1; 11:15 - 11:30 AM Central European Time (CET)
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Abstract #1063O
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Oral presentation in Hall K
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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:
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Peripheral blood stem cell (PBSC) mobilization and engraftment after
brentuximab vedotin treatment in anaplastic large cell lymphoma
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Sunday, September 30; 1:00 - 2:00 PM CET
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Abstract #1083P
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Hall XL
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First author: Andrei Shustov, M.D., University of Washington School of
Medicine
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