Seattle Genetics and Millennium Initiate Global Phase III Clinical Trial of
ADCETRIS® (Brentuximab Vedotin) in Front-line CD30-Expressing Mature T-Cell
− Phase III Clinical Trial Designed to Examine the Use of ADCETRIS as Part of
a Front-line Treatment Regimen for Newly Diagnosed MTCL Patients, Including
Systemic Anaplastic Large Cell Lymphoma and Other Types of Peripheral T-cell
BOTHELL, Wash. & CAMBRIDGE, Mass. -- January 24, 2013
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. The abstract can be found at www.hematology.org.
More information about the ECHELON-2 phase III trial of ADCETRIS in front-line
CD30-expressing MTCL, including enrolling centers, will be available by
ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal
antibody attached by a protease-cleavable linker to a microtubule disrupting
agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary
technology. The ADC employs a linker system that is designed to be stable in
the bloodstream but to release MMAE upon internalization into CD30-expressing
ADCETRIS was granted accelerated approval by the U.S. Food and Drug
Administration (FDA) in August 2011 for two indications: (1) the treatment of
patients with Hodgkin lymphoma after failure of autologous stem cell
transplant (ASCT) or after failure of at least two prior multi-agent
chemotherapy regimens in patients who are not ASCT candidates, and (2) the
treatment of patients with sALCL after failure of at least one prior
multi-agent chemotherapy regimen. The indications for ADCETRIS are based on
response rate. There are no data available demonstrating improvement in
patient-reported outcomes or survival with ADCETRIS. ADCETRIS has not been
approved for use in any front-line setting.
ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for the treatment of adult patients with relapsed
or refractory CD30+ Hodgkin lymphoma (HL): (1) following autologous stem cell
transplant (ASCT), or (2) following at least two prior therapies when ASCT or
multi-agent chemotherapy is not a treatment option. ADCETRIS is indicated for
the treatment of adult patients with relapsed or refractory systemic
anaplastic large cell lymphoma (sALCL). See important safety information
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the
terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian
commercialization rights and the Takeda Group has rights to commercialize
ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are
funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan
where the Takeda Group is solely responsible for development costs.
About T-Cell Lymphomas
Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma
and non-Hodgkin lymphoma. Non-Hodgkin lymphomas are broadly divided into two
major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and
T-cell lymphomas, which develop from abnormal T-lymphocytes. The World Health
Organization identifies 22 subtypes of mature T- and NK-cell neoplasms,
including systemic ALCL which is an aggressive type of T-cell non-Hodgkin
lymphoma that expresses CD30. Other mature T-cell lymphomas include peripheral
T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphomaand adult T-cell
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company
based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome
inhibitor, and has a robust clinical development pipeline of product
candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda
Pharmaceutical Company Ltd. in May, 2008. The Company’s research, development
and commercialization activities are focused in oncology. Additional
information about Millennium is available through its website,
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and
commercialization of monoclonal antibody-based therapies for the treatment of
cancer. The company’s lead program, ADCETRIS, received accelerated approval
from the U.S. Food and Drug Administration in August 2011 for two indications.
In addition, under a collaboration with Millennium: The Takeda Oncology
Company, ADCETRIS received conditional approval from the European Commission
in October 2012. Seattle Genetics also has three other clinical-stage
antibody-drug conjugate (ADC) programs: SGN-75, ASG-5ME and ASG-22ME. Seattle
Genetics has collaborations for its ADC technology with a number of leading
biotechnology and pharmaceutical companies, including Abbott, Agensys (an
affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo,
Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC
co-development agreements with Agensys and Genmab. More information can be
found at www.seattlegenetics.com.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting
in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary
Warnings and Precautions:
*Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy
that is predominantly sensory. Cases of peripheral motor neuropathy have
also been reported. ADCETRIS-induced peripheral neuropathy is cumulative.
Treating physicians should monitor patients for symptoms of neuropathy,
such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
sensation, neuropathic pain or weakness and institute dose modifications
*Infusion reactions: Infusion-related reactions, including anaphylaxis,
have occurred with ADCETRIS. Monitor patients during infusion. If an
infusion reaction occurs, the infusion should be interrupted and
appropriate medical management instituted. If anaphylaxis occurs, the
infusion should be immediately and permanently discontinued and
appropriate medical management instituted.
*Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS
and consider more frequent monitoring for patients with Grade 3 or 4
neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays,
reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can
occur with ADCETRIS.
*Tumor lysis syndrome: Patients with rapidly proliferating tumor and high
tumor burden are at risk of tumor lysis syndrome and these patients should
be monitored closely and appropriate measures taken.
*Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death has been reported in ADCETRIS-treated patients.
In addition to ADCETRIS therapy, other possible contributory factors
include prior therapies and underlying disease that may cause
immunosuppression. Consider the diagnosis of PML in any patient presenting
with new-onset signs and symptoms of central nervous system abnormalities.
Evaluation of PML includes, but is not limited to, consultation with a
neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS
if PML is suspected and discontinue ADCETRIS if PML is confirmed.
*Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with
ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and
administer appropriate medical therapy.
*Use in pregnancy: Fetal harm can occur. Pregnant women should be advised
of the potential hazard to the fetus.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials.
Across both trials, the most common adverse reactions (≥20%), regardless of
causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea,
anemia, upper respiratory tract infection, diarrhea, pyrexia, rash,
thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with
ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please
see the full U.S. prescribing information for ADCETRIS at
www.seattlegenetics.com or www.ADCETRIS.com.
Certain of the statements made in this press release are forward-looking, such
as those, among others, relating to the therapeutic potential of ADCETRIS and
initiation of future clinical trials. Actual results or developments may
differ materially from those projected or implied in these forward-looking
statements. Factors that may cause such a difference include the inability to
show sufficient activity in the phase III trial and the risk of adverse events
as ADCETRIS advances in clinical trials. In addition, data from our clinical
trials, including our pivotal trials which were the basis for FDA accelerated
approval, may not necessarily be indicative of subsequent clinical trial
results. More information about the risks and uncertainties faced by Seattle
Genetics is contained in the company’s 10-Q for the quarter ended September
30, 2012 filed with the Securities and Exchange Commission. Seattle Genetics
disclaims any intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or
Peggy Pinkston, +1-425-527-4160
Tricia Larson, +1-425-527-4180
Lindsay Treadway, +1-617-444-3383
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