Seattle Genetics Reports Data from Phase I Trial of ADCETRIS® (Brentuximab
Vedotin) in Front-line Mature T-Cell Lymphomas (MTCL)
-100 Percent Objective Response Rate, Including 88 Percent Complete
Remissions, in Newly Diagnosed MTCL Patients Treated with ADCETRIS in
Combination with CHP Chemotherapy-
-Data Support Planned Phase III Trial in Front-line MTCL, Including Systemic
Anaplastic Large Cell Lymphoma and Other Types of Peripheral T-cell Lymphomas-
ATLANTA -- December 09, 2012
Seattle Genetics, Inc. (Nasdaq: SGEN) today announced results from a phase I
clinical trial of ADCETRIS (brentuximab vedotin) in combination with
chemotherapy for the treatment of newly diagnosed mature T-cell lymphoma
(MTCL) patients, including patients with systemic anaplastic large cell
lymphoma (sALCL). The data were presented at the 54^th American Society of
Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012
in Atlanta, GA. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30.
ADCETRIS is not currently approved for use in the front-line treatment of
In the phase I trial, newly diagnosed patients received six cycles of ADCETRIS
every three weeks in combination with cyclophosphamide, doxorubicin and
prednisone (CHP). This regimen removes vincristine (Oncovin) from CHOP, the
standard treatment in this setting. Patients who achieved at least a partial
remission after completing six cycles of combination therapy were eligible to
receive continued single-agent ADCETRIS for up to ten additional 3-week
cycles. The primary endpoints of the trial included defining maximum tolerated
dose of ADCETRIS in combination with CHP and evaluating safety. The secondary
endpoints were investigator assessment of response, progression-free survival
and overall survival.
After completing combination therapy, 26 of 26 patients (100 percent) treated
with ADCETRIS plus CHP had an objective response, including 23 patients (88
percent) with a complete remission. All 23 patients who achieved a complete
remission demonstrated normalized glucose uptake by PET (positron emission
“The standard front-line regimen for patients with mature T-cell lymphomas is
a combination chemotherapy regimen, CHOP, that has demonstrated complete
remission rates of 39 to 53 percent, with a 5-year overall survival rate of
less than 50 percent,” said Michelle Fanale, M.D., Associate Professor in the
Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University
of Texas MD Anderson Cancer Center. “There is significant need to advance the
treatment paradigm for newly diagnosed patients with these aggressive types of
lymphoma. Data from this trial support further evaluation of ADCETRIS in the
front-line treatment of patients with mature T-cell lymphomas.”
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)
Data were reported from 26 previously untreated patients who received the
combination regimen of ADCETRIS plus CHP. Nineteen patients had sALCL, and
seven patients had a diagnosis of another mature T- or NK-cell lymphoma. The
median age of patients was 56 years. Key findings, which were highlighted in
an oral presentation by Dr. Fanale, include:
*All 26 patients (100 percent) achieved an objective response after either
completing six cycles of combination therapy or at the latest assessment
for three patients who discontinued treatment prior to cycle six.
Twenty-three patients (88 percent) achieved a complete remission and three
patients (12 percent) achieved a partial remission.
*Among 19 sALCL patients, 19 (100 percent) achieved an objective response,
including 16 (84 percent) with a complete remission.
*Among the seven non-sALCL patients, 100 percent achieved a complete
remission with combination therapy, including two patients with PTCL – not
otherwise specified (PTCL-NOS), two patients with angioimmunoblastic
T-cell lymphoma, two patients with adult T-cell leukemia/ lymphoma and one
patient with enteropathy-associated T-cell lymphoma.
*Median progression-free survival and median overall survival have not been
reached with a median follow-up of nine months.
*Patients received a median of six cycles of CHP plus ADCETRIS and a median
of six additional cycles of single-agent ADCETRIS.
*The maximum tolerated dose of ADCETRIS in combination with CHP was not
exceeded at 1.8 milligrams per kilogram (mg/kg).
*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.
“These data provide strong rationale for our planned phase III clinical trial
to evaluate ADCETRIS plus CHP compared to CHOP in front-line patients with
mature T-cell lymphomas,” said Clay B. Siegall, Ph.D., President and Chief
Executive Officer at Seattle Genetics. “We are encouraged by the potential to
introduce ADCETRIS into a novel regimen for these patients, with a goal of
redefining front-line therapy from the standard therapeutic approach that has
not seen an advance in decades.”
A phase III clinical trial of ADCETRIS in CD30-positive MTCL patients is
planned to compare progression-free survival in patients receiving ADCETRIS in
combination with CHP (A+CHP) to patients receiving CHOP alone. The trial is
expected to begin by late 2012 or early 2013.
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 PTCL,
angioimmunoblastic T-cell lymphomaand adult T-cell lymphoma.
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 FDA granted accelerated approval of ADCETRIS in August 2011 for
two indications. ADCETRIS is being developed in collaboration with Millennium:
The Takeda Oncology Company. In addition, Seattle Genetics has three other
clinical-stage 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 in
the featured indication. 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 future clinical trials studying such indication and the risk of
adverse events as ADCETRIS advances in such 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 otherwise.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160 (Investors)
Tricia Larson, 425-527-4180 (Media)
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