-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--(BUSINESS WIRE)--Dec. 9, 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 54th
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 MTCL.
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 tomography) evaluation.
“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.
About ADCETRIS
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 tumor cells.
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 below.
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 lymphoma and 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
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to
pulmonary toxicity.
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 accordingly.
-
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.
Adverse Reactions:
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.
Drug Interactions:
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.
Source: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160 (Investors)
ppinkston@seagen.com
Tricia
Larson, 425-527-4180 (Media)
tlarson@seagen.com
