-Phase III Trial Planned in Front-line Mature T-Cell Lymphomas-
SAN FRANCISCO--(BUSINESS WIRE)--Jan. 26, 2012--
Seattle Genetics, Inc. (Nasdaq:SGEN) and Millennium: The Takeda Oncology
Company today announced interim results from 32 patients treated to date
in a phase I clinical trial of ADCETRIS (brentuximab vedotin)
administered in combination with or sequentially with chemotherapy for
the treatment of newly diagnosed systemic anaplastic large cell lymphoma
(sALCL) and other CD30-positive mature T-cell lymphoma patients. The
data are being presented at the T-Cell Lymphoma Forum being held January
26-28, 2012 in San Francisco, CA. ADCETRIS is not approved for use in
front-line mature T-cell lymphoma.
In the phase I trial, newly diagnosed patients are enrolled to one of
two regimens evaluating ADCETRIS administered either sequentially with
CHOP(1) or concurrently with CH-P, which removes vincristine
from the regimen:
The sequential treatment regimen comprises two cycles of single-agent
ADCETRIS every three weeks at 1.8 milligrams per kilogram (mg/kg)
followed by six cycles of CHOP. Patients who achieve at least a
partial remission (PR) after completing the six cycles of CHOP are
eligible to receive continued single-agent ADCETRIS at 1.8 mg/kg for
up to an additional eight 3-week cycles.
The concurrent treatment regimen comprises six cycles of ADCETRIS
every three weeks in combination with CH-P. Patients who achieve at
least a PR after completing the six cycles of combination therapy are
eligible to receive continued single-agent ADCETRIS for up to an
additional ten 3-week cycles.
Data were reported from 32 previously untreated patients, including 12
who received the sequential regimen and 20 who received the concurrent
regimen. Thirty patients had sALCL, one patient had peripheral T-cell
lymphoma-not otherwise specified (PTCL-NOS) and one patient had human
T-cell lymphotropic virus (HTLV)-1 associated T-cell lymphoma. Key
findings, which will be presented by Dr. Michelle Fanale from The
University of Texas MD Anderson Cancer Center, include:
The recommended dose of ADCETRIS in combination with CH-P is 1.8 mg/kg
every three weeks.
Across all regimens, the most common adverse events regardless of
severity or relationship to study drug were nausea (38 percent),
fatigue (25 percent) and peripheral sensory neuropathy (25 percent).
Grade 3 or higher adverse events regardless of relationship to study
drug were anemia (6 percent), fatigue (6 percent), peripheral edema (6
percent) and white blood cell count decrease (6 percent).
All 12 patients (100 percent) treated with the sequential regimen
achieved an objective response after two cycles of single-agent
ADCETRIS, including four patients (33 percent) with a complete
remission (CR) and eight patients (67 percent) with a PR. All 12
evaluable patients had sALCL. At the time of data analysis, six of
these 12 patients had completed six subsequent cycles of CHOP and were
evaluable for response. Of these six evaluable patients, four patients
(67 percent) achieved a CR and two patients (33 percent) achieved a
PR. Five remaining patients were not yet evaluable for response. One
patient discontinued treatment during CHOP chemotherapy due to
progressive disease, after achieving a PR with two cycles of ADCETRIS.
Among 20 patients treated with the concurrent regimen, all five
patients (100 percent) who had completed the full course of six cycles
of multi-agent induction treatment and were evaluable for response at
the time of data analysis achieved a CR. All five evaluable patients
had sALCL. The remaining 15 patients were not yet evaluable for
“The front-line regimen for aggressive T-cell lymphomas, including
systemic ALCL, has not been improved upon since CHOP was introduced
decades ago, and more than half of these patients will relapse,” said
Dr. Michelle Fanale, Assistant Professor in the Department of
Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas
MD Anderson Cancer Center. “The interim data from this phase I clinical
trial suggest that ADCETRIS has the potential to play an important role
in advancing the treatment of newly diagnosed T-cell lymphoma patients,
and continued investigation of ADCETRIS in these patients is warranted.”
The primary endpoints of the trial are dose-limiting toxicities, safety
and tolerability of ADCETRIS when combined or used sequentially with
multi-agent front-line chemotherapy regimens. The secondary endpoints
are investigator assessment of response, progression-free survival (PFS)
and overall survival (OS). The original clinical trial protocol included
only sALCL patients, but was recently expanded to include patients with
other subtypes of CD30-positive mature T- and NK-cell lymphomas. The
median age of patients across all treatment arms was 58 years.
Enrollment is ongoing in this phase I, open-label, multi-center trial.
A phase III clinical trial of ADCETRIS in CD30-positive mature T-cell
lymphoma patients, including sALCL, is planned to compare PFS in
patients receiving ADCETRIS in combination with CH-P to patients
receiving CHOP alone.
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.
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.
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
ADCETRIS is not approved for use outside the United States. The
marketing authorization application for ADCETRIS in relapsed or
refractory Hodgkin lymphoma and systemic ALCL, filed by Takeda Global
Research & Development Centre (Europe), was accepted by the European
Medicines Agency for review in June 2011.
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, Bayer, Celldex Therapeutics, Daiichi
Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as
well as ADC co-development agreements with Agensys, an affiliate of
Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
The Takeda Oncology Company , a leading biopharmaceutical company
based in Cambridge, Mass., markets a first-in-class proteasome inhibitor
in the US, and has a robust clinical development pipeline of global
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 and Takeda are available through
their respective websites, http://www.millennium.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
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.
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
For Seattle Genetics:
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
featured clinical trials 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, 2011 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.
1) CHOP: cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin
(vincristine) and prednisone
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Source: Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160