-70 percent objective response rate in retreatment trial-
-Multiple objective responses observed in CD30-positive non-Hodgkin
lymphoma patients, including four of seven patients with diffuse large
B-cell lymphoma-
-First report of CD30 expression from comprehensive screening in
broad range of non-lymphoma malignancies-
CHICAGO--(BUSINESS WIRE)--Jun. 2, 2012--
Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that data from
several clinical trials of ADCETRIS (brentuximab vedotin) will be
presented at the 2012 American Society of Clinical Oncology (ASCO)
Annual Meeting being held June 1-5, 2012 in Chicago, IL. Data
demonstrate the activity and tolerability when patients are retreated
with ADCETRIS, the activity and tolerability of ADCETRIS in
CD30-positive non-Hodgkin lymphomas and CD30 expression from a screening
protocol in non-lymphoma malignancies. ADCETRIS is an antibody-drug
conjugate (ADC) directed to CD30.
“Our goal is for ADCETRIS to become the foundation of therapy for
CD30-positive malignancies and, to that end, we are aggressively
investing in its clinical development and broadly exploring CD30
expression across numerous cancer types,” said Clay B. Siegall, Ph.D.,
President and Chief Executive Officer of Seattle Genetics. “Our data
presentations at ASCO highlight the potential for ADCETRIS and reinforce
our development strategy to generate data that will support stepwise
growth of ADCETRIS for patients with CD30-expressing malignancies.”
Retreatment with brentuximab vedotin in CD30-positive hematologic
malignancies: a phase II study (Abstract #8027)
In a phase II trial, patients who previously responded to treatment with
ADCETRIS, then discontinued treatment and subsequently had disease
progression or relapse were eligible for retreatment. Data were reported
from 24 patients treated to date on the study, including 16 with Hodgkin
lymphoma (HL) and eight with systemic anaplastic large cell lymphoma
(sALCL). Patients had received a median of four prior systemic
therapies, including ADCETRIS. Key findings include:
-
Of 23 evaluable patients, 70 percent (16 of 23) achieved an objective
response after retreatment with ADCETRIS, including nine complete
remissions (CRs) and seven partial remissions (PRs).
-
Median duration of retreatment objective response was 8.8 months.
-
Among retreated HL patients, nine of 16 (56 percent) achieved an
objective response. Among retreated sALCL patients, seven of eight (88
percent) achieved an objective response.
-
The most common adverse events were peripheral neuropathy (46
percent), nausea (42 percent), fatigue (38 percent), diarrhea (33
percent) and fever (29 percent).
-
The phase II retreatment trial is ongoing.
Details of the poster discussion presentation are as follows:
-
Saturday, June 2; 8:00 a.m. to 1:00 p.m. Central Time (CT), with
discussion from 12:00 p.m. to 1:00 p.m. CT
-
Poster display in room E450b and discussion in room E354a
-
First author: Dr. Nancy L. Bartlett, Washington University, Siteman
Cancer Center, St. Louis, MO
Brentuximab vedotin for relapsed or refractory non-Hodgkin lymphoma:
preliminary results from a phase II study (Abstract #8070)
In a phase II clinical trial, patients with relapsed or refractory
CD30-positive non-Hodgkin lymphomas, including diffuse large B-cell
lymphoma (DLBCL), peripheral T-cell lymphoma and other less common
lymphoma subtypes were enrolled. The trial was designed to assess the
antitumor activity, duration of response and safety profile of ADCETRIS
in these patients. At the time of data analysis, 28 patients had been
enrolled, including 18 with B-cell malignancies and ten with T-cell
malignancies. Across all patients, the median number of prior systemic
therapies was three. Key findings include:
-
Of 14 patients evaluable for response, five patients (36 percent)
achieved an objective response, including three CRs and two PRs.
-
Four of seven DLBCL patients treated with ADCETRIS achieved an
objective response, including two CRs and two PRs.
-
Seventy-one percent of patients achieved tumor reduction.
-
ADCETRIS treatment was generally well-tolerated, with the most common
adverse events being fatigue (21 percent), abdominal pain (17
percent), nausea (17 percent), chills (13 percent), diarrhea (13
percent) and vomiting (13 percent).
-
Enrollment is ongoing.
Details of the poster presentation are as follows:
-
Monday, June 4; 1:15 p.m. to 5:15 p.m. CT
-
Poster presentation in S Hall A2; poster board #35C
-
First author: Dr. Ranjana Advani, Stanford University Medical Center,
Stanford, CA
ADCETRIS is not approved for the treatment of the non-Hodgkin lymphoma
subtypes described in this presentation.
CD30 expression in non-lymphomatous malignancies (Abstract #3069)
In a screening study, assessment of CD30 expression was performed in
patients who had a non-lymphoma malignancy and were relapsed or
refractory to previous therapy, or had no alternative curative treatment
option available. Patients with CD30 expression were eligible for a
companion phase II clinical trial. Per the screening protocol, patients
were considered to be CD30-positive and eligible for the companion
clinical trial if at least 10 percent of malignant cells were positive
by immunohistochemistry or at least 20 percent of malignant cells were
positive by flow cytometry. At the time of data analysis, a total of
1,637 patients had been screened. Key findings include:
-
Thirty-eight patients (2 percent) and 17 different malignant diagnoses
were CD30 positive per protocol.
-
The most common malignancies with CD30 expression were mesothelioma (5
of 18 patients; 28 percent), melanoma (6 of 64 patients; 9 percent),
triple negative breast cancer (4 of 71 patients; 6 percent) and
ovarian carcinoma (9 of 173 patients; 5 percent).
-
Assessment of CD30 expression under the screening protocol is ongoing
with target enrollment of up to 3,000 patient tumor samples.
-
A phase II companion treatment protocol is ongoing to characterize the
antitumor activity of ADCETRIS in patients with CD30-positive
non-lymphoma malignancies and to correlate expression with activity.
Details of the poster presentation are as follows:
-
Monday, June 4; 8:00 a.m. to 12:00 p.m. CT
-
S Hall A2; poster board #16C
-
First author: Dr. Jeff P. Sharman, Willamette Valley Center Institute
and Research Center, Eugene, OR
ADCETRIS is not approved for the treatment of any non-lymphoma
malignancy.
For more information about the meeting, visit the ASCO annual meeting
website at www.asco.org.
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 received accelerated approval from the U.S. Food and Drug
Administration 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 systemic anaplastic large cell lymphoma (ALCL) 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 is not approved for use outside the United States. The
marketing authorization application for ADCETRIS in relapsed or
refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research &
Development Centre (Europe), was accepted for review by the European
Medicines Agency for review in June 2011.
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 will be solely
responsible for development costs.
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 U.S. Food and Drug Administration 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.
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 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 future
clinical trials 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 March
31, 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
ppinkston@seagen.com
