-34 Percent Objective Response Rate in Phase II Trial for Relapsed or
Refractory Non-Hodgkin Lymphomas, Including 44 Percent in Diffuse Large
B-cell Lymphoma (DLBCL)-
-Long-term Follow-up Demonstrates Durable Complete Remissions in
Pivotal Systemic ALCL Trial-
-Investigator Data Describe CD30 Expression in up to 25 Percent of
-Case Studies Indicate Activity of ADCETRIS in Systemic Mastocytosis-
ATLANTA--(BUSINESS WIRE)--Dec. 9, 2012--
Seattle Genetics, Inc. (Nasdaq: SGEN) today summarized ADCETRIS
(brentuximab vedotin) and CD30 expression data in non-Hodgkin lymphomas
and other malignancies from multiple presentations at the 54th
American Society of Hematology (ASH) Annual Meeting and Exposition being
held December 8-11, 2012 in Atlanta, GA. Highlights include encouraging
interim data from a phase II clinical trial of ADCETRIS in non-Hodgkin
lymphoma and long-term follow up from a pivotal clinical trial of
ADCETRIS in relapsed or refractory systemic anaplastic large cell
lymphoma (sALCL). In addition, investigators presented data describing
the expression of CD30 in DLBCL and case studies on ADCETRIS in patients
with systemic mastocytosis. ADCETRIS is an antibody-drug conjugate (ADC)
directed to CD30.
“This collection of data from both corporate studies as well as
investigator research into CD30 and the clinical role of ADCETRIS in
non-Hodgkin lymphomas add to a growing body of evidence that ADCETRIS
has potential in a broad array of CD30-positive malignancies,” said Clay
B. Siegall, Ph.D., President and Chief Executive Officer of Seattle
Genetics. “The numerous data sets at ASH also reinforce our development
strategy for the program and overall vision for ADCETRIS in the
treatment of patients with significant unmet medical needs.”
A Phase II Study of Brentuximab Vedotin in Patients with Relapsed or
Refractory CD30-Positive Non-Hodgkin Lymphomas (Abstract #2746)
In an ongoing phase II clinical trial, patients with relapsed or
refractory CD30-positive non-Hodgkin lymphomas have been enrolled,
including DLBCL and several other non-Hodgkin lymphoma subtypes. The
trial is designed to assess the antitumor activity, duration of response
and safety profile of ADCETRIS in these patients. At the time of data
analysis, 73 patients had been enrolled, including 44 with B-cell
lymphoma and 29 with T-cell lymphoma. The median number of prior
systemic therapies in both lymphoma classifications was two. Key
Of 64 patients evaluable for response, 22 patients (34 percent)
achieved an objective response, including 12 complete remissions and
ten partial remissions.
In B-cell lymphoma subtypes, 14 of 42 evaluable patients (33 percent)
achieved an objective response, including 11 of 25 DLBCL patients (44
In T-cell lymphoma subtypes, eight of 22 evaluable patients (36
percent) achieved an objective response, including five of ten
angioimmunoblastic T-cell lymphoma patients (50 percent).
The most common treatment-emergent adverse events of any grade were
fatigue (32 percent), neutropenia (26 percent), nausea (25 percent),
diarrhea (23 percent) and fever (22 percent).
The most common Grade 3 or 4 adverse event considered related to
ADCETRIS treatment was neutropenia (28 percent). Other Grade 3 or 4
adverse events occurring in two patients (three percent) each included
anemia, decreased appetite, hypotension and leukopenia.
Enrollment is ongoing. For more information about this trial, visit www.clinicaltrials.gov.
ADCETRIS is not approved for the treatment of the non-Hodgkin lymphoma
subtypes described in this presentation.
Long-term Remissions Observed in an Ongoing Phase II Study of
Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic
Anaplastic Large Cell Lymphoma (Abstract #2745)
A pivotal, single-arm clinical trial was conducted in 58 relapsed or
refractory sALCL patients to assess efficacy and safety of single-agent
ADCETRIS. In addition, the trial was designed to determine duration of
response, progression-free survival and overall survival. Enrolled
patients had received a median of two prior chemotherapy regimens.
Data highlights from long-term patient follow up in the pivotal trial
Median duration of response has not yet been reached for the 34
patients (59 percent) who achieved a complete remission on study, and
18 patients (53 percent) remained in continued complete remission at
the time of data analysis.
Estimated overall survival rate of patients at two years from
initiation of ADCETRIS treatment was 63 percent.
Patients who achieved a complete remission received a median of nine
doses of ADCETRIS.
The most common adverse events of any grade were peripheral neuropathy
(57 percent), nausea (40 percent), fatigue (38 percent), fever (34
percent) and diarrhea (29 percent).
The most common Grade 3 or 4 adverse events occurring in at least five
percent of patients included Grade 3 peripheral neuropathy (17
percent), Grade 3 neutropenia (12 percent) and Grade 4 neutropenia (9
percent). Other Grade 3 or 4 adverse events included thrombocytopenia
(14 percent) and anemia (7 percent).
CD30 Expression in Diffuse Large B-Cell Lymphoma (Abstract #1558) and
CD30 Expression in DLBCL and Its Relation to Important Clinical and
Biological Disease Features (Abstract #1592)
In two investigator-led abstracts, data described the outcome of
research into CD30 expression in DLBCL patient samples. In one
presentation, data indicated that 24.7 percent of DLBCL cases expressed
CD30 by immunohistochemistry (95 of 385 samples). In a separate
analysis, 23 percent of DLBCL cases expressed CD30 by
immunohistochemistry (34 of 148 samples). Both investigators concluded
that clinical evaluation of ADCETRIS in DLBCL is warranted.
These findings support Seattle Genetics’ ongoing evaluation of ADCETRIS
as a treatment for DLBCL. A phase II trial for non-Hodgkin lymphoma,
including DLBCL, is currently enrolling patients.
ADCETRIS is not approved for the treatment of the DLBCL.
Anti-CD30 Antibody-Drug Conjugate Brentuximab Vedotin May Be a
Promising Treatment Option for Systemic Mastocytosis (SM) (Abstract
Systemic mastocytosis is a clonal proliferation of abnormal mast cells
leading to clinical syndromes including aggressive systemic mastocytosis
(ASM) and mast cell leukemia. ASM has been shown to express CD30. In
this presentation, data describe the outcome of two patients with ASM
who had significant clinical benefit from treatment with ADCETRIS. Both
patients had a decrease in mast cell bone marrow percentage involvement
and density (including one partial remission), as well as improved
normal hematopoiesis. The investigator noted that treatment with
ADCETRIS was well-tolerated in these patients. ADCETRIS dose level was
reduced for one patient due to peripheral neuropathy and neutropenia.
ADCETRIS is not approved for the treatment of the systemic mastocytosis.
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 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 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
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
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, 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
Larson, (425) 527-4180