-Encouraging Data from Single-Agent Trial in Relapsed DLBCL Support
Further Evaluation of ADCETRIS in the Frontline DLBCL Setting-
BOTHELL, Wash.--(BUSINESS WIRE)--Aug. 15, 2013--
Genetics, Inc. (Nasdaq:SGEN) today announced the initiation of a
phase 2 clinical trial evaluating ADCETRIS (brentuximab vedotin) in
combination with RCHOP (A+RCHOP), the current standard frontline
therapy, for newly diagnosed patients with diffuse large B-cell lymphoma
(DLBCL). The study is intended to evaluate the complete remission rate
and safety of the A+RCHOP regimen. ADCETRIS is an antibody-drug
conjugate (ADC) directed to CD30. ADCETRIS is currently not approved for
the treatment of DLBCL.
“The encouraging data we have observed in our phase 2 trial of ADCETRIS
in relapsed non-Hodgkin lymphoma, including DLBCL patients, support
evaluation in earlier lines of therapy for patients with this aggressive
lymphoma type,” said Clay B. Siegall., Ph.D., President and Chief
Executive Officer at Seattle Genetics. “This trial will provide us with
data on the tolerability of the combination, as well as the antitumor
activity achieved by adding ADCETRIS to the current standard frontline
regimen. In addition, based on interim findings from our trial in the
relapsed setting in which objective responses were observed among
patients with low or undetectable levels of CD30 by conventional
screening methods, we will enroll high-risk DLBCL patients to this
frontline trial without prescreening for CD30 expression.”
In this phase 2, open-label clinical trial, approximately 50 frontline
high-risk DLBCL patients will receive ADCETRIS in combination with the
standard of care consisting of rituximab, cyclophosphamide, doxorubicin,
vincristine and prednisone (A+RCHOP). Patients will be randomized to
receive standard dose RCHOP with either 1.2 milligrams per kilogram
(mg/kg) or 1.8 mg/kg of ADCETRIS. The trial will enroll patients
regardless of CD30 expression level by immunohistochemistry (IHC) to
further explore previously reported interim data from an ongoing phase 2
trial for relapsed B-cell lymphomas, including DLBCL, demonstrating
objective responses in patients with varying levels of CD30. The primary
endpoints are to assess the complete remission rate and safety profile
of the combination. Secondary endpoints include objective response rate,
progression-free survival and overall survival.
At the International Conference on Malignant Lymphoma in June 2013, data
were presented from an ongoing phase 2 trial for relapsed B-cell
lymphomas that included 44 relapsed patients who received single-agent
ADCETRIS, including 25 with DLBCL. Among DLBCL patients, the objective
response rate was 44 percent (11 of 25), including 20 percent complete
remissions and 24 percent partial remissions. Eighty-one percent of
patients achieved tumor reduction. Among 44 B-cell lymphoma patients
enrolled, the most common treatment-emergent adverse events were
neutropenia (43 percent), fatigue (36 percent), nausea (34 percent) and
diarrhea (32 percent). The most common Grade 3 or 4 adverse events were
neutropenia (25 percent Grade 3; 11 percent Grade 4) and anemia (9
percent Grade 3).
More information about the ongoing phase 2 frontline or relapsed DLBCL
trials, including enrolling centers, is available by visiting www.clinicaltrials.gov.
About Diffuse Large B-Cell Lymphoma
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 lymphoma (NHL) represents
a diverse group of cancers that develop in the lymphatic system and are
characterized by uncontrolled growth and accumulation of abnormal
lymphocytes. Lymphocytes are a type of white blood cells that are
responsible for defending the body against infection. The most common
forms of NHL are follicular (slow growth) and diffuse large B-cell
lymphoma (a faster growing sub-type).
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 FDA in August 2011 and
approval with conditions by Health Canada in February 2013 for two
indications: (1) the treatment of patients with HL 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 sALCL. See important safety information below.
ADCETRIS is being evaluated in more than 20 ongoing clinical trials
across both corporate and investigator-sponsored studies. The trials are
designed to broadly evaluate the potential of ADCETRIS in earlier lines
of its approved indications as well as in many additional types of
CD30-positive malignancies, including cutaneous T-cell lymphoma (CTCL),
B-cell lymphomas and mature T-cell lymphomas (MTCL). For more
information, visit www.clinicaltrials.gov.
The clinical trials include:
ALCANZA, a phase 3 trial in relapsed CD30-positive CTCL
ECHELON-1, a phase 3 frontline trial in HL
ECHELON-2, a phase 3 frontline trial in MTCL
Phase 2 trial for relapsed or refractory CD30-positive non-Hodgkin
Phase 2 trial for frontline HL in patients age 60 and older
Phase 2 trial for CD30-positive non-lymphoma malignancies
Phase 1 / 2 trial in combination with bendamustine for first relapse HL
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 company’s lead program, ADCETRIS®
(brentuximab vedotin), received accelerated approval from the U.S. Food
and Drug Administration in August 2011 and approval with conditions from
Health Canada in February 2013 for two indications. In addition, under a
collaboration with Millennium: The Takeda Oncology Company, ADCETRIS
received conditional approval from the European Commission in October
2012. Seattle Genetics is also advancing a robust pipeline of
clinical-stage ADC programs: SGN-75, ASG-22ME, SGN-CD19A, SGN-CD33A,
ASG-15ME and SGN-LIV1A. Seattle Genetics has collaborations for its ADC
technology with a number of leading biotechnology and pharmaceutical
companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer,
Celldex, 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 in treating patients with DLBCL. 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 this
clinical trial for DLBCL and the risk of adverse events as ADCETRIS
advances in this and other 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 June 30, 2013 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