Seattle Genetics Reports Data from Phase I Trial of ADCETRIS® (Brentuximab
Vedotin) in Front-line Hodgkin Lymphoma at ASH Annual Meeting
- 96 Percent Complete Remission Rate in Newly Diagnosed Hodgkin Lymphoma
Patients Treated with ADCETRIS in Combination with AVD Chemotherapy -
- Safety and Response Data Support Ongoing Phase III Trial of ADCETRIS and AVD
Chemotherapy in Patients with Newly Diagnosed Hodgkin Lymphoma -
54th American Society of Hematology (ASH) Annual Meeting and Exposition
ATLANTA -- December 10, 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 advanced stage Hodgkin
lymphoma (HL) patients. The data were presented at the 54^th 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, a defining marker of classical HL. ADCETRIS is currently not approved
for use in the front-line treatment of HL.
In the phase I trial, newly diagnosed patients received ADCETRIS concomitantly
with either ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or AVD,
which removes bleomycin from the regimen. At the end of front-line therapy, 24
of 25 patients (96 percent) treated with ADCETRIS plus AVD and 21 of 22 (95
percent) patients treated with ADCETRIS plus ABVD had a complete remission.
None of the patients treated in the ADCETRIS plus AVD cohort experienced
pulmonary toxicity, compared with an expected rate of pulmonary toxicity
caused by ABVD alone of 10-25 percent. The trial was designed to establish the
safety profile and maximum tolerated dose when adding ADCETRIS to ABVD or AVD.
Antitumor activity was assessed as a secondary endpoint.
"For over 30 years, the standard of care for front-line HL has been a
chemotherapy regimen called ABVD that has demonstrated a complete remission
rate of 70 to 80 percent and is associated with considerable life-threatening
toxicities. There is a significant need to identify better treatment options
for patients in the front-line HL setting,” said Clay B. Siegall, Ph.D.,
President and Chief Executive Officer of Seattle Genetics. "Our goal is to
redefine front-line treatment of HL with the addition of ADCETRIS, and the
encouraging results of this phase I trial clearly support this goal and
provide rationale for the ongoing ADCETRIS phase III trial in this setting."
Front-line Therapy with Brentuximab Vedotin Combined with ABVD or AVD in
Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma (Abstract #798)
In this open-label, multicenter trial, cohorts of patients received an
escalating dose of ADCETRIS (0.6 milligrams per kilogram (mg/kg), 0.9 mg/kg,
1.2 mg/kg) every two weeks concomitantly with ABVD or a dose of 1.2 mg/kg
every two weeks concomitantly with AVD.
Fifty-one patients were enrolled in the phase I study and 47 were evaluable
for response at trial completion. The 47 evaluable patients included 25 in the
ADCETRIS plus AVD cohort and 22 in the ADCETRIS plus ABVD cohorts. All
patients were previously untreated and 45 percent had Stage IV HL. The median
age of patients across all cohorts of the trial was 33 years. Key findings,
which were highlighted in an oral presentation by Dr. Stephen Ansell,
Professor of Medicine, Division of Hematology, from the Mayo Clinic, included:
*Among the 25 evaluable patients in the ADCETRIS plus AVD cohort, 24
patients (96 percent) who completed front-line therapy on study achieved a
complete remission and one patient (four percent) experienced disease
*Among the 22 evaluable patients in the ADCETRIS plus ABVD cohorts, 21
patients (95 percent) who completed front-line therapy on study achieved a
complete remission. One patient was not evaluable for response due to
*Of the 48 evaluable patients in both study arms, 24 out of 26 (92 percent)
in the AVD cohort and 22 out of 22 (100 percent) in the ABVD cohorts had
negative interim PET scans after Cycle 2 as assessed by central review.
*No dose-limiting toxicity was observed at the maximum planned dose of
ADCETRIS (1.2 mg/kg every two weeks).
*The most common adverse events noted in the ABVD and AVD cohorts,
respectively, were nausea (72 percent, 85 percent), neutropenia (80
percent, 77 percent), peripheral sensory neuropathy (72 percent, 73
percent), vomiting (60 percent, 42 percent) and fatigue (44 percent, 50
*Grade 3 or higher adverse events occurring in more than one patient
overall noted in the ABVD and AVD cohorts, respectively, were neutropenia
(80 percent, 77 percent), anemia (20 percent, 12 percent), febrile
neutropenia (20 percent, 8 percent) and pulmonary toxicity (24 percent, 0
percent). One patient experienced a Grade 3 peripheral neuropathy event.
*As previously reported in the interim analysis of this study, pulmonary
toxicity was seen in the ADCETRIS plus ABVD cohorts, resulting in a
contraindication for the concomitant administration of ADCETRIS and
bleomycin. No pulmonary toxicity was observed in the ADCETRIS plus AVD
cohort. In the ADCETRIS plus ABVD cohorts, 11 out of 25 patients (44
percent) had a pulmonary toxicity event, and events were resolved in nine
of 11 patients (82 percent).
“For decades researchers have strived to improve our front-line HL treatment
strategy by enhancing the activity of traditional chemotherapy regimens while
reducing the significant toxicities and long-term side effects of such
regimens,” said Stephen Ansell,M.D., Ph.D., Professor of Medicine, Division
of Hematology, Mayo Clinic. “There is a significant need to identify better
treatment options for patients in the front-line setting. With a complete
response rate of 96 percent and a manageable safety profile, data from this
trial support further evaluation of ADCETRIS administered concomitantly with
AVD in previously untreated HL patients to potentially improve the current
standard of care.”
Seattle Genetics and Millennium: The Takeda Oncology Company have initiated a
phase III clinical trial in advanced stage front-line HL patients. The
randomized trial is comparing progression-free survival in patients receiving
ADCETRIS in combination with AVD to patients receiving ABVD alone. For more
information about the trial visit www.seattlegenetics.com or
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
ADCETRIS received accelerated approval from 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 systemic anaplastic large cell lymphoma (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
ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for the treatment of adult patients with relapsed
or refractory CD30+ 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 will be solely responsible for development costs.
About Hodgkin 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. Hodgkin lymphoma is distinguished from other types
of lymphoma by the presence of one characteristic type of cell, known as the
Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30.
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, 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 pulmonary
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
*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 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 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 phase III trial 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 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.
Seattle Genetics, Inc.
Peggy Pinkston, +1-425-527-4160
Tricia Larson, +1-425-527-4180
Press spacebar to pause and continue. Press esc to stop.